DilTIAZem (Lexi-Drugs)

Pronunciation

(dil TYE a zem)

Brand Names: US

Cardizem; Cardizem CD; Cardizem LA; Cartia XT; Dilt-XR; dilTIAZem CD [DSC]; Matzim LA; Taztia XT; Tiazac

Brand Names: Canada

ACT Diltiazem CD; ACT Diltiazem T; APO-Diltiaz; APO-Diltiaz CD; APO-Diltiaz SR [DSC]; APO-Diltiaz TZ; Cardizem CD; Diltiazem CD; Diltiazem TZ; Diltiazem-CD; MAR-Diltiazem T; NU-Diltiaz-SR [DSC]; Pharma-Diltiaz; PMS-Diltiazem CD; SANDOZ Diltiazem CD; SANDOZ Diltiazem T; TEVA-Diltazem; TEVA-Diltiazem CD; TEVA-Diltiazem HCl ER; Tiazac; Tiazac XC; TRIA-Diltiazem [DSC]

Dosing: Adult

Angina: Oral:

Capsule, extended release:

Dilt-XR: Initial: 120 mg once daily; titrate over 7 to 14 days; usual dose range (ACC/AHA [Gibbons 2003]): 120 to 320 mg daily: maximum: 480 mg/day.

Cardizem CD, Cartia XT: Initial: 120 to 180 mg once daily; titrate over 7 to 14 days; usual dose range (ACC/AHA [Gibbons 2003]): 120 to 320 mg daily; maximum: 480 mg/day.

Tiazac, Taztia XT: Initial: 120 to 180 mg once daily; titrate over 7 to 14 days; usual dose range (ACC/AHA [Gibbons 2003]): 120 to 320 mg daily; maximum: 540 mg/day.

Tablet, extended release (Cardizem LA, Matzim LA, Tiazac XC [Canadian product]): Initial: 180 mg once daily; may increase at 7- to 14-day intervals; usual dose range (ACC/AHA [Gibbons 2003]): 120 to 320 mg/day; maximum: 360 mg/day.

Tablet, immediate release (Cardizem): Initial: 30 mg 4 times daily; titrate dose gradually at 1- to 2-day intervals; usual dose range (ACC/AHA [Gibbons 2003]): 120 to 320 mg daily in 4 divided doses.

Hypertension: Oral:

Capsule, extended release (once-daily dosing):

Cardizem CD, Cartia XT: Initial: 180 to 240 mg once daily; dose adjustment may be made after 14 days; usual dose range: 120 to 360 mg once daily (ACC/AHA [Whelton 2017]); maximum: 480 mg/day

Dilt-XR: Initial: 180 to 240 mg once daily; dose adjustment may be made after 14 days; usual dose range: 120 to 360 mg once daily (ACC/AHA [Whelton 2017]); maximum: 540 mg/day

Tiazac, Taztia XT: Initial: 120 to 240 mg once daily; dose adjustment may be made after 14 days; usual dose range: 120 to 360 mg once daily (ACC/AHA [Whelton 2017]); maximum: 540 mg/day

Capsule, extended release (twice-daily dosing): Initial: 60 to 120 mg twice daily; dose adjustment may be made after 14 days; usual dose range: 120 to 180 mg twice daily

Note: Diltiazem is available as a generic intended for either once- or twice-daily dosing, depending on the formulation; verify appropriate extended release capsule formulation is administered.

Tablet, extended release (Cardizem LA, Matzim LA, Tiazac XC [Canadian product]): Initial: 180 to 240 mg once daily; dose adjustment may be made after 14 days; usual dose range: 120 to 360 mg once daily (ACC/AHA [Whelton 2017]); maximum: 540 mg/day

Idiopathic ventricular tachycardia (off-label use): Oral:

Immediate release: 60 mg 3 times daily (Gill 1992)

Extended release: 120 to 360 mg/day (AHA/ACC/HRS [Al-Khatib 2017]) in 1 to 2 divided doses

Atrial fibrillation, atrial flutter, PSVT (acute treatment): IV:

Control of rapid ventricular rate in atrial fibrillation or atrial flutter or conversion of PSVT:

Initial bolus dose: 0.25 mg/kg actual body weight over 2 minutes (average adult dose: 20 mg); ACLS guideline recommends 15 to 20 mg

Repeat bolus dose (may be administered after 15 minutes if the response is inadequate): 0.35 mg/kg actual body weight over 2 minutes (average adult dose: 25 mg); ACLS guideline recommends 20 to 25 mg

Continuous infusion (infusions >24 hours or infusion rates >15 mg/hour are not recommended): Initial infusion rate of 10 mg/hour; rate may be increased in 5 mg/hour increments up to 15 mg/hour as needed; some patients may respond to an initial rate of 5 mg/hour.

If diltiazem injection is administered by continuous infusion for >24 hours, the possibility of decreased diltiazem clearance, prolonged elimination half-life, and increased diltiazem and/or diltiazem metabolite plasma concentrations should be considered.

Atrial fibrillation (rate control) (off-label use): Oral: Extended release (capsule or tablet): Usual maintenance dose: 120 to 360 mg once daily (AHA/ACC/HRS [January 2014]).

Supraventricular tachycardia (ongoing management) (off-label use): Oral:

Extended release (capsule or tablet): Initial: 120 mg daily in divided doses or once daily; usual maintenance dose: 360 mg daily in divided doses or once daily (ACC/AHA/HRS [Page 2015]).

Immediate release: Initial: 120 mg daily in divided doses; usual maintenance dose: 360 mg daily in divided doses (ACC/AHA/HRS [Page 2015]).

Conversion from IV diltiazem to oral diltiazem:

Oral dose (mg daily) is approximately equal to [rate (mg/hour) x 3 + 3] x 10.

3 mg/hour = 120 mg daily

5 mg/hour = 180 mg daily

7 mg/hour = 240 mg daily

11 mg/hour = 360 mg daily

Dosing: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses (eg, 120 mg once daily using extended release capsule) and titrate to response (Aronow 2011).

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustment provided in the manufacturer’s labeling; use with caution; extensively metabolized by the liver; half-life is increased in patients with cirrhosis.

Dosing: Pediatric

Atrial tachyarrhythmias, rate control (bridge to therapy): Very limited data available: Infants ≥6 months, Children, and Adolescents: IV: Initial bolus: 0.25 mg/kg over 5 minutes (maximum dose: 20 mg/dose [average adult dose]) followed by a continuous IV infusion; reported rate range in one study was 0.05 to 0.15 mg/kg/hour. Note: Usual adult infusion rate for arrhythmia is 5 to 15 mg/hour. Dose should be individualized based on patient response. Dosing based on a small study of 10 patients with atrial tachycardia (age range: 6 months to 21 years; most patients were adolescents) who received an initial bolus of 0.25 mg/kg/dose followed by a continuous infusion titrated to effect, reported effective range was 0.05 to 0.15 mg/kg/hour (mean infusion rate: 0.11 mg/kg/hour). Rate control was achieved in 9 of the 10 patients within 10 minutes of dosing. One patient required an additional bolus of 0.25 mg/kg. Median ventricular rate of study group prior to initial bolus was 275 ± 50 beats per minute (BPM) (range: 185 to 500 BPM), which decreased to a median of 166 BPM prior to initiation of continuous infusion and decreased to a median of 123 BPM after 10 minutes of continuous infusion; blood pressure was not significantly affected by diltiazem; qualitative systolic function did not worsen in the seven patients studied (Pass 2000). Note: In adult patients, infusions >24 hours are not recommended; with administration of diltiazem infusion >24 hours, the possibility of decreased diltiazem clearance, prolonged elimination half-life, and increased diltiazem and/or diltiazem metabolite plasma concentrations should be considered. In trial of 10 pediatric patients, the median duration was 45 hours (mean: 54 hours; range: 14 to 126 hours) (Pass 2000)

