Mirtazapine (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressant drugs:
Pronunciation

(mir TAZ a peen)

Brand Names: US

Remeron; Remeron SolTab

Brand Names: Canada

APO-Mirtazapine; Auro-Mirtazapine; Auro-Mirtazapine OD; DOM-Mirtazapine; JAMP-Mirtazapine; MYLAN-Mirtazapine; PMS-Mirtazapine; PRO-Mirtazapine; Remeron; Remeron RD; RIVA-Mirtazapine; SANDOZ Mirtazapine; TEVA-Mirtazapine; TEVA-Mirtazapine OD

Pharmacologic Category

Antidepressant, Alpha-2 Antagonist

Dosing: Adult

Headache, chronic tension-type, prophylaxis (alternative agent) (off-label use): Oral: Initial: 15 mg once daily at bedtime; may increase after 1 week to 30 mg/day based on response and tolerability (Bendtsen 2004)

Major depressive disorder (unipolar): Oral: Initial: 15 mg once daily at bedtime; increase dose in 15 mg increments at intervals no less than every 1 to 2 weeks based on response and tolerability. Maximum dose: 45 mg/day (product labeling); however, doses up to 60 mg/day have been used in clinical trials (VA/DoD 2016; Watanabe 2011).

Panic disorder (alternative agent) (off-label use): Note: As monotherapy or adjunctive therapy in patients nonresponsive to SSRIs. Oral: Initial: 15 mg once daily at bedtime; may increase in increments of 15 mg at intervals of no less than 1 week based on response and tolerability, up to a usual maximum of 45 mg once daily (product labeling). Average doses in clinical trials were ~30 mg/day; doses up to 60 mg/day have been evaluated (Boshuisen 2001; Montañés-Rada 2005; Ribeiro 2001).

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (APA 2010; Hirsch 2019). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (WFSBP [Bauer 2013]; Hirsch 2018; Ogle 2013).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of mirtazapine.

Allow 14 days to elapse between discontinuing mirtazapine and initiation of an MAOI.

Dosing: Geriatric

Major depressive disorder (unipolar): Oral: Initial starting doses of 7.5 mg once daily at bedtime have been suggested (VA/DoD 2016). Use with caution; clearance may be reduced; refer to adult dosing. Note: Some experts consider mirtazapine to be useful for stimulating appetite in older adults with depression and weight loss (Ritchie 2018).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, clearance is decreased with moderate and severe renal impairment. Use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, clearance may be decreased with hepatic impairment. Use with caution.

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder (MDD)

Use: Off-Label: Adult

  Headache, chronic tension-type, prophylaxisLevel of Evidence [C]

Data from a limited number of patients studied suggest that mirtazapine may be beneficial for the prophylaxis of chronic tension-type headache Ref.

Based on the EFNS guideline on the treatment of tension-type headache, mirtazapine is probably effective and a second-line option for the prophylaxis of chronic tension-type headache.

  Panic disorderLevel of Evidence [C]

Data from a limited number of patients studied suggest that mirtazapine may be beneficial for the treatment of panic disorder Ref.

Based on the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders, mirtazapine is a second-line treatment option for panic disorder.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Major Depressive Disorder In Adults,” October 2009

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder,” 2015.

Headache, Tension-type:

European Federation of Neurological Societies, “EFNS guideline on the treatment of tension-type headache – Report of an EFNS task force,” 2010

Obsessive-Compulsive Disorder:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder,” 2007

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

Panic Disorder:

Anxiety Disorders Association of Canada (ADAC), “Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders,” 2014

Post Traumatic Stress Disorder (PTSD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” Guideline Watch (March 2009)

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

Administration: Oral

Administer without regard to meals.

Orally disintegrating tablet: Open blister pack and place tablet on the tongue; tablet is formulated to dissolve on the tongue without water; do not split tablet.

Dietary Considerations

Some products may contain phenylalanine.

Storage/Stability

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture. Use orally disintegrating tablets immediately upon opening individual tablet blister; once removed it cannot be stored.

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 fatigue, constipation, dry mouth, increased hunger, weight gain, loss of strength and energy, or nightmares. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of infection, 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), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), flu-like symptoms, mouth irritation, mouth sores, agitation, panic attacks, mood changes, agitation, tachycardia, abnormal heartbeat, severe dizziness, passing out, joint pain, vision changes, eye pain, eye irritation, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (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:
  Geriatric Patients: High-Risk Medication:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Remeron: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089021.pdf

Remeron SolTab: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM289881.pdf

Contraindications

Hypersensitivity to mirtazapine or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either mirtazapine or the MAO inhibitor); initiation of mirtazapine in a patient receiving linezolid or intravenous methylene blue

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Mirtazapine is not FDA approved for use in children.