Hypertension: Limited data available:

Infants and Children: Oral: Immediate-release formulations: Initial: 1.5 to 2 mg/kg/day in 3 to 4 divided doses (Flynn 2000; Park 2014); increase gradually, at 1- to 2-day intervals until optimum response is obtained; usual maximum daily dose: 3.5 mg/kg/day (Park 2014); some experts recommend a higher maximum daily dose of 6 mg/kg/day up to 360 mg/day; whichever is less (Flynn 2000). Note: Once patient is established on a total daily dose, may convert to an extended release dosage form at the appropriate interval (once or twice daily) in children able to swallow capsules whole and receiving adequate mg amount (Flynn 2000).

Adolescents (Park 2014): Oral:

Immediate-release formulations: 30 to 120 mg/dose administered 3 to 4 times daily; usual daily dosage range: 180 to 360 mg/day

Extended-release formulations:

Capsule, extended release (once daily dosing; eg, Cardizem CD, Tiazac): 120 to 300 mg once daily

Capsule, extended release (twice daily dosing; eg, Cardizem SR): 120 to 300 mg/day in 2 divided doses

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustment provided in the manufacturer’s labeling; use with caution; extensively metabolized by the liver; half-life is increased in patients with cirrhosis.

Calculations
Use: Labeled Indications

Oral: Management of hypertension; management of chronic stable angina or angina from coronary artery spasm.

Guideline recommendations: Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular end points (eg, prevention of heart failure and stroke). ACE inhibitors and ARBs are also acceptable for monotherapy. Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%) (ACC/AHA [Whelton 2017]). Note: When a calcium channel blocker is selected, the dihydropyridine class (eg, amlodipine) is typically preferred, if tolerated, over the non-dihydropyridine class (eg, diltiazem or verapamil).

Injection: Control of rapid ventricular rate in patients with atrial fibrillation or atrial flutter; conversion of paroxysmal supraventricular tachycardia (PSVT)

Guideline recommendations: The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) supraventricular tachycardia (SVT) guidelines recommends IV diltiazem as a therapeutic option for the acute treatment (ie, conversion) of a variety of SVTs (AVNRT, AVRT, and focal AT) in hemodynamically stable patients. Diltiazem is not appropriate for patients with suspected systolic heart failure or pre-excitation on ECG (ACC/AHA/HRS [Page 2015]).

Use: Off-Label: Adult

  Anal fissures (topical)Level of Evidence [A, G]

Guidelines recommend topical diltiazem as first-line therapy for the treatment of anal fissures in adults, as it is associated with fewer adverse effects than topical nitroglycerin and has a better cost profile than botulinum toxin A. Access Full Off-Label Monograph

  Atrial fibrillation (rate control) (oral)Level of Evidence [G]

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines for the management of patients with atrial fibrillation, the use of nondihydropyridine calcium channel blockers, including diltiazem, for ventricular rate control in patients with paroxysmal, persistent, or permanent atrial fibrillation is effective and recommended for this condition.

  Hypertrophic cardiomyopathyLevel of Evidence [G]

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy, the use of diltiazem is an effective and recommended treatment for the management of patients with this condition who do not tolerate verapamil or when verapamil is contraindicated.

  Idiopathic ventricular tachycardiaLevel of Evidence [C, G]

Data in a small, prospective observational study showed that diltiazem can suppress ventricular tachycardia (VT) in patients with idiopathic VT. Additional data may be necessary to further define the role of diltiazem in this condition Ref.

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death, diltiazem is an effective and recommended therapy for termination and prevention of recurrence of idiopathic VT originating from the right ventricular outflow tract or related to interfascicular reentry. Note: Calcium channel blockers should not be given to patients with VT and heart failure with a reduced ejection fraction. Calcium channel blockers are not effective for all forms of VT and may be harmful. These agents should not be given to patients with VT of unknown origin.

  Non-ST-elevation acute coronary syndromeLevel of Evidence [G]

Based on the AHA/ACC guidelines for the management of non-ST-elevation ACS (NSTE-ACS), a nondihydropyridine calcium channel blocker (eg, diltiazem) is effective and recommended to treat ongoing ischemia if beta-blocker therapy is ineffective or contraindicated and in the absence of left ventricular dysfunction, increased risk for cardiogenic shock, PR interval >0.24 seconds, or second- or third-degree AV block (without a pacemaker).

  Raynaud phenomenonLevel of Evidence [C, G]

Diltiazem for the treatment of Raynaud phenomenon has been evaluated in a limited number of controlled trials and has demonstrated beneficial effects in reducing the frequency and severity of ischemic attacks. According to evidence-based international consensus-derived recommendations for systemic sclerosis, dihydropyridine-type calcium channel blockers (specifically oral nifedipine) are considered first-line therapy in systemic sclerosis-related Raynaud phenomenon. Access Full Off-Label Monograph

  Stable narrow-complex tachycardia uncontrolled or unconverted by adenosine or vagal maneuvers or if SVT is recurrent (injection)Level of Evidence [G]

Based on the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, the use of diltiazem is effective and recommended for the management of patients with stable narrow-complex tachycardia that is recurrent or not controlled or converted by adenosine or vagal maneuvers.

  Supraventricular tachycardia (AV nodal reentrant tachycardia [AVNRT], AV reentrant tachycardia [AVRT], focal atrial tachycardia [AT], multifocal atrial tachycardia [MAT]) (ongoing management) (oral)Level of Evidence [G]

Based on the American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for the management of patients with supraventricular arrhythmias, oral diltiazem is effective and recommended for the ongoing management of hemodynamically stable patients with symptomatic supraventricular tachycardia (AVNRT, AVRT, focal AT, MAT) without pre-excitation in patients who are not candidates for, or prefer not to undergo catheter ablation. Diltiazem is not appropriate for patients with suspected systolic heart failure.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Advanced Cardiac Life Support (ACLS)/Emergency Cardiovascular Care (ECC):

AHA, “2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” October 2015.

AHA, “2010 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” November 2010.

Arrhythmias:

AHA/ACC/HRS, “2017 AHA/ACC/HRS Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death,” October 2017

AATS, “2014 AATS Guidelines for the Prevention and Management of Perioperative Atrial Fibrillation and Flutter for Thoracic Surgical Procedures,” June 2014

ACC/AHA/HRS, “Guideline for the Management of Adult Patients with Supraventricular Tachycardia” 2015

AHA/ACC/HRS, “2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation,” March 2014

Canadian Cardiovascular Society, “2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation,” 2016

Diabetes Mellitus:

American Diabetes Association, “Standards of Medical Care in Diabetes – 2018,” January 2018

Hypertension:

“2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults,” November 2017.

AHA/ACC/ASH, “Treatment of Hypertension in Patients with Coronary Artery Disease: A Scientific Statement by the American Heart Association, American College of Cardiology and American Society of Hypertension,” May 2015

“ACCF/AHA Expert Consensus Document on Hypertension in the Elderly,” 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), “2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults,” December 2013

“Medical Therapy for Pulmonary Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines,” June 2007

Hypertrophic Cardiomyopathy:

“2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy,” November 2011

“ACC/ESC Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy,” November 2003

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction,” December 2012

Pulmonary Arterial Hypertension:

CHEST Guideline and Expert Panel Report, “Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults,” August 2014

Usual Infusion Concentrations: Adult

IV infusion: 125 mg in 125 mL (total volume) (concentration: 1 mg/mL) of D5W or NS

Administration: IV

Bolus doses given over 2 minutes with continuous ECG and blood pressure monitoring. Continuous infusion should be via infusion pump. May increase infusion rate in 5 mg/hour increments as needed (maximum: 15 mg/hour). Response to bolus may require several minutes to reach maximum. Response may persist for several hours after infusion is discontinued.

Administration: Injectable Detail

pH: 3.7-4.1

Administration: Oral

Immediate release tablet (eg, Cardizem): Administer before meals and at bedtime. The manufacturers of the film-coated tablets recommend to swallow the tablet whole; do not split, crush, or chew. According to these manufacturers, crushing immediate release tablets may alter pharmacokinetics. However, crushing tablets that are prepared using a direct compression technique is acceptable. An oral suspension has been made using the immediate release tablets manufactured using a direct compression technique (Allen 1996). Brand name Cardizem tablets are prepared using a direct compression technique and may be crushed.

Long acting dosage forms: Do not open, chew, or crush; swallow whole. Administer at same time of day either morning or evening.

Cardizem CD, Cardizem LA, Cartia XT, Matzim LA: Administer without regard to meals.

Dilt XR: Administer on an empty stomach in the morning.

Taztia XT, Tiazac: Capsules may be opened and sprinkled on a spoonful of applesauce. Applesauce should not be hot and should be swallowed without chewing, followed by drinking a glass of water.

Tiazac XC [Canadian product]: Administer at bedtime

Administration: Pediatric

Oral:

Tablet, immediate release (eg, Cardizem): Administer before meals and at bedtime. The manufacturers of the film-coated tablets recommend to swallow the tablet whole; do not split, crush, or chew. According to these manufacturers, crushing immediate release tablets may alter pharmacokinetics; film coating is designed to slowly release diltiazem. However, crushing tablets that are prepared using a direct compression technique is acceptable. An oral suspension has been made using the immediate release tablets manufactured using a direct compression technique (Allen 1996). Brand name Cardizem tablets are prepared using a direct compression technique and may be crushed.

Extended-release preparations: Swallow whole; do not chew, break, or crush. Administer at the same time of day, either morning or evening.

Cardizem CD, Cardizem LA, Cartia XT, Matzim LA: May be administered with or without food, but should be administered consistently with relation to meals; administer with a full glass of water

Taztia XT and Tiazac: Capsules may be opened and sprinkled on applesauce; swallow applesauce immediately, do not chew; follow with some cool water (adults: 1 glass) to ensure complete swallowing; do not use hot applesauce; do not divide capsule contents (ie, do not administer partial doses); do not store mixture of applesauce and capsule contents, use immediately

Parenteral:

IV bolus: Pediatric patients ≥6 months of age: Administration over 5 minutes at a concentration ≤5 mg/mL with continuous ECG monitoring has been used (Pass 2000)

Continuous IV infusion: Administer as a continuous IV infusion with the use of an infusion pump with continuous ECG monitoring. Response may persist for several hours after infusion is discontinued.

Storage/Stability

Capsule, tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Avoid excessive heat (>30°C) and humidity.

Solution for injection: Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. May be stored at room temperature for up to 1 month. Following dilution to ≤1 mg/mL with D51/2NS, D5W, or NS, solution is stable for 24 hours at room temperature (15°C to 30°C (59°F to 86°F) or under refrigeration).

Solution reconstituted, intravenous (ADD-Vantage): Store at 20°C to 25°C (68°F to 77°F); do not freeze. Following reconstitution, solution is stable for 24 hours at room temperature or under refrigeration (2°C to 8°C [36°F to 46°F]).

Preparation for Administration: Adult

Solution for injection: Continuous IV infusion: Further dilute with NS, D5W, or D51/2NS to a maximum final concentration of 1 mg/mL.

Solution reconstituted, IV (ADD-Vantage): Refer to manufacturer’s labeling.

Preparation for Administration: Pediatric

Parenteral: Continuous IV infusion: Further dilute with NS, D5W, or D51/2NS to a maximum final concentration of 1 mg/mL

Compatibility

See Trissel’s IV Compatibility Database

Extemporaneously Prepared

A 12 mg/mL oral suspension may be made from tablets (regular, not extended release) and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush sixteen 90 mg tablets in a mortar and reduce to a fine powder. Add 10 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “protect from light”. Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated. Note: The tablets used within the supportive study were tablets manufactured using a direct compression technique and were not film-coated. Use of film-coated tablets to prepare an oral suspension has not been formally evaluated and may result in an unsuitable suspension. The manufacturers of the film-coated tablets do not recommend crushing. Brand name Cardizem tablets are prepared using a direct compression technique and may be crushed.

Allen LV and Erickson MA, “Stability of Baclofen, Captopril, Diltiazem Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids,” Am J Health Syst Pharm, 1996, 53(18):2179-84.[PubMed 8879325]

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, loss of strength and energy, or injection site irritation. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe dizziness, passing out, bradycardia, abnormal heartbeat, signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  High alert medication:
  Administration issues:
  International issues:
Contraindications

Oral: Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); hypotension (systolic <90 mm Hg); acute MI and pulmonary congestion

Intravenous (IV): Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); severe hypotension; cardiogenic shock; administration concomitantly or within a few hours of the administration of IV beta-blockers; atrial fibrillation or flutter associated with accessory bypass tract (eg, Wolff-Parkinson-White syndrome, short PR syndrome); ventricular tachycardia (with wide-complex tachycardia [QRS ≥0.12 seconds], must determine whether origin is supraventricular or ventricular)

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; use in women of childbearing potential; concurrent use with intravenous dantrolene; concurrent use with ivabradine.

Warnings/Precautions

Concerns related to adverse effects:

• Conduction abnormalities: May cause first-, second-, and third-degree AV block or sinus bradycardia; risk increases with agents known to slow cardiac conduction.

• Dermatologic reactions: Transient dermatologic reactions have been observed with use; if reaction persists, discontinue. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and/or exfoliative dermatitis have been reported.

• Hepatic effects: Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed and frequently resolve spontaneously. Significant elevations in hepatic transaminases (eg, alkaline phosphatase, LDH, AST, ALT) and signs of acute hepatic injury have also been observed 1 to 8 weeks after therapy initiation and have been reversible upon discontinuation.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient’s clinical condition.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Hypertrophic obstructive cardiomyopathy (HOCM): Use with caution in patients with HOCM; routine use is currently not recommended due to insufficient evidence (Maron 2003).

• Left ventricular dysfunction: Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition. The ACCF/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACCF/AHA [Yancy 2013]).

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: IV: Unless otherwise contraindicated, appropriate vagal maneuvers should be attempted prior to administration of IV diltiazem. Use with caution in patients hemodynamically compromised; continuously monitor ECG and blood pressure during administration (especially during continuous IV infusion). Initial use should be, if possible, in a setting where monitoring and resuscitation equipment, including DC cardioversion/defibrillation, are present.

Geriatric Considerations

Elderly may experience a greater hypotensive response; constipation may be encountered more often in elderly. Calcium channel blockers are no more effective in elderly than other therapies; however, they do not cause significant CNS effects which is an advantage over other antihypertensive agents (eg, beta-blockers, clonidine).

The AHA/ACC/ASH 2015 scientific statement on the treatment of hypertension in patients with CAD warns to use caution to avoid decreases in DBP <60 mm Hg especially in patients >60 years of age since reduced coronary perfusion may occur. When lowering SBP in older hypertensive patients with wide pulse pressures, very low DBP values (<60 mm Hg) may result. In patients with obstructive CAD, clinicians should lower blood pressure slowly and carefully monitor for any untoward signs or symptoms, especially those resulting from myocardial ischemia and worsening heart failure (AHA/ACC/ASH [Rosendorff 2015]).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG 2013). Women with hypertrophic cardiomyopathy who are controlled with diltiazem prior to pregnancy may continue therapy, but increased fetal monitoring is recommended (Gersh 2011).

Breast-Feeding Considerations

Diltiazem is present in breast milk in concentrations similar to those in the maternal plasma (Okada 1985). Breastfeeding is not recommended by the manufacturer.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Note: Frequencies represent ranges for various dosage forms. Patients with impaired ventricular function and/or conduction abnormalities may have higher incidence of adverse reactions.

>10%:

Cardiovascular: Edema (2% to 15%)

Central nervous system: Headache (5% to 12%)

2% to 10%:

Cardiovascular: Atrioventricular block (2% to 8%; first degree), edema (2% to 8%; lower limb), bradycardia (2% to 6%), hypotension (<2% to 4%), vasodilatation (2% to 3%), extrasystoles (2%), flushing (1% to 2%), palpitations (1% to 2%)

Central nervous system: Dizziness (3% to 10%), pain (6%), nervousness (2%)

Dermatologic: Skin rash (1% to 4%)

Endocrine & metabolic: Gout (1% to 2%)

Gastrointestinal: Dyspepsia (1% to 6%), constipation (<2% to 4%), vomiting (2%), diarrhea (1% to 2%)

Local: Injection site reaction (4%; itching, burning)

Neuromuscular & skeletal: Weakness (1% to 4%), myalgia (2%)

Respiratory: Rhinitis (<2% to 10%), pharyngitis (2% to 6%), dyspnea (1% to 6%), bronchitis (1% to 4%), cough (≤3), sinus congestion (1% to 2%)

<2%, postmarketing, and/or case reports: Abnormal dreams, abnormal gait, albuminuria, alopecia, amblyopia, amnesia, angina pectoris, angioedema, anorexia, asystole, atrioventricular block (second or third degree), bruise, bundle branch block, cardiac arrhythmia, cardiac failure, crystalluria, depression, drowsiness, dysgeusia, ECG abnormality, epistaxis, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, gingival hyperplasia, gynecomastia, hallucination, hemolytic anemia, hyperglycemia, hypersensitivity angiitis, hypersensitivity reaction, hyperuricemia, impotence, increased creatine phosphokinase, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, increased thirst, insomnia, leukopenia, muscle cramps, myopathy, nausea, neck stiffness, nocturia, pain, paresthesia, personality changes, petechia, polyuria, prolonged bleeding time, pruritus, purpura, retinopathy, skin photosensitivity, Stevens-Johnson syndrome, syncope, tachycardia, thrombocytopenia, tinnitus, toxic epidermal necrolysis, tremor, urticaria, ventricular premature contractions, weight gain, xerostomia

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak), CYP3A4 (moderate)

Drug Interactions 

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Risk C: Monitor therapy

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification

Alfentanil: DilTIAZem may increase the serum concentration of Alfentanil. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk C: Monitor therapy

AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).Risk C: Monitor therapy

Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Risk C: Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Risk X: Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

Aspirin: Calcium Channel Blockers (Nondihydropyridine) may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

AtorvaSTATin: May increase the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Risk D: Consider therapy modification

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy

Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Risk D: Consider therapy modification

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy

Beta-Blockers: Calcium Channel Blockers (Nondihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin. Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details.Risk C: Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Risk X: Avoid combination

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Risk C: Monitor therapy

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Risk X: Avoid combination

Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased.Risk D: Consider therapy modification

BusPIRone: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of BusPIRone. Risk C: Monitor therapy

Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy

Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy

Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

CarBAMazepine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider empiric reductions in carbamazepine dose with initiation of nondihydropyridine calcium channel blockers. Monitor for increased toxic effects of carbamazepine and reduced therapeutic effects of the calcium channel blocker. Risk D: Consider therapy modification

Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Risk D: Consider therapy modification

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4. Risk D: Consider therapy modification

Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloNIDine: May enhance the AV-blocking effect of Calcium Channel Blockers (Nondihydropyridine). Sinus node dysfunction may also be enhanced. Risk C: Monitor therapy

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Risk X: Avoid combination

Codeine: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification

Colestipol: May decrease the absorption of DilTIAZem. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Copanlisib: DilTIAZem may increase the serum concentration of Copanlisib. Risk C: Monitor therapy

Corticosteroids (Systemic): DilTIAZem may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

CycloSPORINE (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Exceptions: Alitretinoin (Systemic); Praziquantel; Trabectedin; Vinorelbine. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers (Nondihydropyridine). Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers (Nondihydropyridine). Management: This interaction has only been described with intravenous dantrolene administration. Risk X: Avoid combination

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk X: Avoid combination

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy

Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Use lower starting doses of the nondihydropyridine calcium channel blockers (i.e., verapamil, diltiazem), and only consider increasing calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Efavirenz: May decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided. Risk D: Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Risk D: Consider therapy modification

Encorafenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and moderate CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose to one-half of the encorafenib dose used prior to initiation of the CYP3A4 inhibitor. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Risk D: Consider therapy modification

Esmolol: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Esmolol. Management: Administration of IV verapamil or diltiazem together with esmolol is contraindicated if one agent is given while the effects of the other are still present. Canadian esmolol labeling specifies that use within 24 hours is contraindicated. Risk D: Consider therapy modification

Estrogen Derivatives: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for most indications. See full monograph or prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Risk D: Consider therapy modification

Fingolimod: DilTIAZem may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Risk X: Avoid combination

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy

Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase the serum concentration of DilTIAZem. Risk C: Monitor therapy

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. Risk D: Consider therapy modification

Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of ECGs, should be used if halofantrine is combined with moderate CYP3A4 inhibitors. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions.Risk D: Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Risk C: Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Risk X: Avoid combination

Ivabradine: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Ivabradine. Ivabradine may enhance the QTc-prolonging effect of Calcium Channel Blockers (Nondihydropyridine). Specifically, the QTc prolonging effects of bepridil may be enhanced. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ivabradine. Specifically, verapamil or diltiazem may increase serum ivabradine concentrations. Risk X: Avoid combination

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lithium: Calcium Channel Blockers (Nondihydropyridine) may enhance the neurotoxic effect of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Risk X: Avoid combination

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Lovastatin: May increase the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of Lovastatin. Management: Initiate lovastatin at a maximum adult dose of 10 mg/day, and do not exceed 20 mg/day, in patients receiving diltiazem. Monitor closely for signs of HMG-CoA reductase inhibitor toxicity (e.g., myositis, rhabdomyolysis).Risk D: Consider therapy modification

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products. Risk D: Consider therapy modification

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Risk D: Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Manidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Midostaurin: DilTIAZem may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and diltiazem if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Risk X: Avoid combination

Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Risk X: Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily. Risk D: Consider therapy modification

Opioids (Anilidopiperidine): May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Opioids (Anilidopiperidine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy

OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Risk D: Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If used, monitor for CCB toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Saquinavir, tipranavir, and darunavir/cobicistat use with bepridil is contraindicated. Risk D: Consider therapy modification

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

QuiNIDine: DilTIAZem may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy

Ranolazine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ranolazine. Management: Limit ranolazine dose to a maximum of 500 mg twice daily when used with diltiazem or verapamil. Risk D: Consider therapy modification

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Risk D: Consider therapy modification

Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Risk C: Monitor therapy

Regorafenib: May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of DilTIAZem. Risk X: Avoid combination

Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification

Rupatadine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine. Risk C: Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Ruxolitinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib. Risk C: Monitor therapy

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin. Risk C: Monitor therapy

Sildenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy

Silodosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Risk X: Avoid combination

Simvastatin: May increase the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg/day and diltiazem 240 mg/day; avoid Simcor (simvastatin/niacin) because fixed simvastatin doses exceed the maximum. Risk D: Consider therapy modification

Sirolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Systemic). Risk C: Monitor therapy

Tacrolimus (Topical): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tezacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor (100 mg/150 mg) should be given in the morning, every other day. Ivacaftor (150 mg) alone should be given in the morning, every other day on alternate days from tezacaftor/ivacaftor. Risk D: Consider therapy modification

Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor. See labeling or full interaction monograph for specific recommendations. Use of Samsca with moderate CYP3A4 ihibitors should generally be avoided. Risk D: Consider therapy modification

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Risk C: Monitor therapy

Udenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil. Risk C: Monitor therapy

Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Risk X: Avoid combination

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Risk D: Consider therapy modification

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy

Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Risk D: Consider therapy modification

Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Food Interactions

Grapefruit juice may increase the serum concentration of diltiazem. Management: Monitor response to diltiazem with concurrent use.

Monitoring Parameters

Liver function tests, kidney function, blood pressure, ECG, heart rate; consult individual institutional policies and procedures. Ventricular rate control in patients with atrial fibrillation or flutter: Patients who respond, usually have at least a 20% decrease in ventricular response rate or a rate <100 beats/minute.

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2018):

Patients ≥18 to ≤65 years: Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Patients ≥18 to ≤65 years and at high risk of cardiovascular disease: Goal of therapy is SBP <130 mm Hg and DBP <80 mm Hg (if can be achieved without undue treatment burden).

Patients ≥65 years (healthy or complex/intermediate health): Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Patients ≥65 years (very complex/poor health): Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

Advanced Practitioners Physical Assessment/Monitoring

Obtain liver function tests and kidney function tests. Assess blood pressure, heart rate, and ECG. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. IV requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Assess therapeutic effectiveness according to use (hypertension, angina, atrial fib/flutter, or PSVT).

Nursing Physical Assessment/Monitoring

Check ordered labs and report any abnormalities. Monitor blood pressure, heart rate and ECG as ordered. IV requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Monitor therapeutic effectiveness according to use (hypertension, angina, atrial fib/flutter, or PSVT).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 12 Hour, Oral, as hydrochloride:

Generic: 60 mg, 90 mg, 120 mg

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Cardizem CD: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg [contains brilliant blue fcf (fd&c blue #1)]

Cartia XT: 120 mg, 180 mg, 240 mg

Cartia XT: 300 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40, fd&c red #40 aluminum lake, fd&c yellow #10 (quinoline yellow), fd&c yellow #10 aluminum lake]

Dilt-XR: 120 mg, 180 mg, 240 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow)]

dilTIAZem CD: 120 mg [DSC]

dilTIAZem CD: 180 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

dilTIAZem CD: 240 mg [DSC] [contains fd&c yellow #10 (quinoline yellow)]

Taztia XT: 120 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]

Taztia XT: 180 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 (quinoline yellow), fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]

Taztia XT: 240 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]

Taztia XT: 300 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 (sunset yellow)]

Taztia XT: 360 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake]

Tiazac: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

Generic: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Solution, Intravenous, as hydrochloride:

Generic: 25 mg/5 mL (5 mL); 50 mg/10 mL (10 mL); 125 mg/25 mL (25 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Generic: 50 mg/10 mL (10 mL [DSC]); 125 mg/25 mL (25 mL [DSC])

Solution Reconstituted, Intravenous, as hydrochloride:

Generic: 100 mg (1 ea)

Tablet, Oral, as hydrochloride:

Cardizem: 30 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]

Cardizem: 60 mg [scored; contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, methylparaben]

Cardizem: 120 mg [scored; contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake, methylparaben]

Generic: 30 mg, 60 mg, 90 mg, 120 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Cardizem LA: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Matzim LA: 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Generic: 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 12 Hour, Oral, as hydrochloride:

Generic: 60 mg [DSC], 90 mg [DSC], 120 mg [DSC], 60 mg/12 hr [DSC], 120 mg/12 hr [DSC]

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Cardizem CD: 120 mg, 180 mg, 240 mg, 300 mg

Tiazac: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg [contains BRILLIANT BLUE FCF (FD&C BLUE #1), FD&C RED #40]

Generic: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg

Solution, Intravenous:

Generic: 5 mg/mL (5ml, 10ml)

Tablet, Oral, as hydrochloride:

Generic: 30 mg, 60 mg

Tablet Extended Release 24 Hour, Oral:

Tiazac XC: 120 mg, 360 mg, 180 mg/24 hr, 240 mg/24 hr, 300 mg/24 hr

Anatomic Therapeutic Chemical (ATC) Classification
  • C08DB01
Generic Available (US)

Yes

Pricing: US

Capsule ER 24 Hour Therapy Pack (Cardizem CD Oral)

120 mg (per each): $29.85

180 mg (per each): $37.66

240 mg (per each): $51.05

300 mg (per each): $66.87

360 mg (per each): $97.57

Capsule ER 24 Hour Therapy Pack (Cartia XT Oral)

120 mg (per each): $1.20

180 mg (per each): $1.45

240 mg (per each): $2.05

300 mg (per each): $2.66

Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Beads Oral)

120 mg (per each): $0.75 – $1.04

180 mg (per each): $0.90 – $1.25

240 mg (per each): $1.28 – $1.78

300 mg (per each): $1.66 – $2.30

360 mg (per each): $1.69 – $2.59

420 mg (per each): $1.77 – $2.85

Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Coated Beads Oral)

120 mg (per each): $0.93 – $1.20

180 mg (per each): $1.12 – $1.45

240 mg (per each): $1.59 – $2.05

300 mg (per each): $2.06 – $2.66

360 mg (per each): $9.83 – $10.23

Capsule ER 24 Hour Therapy Pack (dilTIAZem HCl ER Oral)

120 mg (per each): $1.03

180 mg (per each): $1.34

240 mg (per each): $1.43

Capsule ER 24 Hour Therapy Pack (Taztia XT Oral)

120 mg (per each): $1.14

180 mg (per each): $1.38

240 mg (per each): $1.96

300 mg (per each): $2.54

360 mg (per each): $2.59

Capsule ER 24 Hour Therapy Pack (Tiazac Oral)

120 mg (per each): $2.36

180 mg (per each): $2.85

240 mg (per each): $4.05

300 mg (per each): $5.24

360 mg (per each): $5.34

420 mg (per each): $5.60

Capsule, 12-hour (dilTIAZem HCl ER Oral)

60 mg (per each): $3.17 – $3.97

90 mg (per each): $3.62 – $4.67

120 mg (per each): $4.73 – $6.52

Solution (dilTIAZem HCl Intravenous)

25 mg/5 mL (per mL): $0.51 – $0.70

50 mg/10 mL (per mL): $0.36 – $0.52

125 mg/25 mL (per mL): $0.28 – $0.55

Solution (reconstituted) (dilTIAZem HCl Intravenous)

100 mg (per each): $14.51

Tablet, 24-hour (Cardizem LA Oral)

120 mg (per each): $4.56

180 mg (per each): $4.82

240 mg (per each): $5.41

300 mg (per each): $7.03

360 mg (per each): $7.56

420 mg (per each): $8.19

Tablet, 24-hour (dilTIAZem HCl ER Coated Beads Oral)

180 mg (per each): $2.86

240 mg (per each): $3.20

300 mg (per each): $4.16

360 mg (per each): $4.48

420 mg (per each): $4.85

Tablet, 24-hour (Matzim LA Oral)

180 mg (per each): $2.98

240 mg (per each): $3.34

300 mg (per each): $4.34

360 mg (per each): $4.67

420 mg (per each): $5.06

Tablets (Cardizem Oral)

30 mg (per each): $7.68

60 mg (per each): $12.05

120 mg (per each): $22.18

Tablets (dilTIAZem HCl Oral)

30 mg (per each): $0.18 – $1.00

60 mg (per each): $0.28 – $1.57

90 mg (per each): $0.86 – $2.14

120 mg (per each): $2.88

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization; produces relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina.

Pharmacodynamics/Kinetics

Onset of action: Oral: Immediate release tablet: 30 to 60 minutes; IV: Bolus: 3 minutes

Duration: IV: Bolus: 1 to 3 hours; Continuous infusion (after discontinuation): 0.5 to 10 hours

Absorption: Immediate release tablet: ~98%; Extended release capsule: ~93% to >95%

Distribution: Vd: 3 to 13 L/kg

Protein binding: 70% to 80%

Metabolism: Hepatic (extensive first-pass effect) via CYP-450 and conjugation; forms metabolites N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-Nmonodesmethyldiltiazem, desacetyl-O-desmethyldiltiazem, and desacetyl-N, O-desmethyldiltiazem; following single IV injection, plasma concentrations of N-monodesmethyldiltiazem and desacetyldiltiazem are typically undetectable; however, these metabolites accumulate to detectable concentrations following 24-hour constant rate infusion.

Bioavailability: Oral: ~40% (undergoes extensive first-pass metabolism)

Half-life elimination: Immediate release tablet: 3 to 4.5 hours; Extended release tablet: 6 to 9 hours; Extended release capsules: 4 to 9.5 hours; IV: single dose: ~3.4 hours; continuous infusion: 4 to 5 hours

Time to peak, serum: Immediate release tablet: 2 to 4 hours; Extended release tablet: 11 to 18 hours; Extended release capsule: 10 to 14 hours

Excretion: Urine (2% to 4% as unchanged drug); feces

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Bioavailability is increased, and half-life is prolonged.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Diltiazem has been reported to cause >10% incidence of gingival hyperplasia; usually disappears with discontinuation (consultation with physician is suggested).

Effects on Bleeding

No information available to require special precautions

Index Terms

Diltiazem HCl in 0.9% NaCl; Diltiazem Hcl/D5w; Diltiazem Hydrochloride

FDA Approval Date
November 05, 1982
References

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Allen LV Jr, Erickson MA 3rd. Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and flecainide acetate in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53(18):2179-2184.[PubMed 8879325]

American College of Obstetricians and Gynecologists (ACOG), Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88.[PubMed 24150027]

American Diabetes Association (ADA). Standards of medical care in diabetes—2018. Diabetes Care. 2018;41(suppl 1):S1-S159. http://care.diabetesjournals.org/content/41/Supplement_1. Accessed June 18, 2018.

Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017.[PubMed 25260718]

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Aronow WS, Fleg JL, Pepine CJ, et al, “ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” Circulation, 2011, 123(21):2434-506.[PubMed 21518977]

Badesch DB, Abman SH, Simonneau G, et al, “Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines,” Chest, 2007, 131(6):1917-28.[PubMed 17565025]

Cardizem (diltiazem) [prescribing information]. Bridgewater, NJ: Valeant; November 2016.

Cardizem CD (diltiazem) [prescribing information]. Bridgewater, NJ: Valeant; January 2017.

Cardizem CD (diltiazem) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; April 2018.

Cardizem LA (diltiazem) [prescribing information]. Bridgewater, NJ: Valeant; November 2016.

Cartia XT (diltiazem) [prescribing information]. Parsippany, NJ: Actavis; December 2014.

Dilt-XR (diltiazem) [prescribing information]. Weston, FL: Apotex; July 2012.

Diltiazem injection [prescribing information]. Lake Forest, IL: Akorn; June 2014.

Diltiazem injection [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; November 2010.

Diltiazem injection reconstituted [prescribing information]. Lake Forest, IL: Hospira; January 2008.

Ellenbogen KA, Dias VC, and Cardello FP, “Safety and Efficacy of Intravenous Diltiazem in Atrial Fibrillation or Atrial Flutter,” Am J Cardiol, 1995, 75(1):45-9.[PubMed 7801862]

Field JM, Hazinski MF, Sayre MR, et al, “Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):640-56.[PubMed 20956217]

Fihn SD, Gardin JM, Abrams J, et al, “2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons,” Circulation, 2012, 126(25):3097-137.[PubMed 23166211]

Flynn JT and Pasko DA, “Calcium Channel Blockers: Pharmacology and Place in Therapy of Pediatric Hypertension,” Pediatr Nephrol, 2000, 15(3-4):302-16.[PubMed 11149130]

Gersh BJ, Maron BJ, Bonow RO, et al, “2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 124(24):e783-831.[PubMed 22068434]

Gibbons RJ, Abrams J, Chatterjee K, et al; American College of Cardiology; American Heart Association Task Force on practice guidelines (Committee on the Management of Patients with Chronic Stable Angina). ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 2003;41(1):159-168.[PubMed 12570960]

Gibson RS, Boden WE, Theroux P, et al, “Diltiazem and Reinfarction With Non-Q-Wave Myocardial Infarction,” N Engl J Med, 1986, 315(7):423-9.[PubMed 3526151]

Gill JS, Ward DE, Camm JA. Comparison of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia. Pacing Clin Electrophysiol. 1992;15(11 pt 2):2122-2126.[PubMed 1279611]

Go AS, Bauman M, King SM, et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention [published online November 15, 2013]. Hypertension.[PubMed 24243703]

James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.[PubMed 24352797]

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online March 28, 2014]. Circulation.[PubMed 24682347]

Karth GD, Geppert A, Neunteufl T, et al, “Amiodarone vs. Diltiazem for Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias,” Crit Care Med, 2001, 29(6):1149-53.[PubMed 11395591]

Kleinman ME, Chameides L, Schexnayder SM, et al, “Part 14: Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):876-908.[PubMed 20956230]

Maron BJ, McKenna WJ, Danielson GK, et al, “American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines,” J Am Coll Cardiol, 2003, 42(9):1687-713.[PubMed 14607462]

Matzim LA (diltiazem) [prescribing information]. Parsippany, NJ: Actavis Pharma; May 2018.

Neumar RW, Otto CW, Link MS, et al, “Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):729-67.

Okada M, Inoue H, Nakamura Y, et al, “Excretion of Diltiazem in Human Milk,” N Engl J Med, 1985, 312(15):992-3.[PubMed 3974691]

Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016;67(13):e27-e115.[PubMed 26409259]

Pass RH, Liberman L, Al-Fayaddh M, et al, “Continuous Intravenous Diltiazem Infusion for Short-Term Ventricular Rate Control in Children,” Am J Cardiol, 2000, 86(5):559-62, A9.[PubMed 11009280]

Phillips BG, Gandhi AJ, Sanoski CA, et al, “Comparison of Intravenous Diltiazem and Verapamil for the Acute Treatment of Atrial Fibrillation and Atrial Flutter,” Pharmacotherapy, 1997, 17(6):1238-45.[PubMed 9399606]

Roberts SA, Diaz C, Nolan PE, et al, “Effectiveness and Costs of Digoxin Treatment for Atrial Fibrillation and Flutter,” Am J Cardiol, 1993, 72(7):567-73.[PubMed 8362772]

Rosendorff C, Lackland DT, Allison M, et al; American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: A scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Soc Hypertens. 2015;9(6):453-498.[PubMed 25840695]10.1016/j.jash.2015.03.002

Skanes AC, Healey JS, Cairns JA, et al, “Focused 2012 Update of the Canadian Cardiovascular Society Atrial Fibrillation Guidelines: Recommendations for Stroke Prevention and Rate/Rhythm Control,” Can J Cardiol, 2012, 28(2):125-36.[PubMed 22433576]

Steele RM, Schuna AA, and Schreiber RT, “Calcium Antagonist-Induced Gingival Hyperplasia,” Ann Intern Med, 1994, 120(8):663-4.[PubMed 8135450]

Taztia XT (diltiazem) [prescribing information]. Parsippany, NJ: Watson Pharma; September 2011.

“The Effect of Diltiazem on Mortality and Reinfarction After Myocardial Infarction. The Multicenter Diltiazem Postinfarction Trial Research Group,” N Engl J Med, 1988, 319(7):385-92.[PubMed 2899840]

Tiazac (diltiazem) [prescribing information]. Bridgewater, NJ: Valeant; November 2016.

Tiazac (diltiazem) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; March 2017.

Tiazac XC (diltiazem) [product monograph]. Laval, Quebec, Canada: Valeant Canada; March 2017.

Wann SL, Curtis AB, January CT, et al, “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 123 (1):104-23.[PubMed 21173346]

Weber MA, Schiffrin EL, White WB, et al, Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14-26.[PubMed 24341872]

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online ahead of print on November 13, 2017.]. Hypertension. 2017. doi: 10.1161/HYP.0000000000000065.[PubMed 29133356]

White WB, Lacourciere Y, Gana T, et al, “Effects of Graded-Release Diltiazem Versus Ramipril, Dosed at Bedtime, on Early Morning Blood Pressure, Heart Rate, and the Rate-Pressure Product,” Am Heart J, 2004, 148(4):628-34.[PubMed 15459593]

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327.[PubMed 23741058]

Brand Names: International

Acalix (AR, PY, VE); Adizem (IE, LU, SY); Adizem XL (LB, TR); Adizem-CD (IL); Adizem-XL (IE); Aldizem (HR, SI); Altiazem (BG, HK, IT, LV); Altiazem Retard (IT); Altiazem RR (EE, RU); Andico (LK); Angiodrox (ES); Angiotrofen (CR, DO, GT, HN, NI, PA, SV); Angiotrofin (MX); Angiotrofin Retard (MX); Angiozem (PH); Angitect (EG); Angizem (IT, LK); Apo-diltiazem CD (NZ); Balcor (BR); Beatizem (SG); Bi-Tildiem (FR); Blocalcin (HU, SK); Calcicard (GB); Calnurs (JP); Cardiazem (KR); Cardil (AE, BD, BG, BH, DK, IS, LT, MY, QA, RU); Cardil Retard (GR); Cardium (SG); Cardizem (AU, BD, BR, DK, FI, NO, NZ, SE); Cardizem CD (AU, BR, NZ); Cardizem Retard (DK, FI, SE, TW); Cardizem SR (BD, BR); Cardizem Unotard (TW); Cordila SR (ID); Cordizem (MY); Corzem (JO); Dasav (MX); Dazil (AE, BH, CY, IQ, IR, JO, KW, LY, MT, OM, SA, SY, YE); Deltazen (FR); Denazox (MT); Diacor LP (FR); Diacordin (SK); Diladel (IT); Dilatam (ZA); Dilatam 120 SR (IL); Dilatam 240 CD (IL); Dilatame (AT); Dilbres (ID); Dilcardia (BF, BJ, CI, ET, GB, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TH, TN, TZ, UG, ZA, ZM, ZW); Dilconton XL-120 (LK); Dilcor (DK); Dilem SR (TH); Dilfar (PT); Dilrene (CZ, FR, HU); Dilta-Hexal (LU); Diltahexal (DE, LU); Diltam (IE); Diltan (BB, BM, BS, BZ, GY, HU, JM, SR, TT); Diltan SR (AE, BH, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Diltelan (KR, TW); Diltelan Depot (IE); Dilteran SR (KR); Diltiazem-B (HU); Diltiazem-Ethypharm (LU); Diltiazem-Xl (LU); Diltiazyn (CO); Diltime (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Dilzanton (DE); Dilzem (AE, AT, AU, BH, CH, CY, CZ, DE, EG, FI, HR, HU, IE, IN, IQ, IR, JO, KW, LK, LY, NZ, OM, PK, PL, QA, RO, SA, SY, TH, YE); Dilzem LA (NZ); Dilzem Retard (AE, AT, BH, CY, CZ, DE, IQ, IR, JO, KW, LB, LV, LY, OM, QA, SA, SY, YE); Dilzem RR (CH); Dilzem SR (CY, GB, NZ, VN); Dilzene (IT); Dilzereal 90 Retard (DE); Dilzicardin (DE); Dinisor Retard (ES); DTM (IN); Entrydil (IE); Ergolan (CN); Gadoserin (JP); Hagen (TW); Hart (PY); Helsibon (JP); Herben (KR); Herbesser (JP, MY, TH, TW, VN); Herbesser 180 SR (HK); Herbesser 60 (MY, TH); Herbesser 90 SR (HK, MY, SG, TH); Herbesser R100 (HK, JP); Herbesser R200 (HK, JP); Herbessor (SG); Herbessor 30 (MY); Heresser 90SR (LK); Hesor (TW); Incoril (EC); Iski (IN); Kaizem CD (IN); Lytelsen (JP); Masdil (ES); Metazem (IE); Mono-Tildiem (LU); Mono-Tildiem SR (SG); Monotildiem (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Myonil (DK); Myonil Retard (DK); Neocard (BD); Pazeadin (JP); Progor (TH, TW); Riazem (QA); Surazem (LU); Telzim (EG); Tiadil (PT); Tilazem (AR, CL, CO, MX, PE, UY, ZA); Tilazem 90 (ZA); Tildiem (BE, BH, CH, CL, FR, GB, GR, IE, IT, JO, KW, LU, MY, NL, QA, SA, VN); Tildiem CR (NL); Tildiem LA (GB); Tildiem Retard (GR); Tizem (BD); Vasocardol CD (AU); Zaldem (LB); Zandil (PH); Zemtrial (PH); Ziruvate (JP)

Diltiazem (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dil TYE a zem)

Brand Names: US

Cardizem; Cardizem CD; Cardizem LA; Cartia XT; Dilt-XR; dilTIAZem CD [DSC]; Matzim LA; Taztia XT; Tiazac

Brand Names: Canada

ACT Diltiazem CD; ACT Diltiazem T; Apo-Diltiaz; Apo-Diltiaz CD; Apo-Diltiaz SR; Apo-Diltiaz TZ; Cardizem CD; Diltiazem Hydrochloride Injection; Diltiazem TZ; Diltiazem-CD; PMS-Diltiazem CD; Sandoz-Diltiazem CD; Sandoz-Diltiazem T; Teva-Diltiazem; Teva-Diltiazem CD; Teva-Diltiazem HCL ER Capsules; Tiazac; Tiazac XC

What is this drug used for?
  • It is used to treat high blood pressure.
  • It is used to treat a type of long-term chest pain (stable angina) in some people.
  • It is used to treat certain types of abnormal heartbeats.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to diltiazem or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have certain types of abnormal heartbeats. There are many types of abnormal heartbeats with which this drug must not be used. Ask your doctor or pharmacist if you are not sure.
  • If you have low blood pressure.
  • If you have had a recent heart attack.
  • If you are taking ivabradine.
  • If you are taking rifampin.
  • If you are breast-feeding or plan to breast-feed.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • You may need to have an ECG checked before starting this drug and while taking it. Talk with your doctor.
  • If you are taking this drug and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Long-acting capsules (24 hour):
  • You may need to avoid drinking alcohol with some products. Talk with your doctor or pharmacist to see if you need to avoid drinking alcohol with this drug.
  • All other products:
  • Talk with your doctor before you drink alcohol.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Very bad dizziness or passing out.
  • Slow heartbeat.
  • A new or worse heartbeat that does not feel normal.
  • Heart failure has gotten worse in some people taking this drug. If you have heart failure, talk with your doctor. Call your doctor right away if you have shortness of breath, a big weight gain, or swelling in the arms or legs.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All oral products:
  • Headache.
  • Dizziness.
  • Feeling tired or weak.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • To gain the most benefit, do not miss doses.
  • Swallow whole. Do not chew, break, or crush.
  • Take this drug at the same time of day.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Long-acting capsules (24 hour):
  • Some drugs may need to be taken with food or on an empty stomach. For some drugs it does not matter. Check with your pharmacist about how to take this drug.
  • Some products may be opened and sprinkled on a spoonful of applesauce. Some products must be swallowed whole. Check with your pharmacist to see if you can open this product.
  • All other oral products:
  • Take with or without food.
  • Injection:
  • It is given as a shot into a vein.
  • It is given as an infusion into a vein over a period of time.
What do I do if I miss a dose?
  • All oral products:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Injection:
  • Call your doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Diltiazem (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dil TYE a zem)

Brand Names: US

Cardizem; Cardizem CD; Cardizem LA; Cartia XT; Dilt-XR; dilTIAZem CD [DSC]; Matzim LA; Taztia XT; Tiazac

Brand Names: Canada

ACT Diltiazem CD; ACT Diltiazem T; Apo-Diltiaz; Apo-Diltiaz CD; Apo-Diltiaz SR; Apo-Diltiaz TZ; Cardizem CD; Diltiazem Hydrochloride Injection; Diltiazem TZ; Diltiazem-CD; PMS-Diltiazem CD; Sandoz-Diltiazem CD; Sandoz-Diltiazem T; Teva-Diltiazem; Teva-Diltiazem CD; Teva-Diltiazem HCL ER Capsules; Tiazac; Tiazac XC

What is this drug used for?
  • It is used to treat high blood pressure.
  • It is used to treat a type of long-term chest pain (stable angina) in some people.
  • It is used to treat certain types of abnormal heartbeats.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has certain types of abnormal heartbeats. There are many types of abnormal heartbeats with which this drug must not be used. Ask the doctor or pharmacist if you are not sure.
  • If your child has low blood pressure.
  • If your child has had a recent heart attack.
  • If your child is taking ivabradine.
  • If your child is taking rifampin.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs.
  • Have your child’s blood pressure and heart rate checked often. Talk with your child’s doctor.
  • Your child may need to have an ECG checked while taking this drug. Talk with the doctor.
  • If your child is taking this drug and has high blood pressure, talk with the doctor before giving OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • If your child drinks grapefruit juice or eats grapefruit often, talk with your child’s doctor.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Very bad dizziness or passing out.
  • Slow heartbeat.
  • A new or worse heartbeat that does not feel normal.
  • Heart failure has gotten worse in some people taking this drug. If your child has heart failure, talk with your child’s doctor. Call your child’s doctor right away if your child has shortness of breath, a big weight gain, or swelling in the arms or legs.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All oral products:
  • Headache.
  • Dizziness.
  • Feeling tired or weak.
  • Injection:
  • Irritation where the shot is given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • To gain the most benefit, do not miss giving your child doses.
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Give this drug at the same time of day.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Long-acting capsules (24 hour):
  • Some drugs may need to be given with food or on an empty stomach. For some drugs, it does not matter. Check with your pharmacist about how to give this drug to your child.
  • Some products may be opened and sprinkled on a spoonful of applesauce. Some products must be swallowed whole. Check with your pharmacist to see if you can open this product.
  • All other oral products:
  • Give this drug with or without food.
  • Injection:
  • It is given as a shot into a vein.
  • It is given as an infusion into a vein over a period of time.
What do I do if my child misses a dose?
  • All oral products:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.