– The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

– Prescriptions should be written for the smallest quantity consistent with good patient care. The patient’s family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.

Concerns related to adverse effects:

• Akathisia/psychomotor restlessness: Most likely to occur within first few weeks of treatment and characterized by unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. Increasing the dose in these patients may be detrimental.

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is low relative to other antidepressants.

• Arrhythmias: QT prolongation, torsade de pointes, and ventricular fibrillation have been reported (rarely); case reports are mostly associated with mirtazapine overdose (although one case series of single-agent mirtazapine overdose in 84 patients did not identify any cases of QT prolongation [Berling 2014]) or patients with risk factors for QT prolongation or receiving concomitant QT-prolonging agents. Use caution in patients with cardiovascular disease, history of QT prolongation, or receiving concomitant QT-prolonging agents.

• Blood dyscrasias: Discontinue immediately if signs and symptoms of neutropenia/agranulocytosis occur.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). The degree of sedation is moderate to high relative to other antidepressants.

• Dizziness: Dizziness may occur; it is unclear whether or not tolerance may develop to dizziness.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).

• Hyperlipidemia: May increase serum cholesterol and triglyceride levels.

• Hyponatremia: May cause hyponatremia. Use caution in patients at risk, such as elderly or patients concomitantly treated with medications known to cause hyponatremia.

• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Orthostatic hypotension: May cause orthostatic hypotension (risk is low relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, dehydration, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: The incidence of sexual dysfunction with mirtazapine is generally lower than with SSRIs (Bauer 2013).

• Weight gain: May increase appetite and stimulate weight gain.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment. Clinically significant transaminase elevations have been observed.

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder, including details regarding family history of suicide, bipolar disorder, and depression. Mirtazapine is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased with moderate and severe renal impairment.

• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.

Concurrent drug therapy issues:

• 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.

Dosage form specific issues:

• Lactose: Tablets may contain lactose.

• Phenylalanine: SolTab formulation may contain phenylalanine.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

Geriatric Considerations

Mirtazapine can produce marked sedation in the elderly.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011).

Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects.

Pregnancy Considerations

Mirtazapine crosses the placenta (Hatzidaki 2008).

A significant increase in major teratogenic effects has not been observed following exposure to mirtazapine during pregnancy; however, information is limited (Larsen 2015; MacQueen 2016).

Therapy with antidepressants during pregnancy should be individualized (ACOG 92 2008). Psychotherapy or other nonmedication therapies may be considered for some women; however, antidepressant medication should be considered for pregnant women with moderate to severe major depressive disorder (APA 2010). If treatment for MDD is initiated for the first time during pregnancy, agents other than mirtazapine are preferred (Larsen 2015; MacQueen 2016). Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 92 2008; APA 2010; Yonkers 2009).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breast-Feeding Considerations

Mirtazapine and its active metabolite are present in breast milk.

The highest relative infant dose (RID) of mirtazapine reported in the literature is 4.4%. Authors of the study calculated the RID following maternal administration of mirtazapine 22.5 mg/day to a woman at 6 weeks’ postpartum; metabolite concentrations were not evaluated. Breast milk was sampled 4 hours after the maternal dose (Klier 2007). Desmethylmirtazpine can also be detected in breast milk (Kristensen 2007).

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

Mirtazapine can be detected in the serum of breastfed infants; adverse events have generally not been observed, although possible sedation and weight gain was noted in one case report (Kristensen 2007; Smit 2015; Tonn 2009).

Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015). When first initiating an antidepressant in a breastfeeding female, agents other than mirtazapine are preferred (Berle 2011; MacQueen 2016). The manufacturer recommends that caution be used if administered to breastfeeding females.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Frequency not always defined.

>10%:

Central nervous system: Drowsiness (54%)

Endocrine & metabolic: Weight gain (12%; weight gain of >7% reported in 8% of adults, 49% of pediatric patients), increased serum cholesterol (15%)

Gastrointestinal: Xerostomia (25%), increased appetite (17%), constipation (13%)

1% to 10%:

Cardiovascular: Peripheral edema (2%), edema (1%), hypertension, vasodilatation

Central nervous system: Dizziness (7%), abnormal dreams (4%), abnormality in thinking (3%), confusion (2%), agitation, amnesia, anxiety, apathy, depression, hypoesthesia, malaise, myasthenia, paresthesia, twitching, vertigo

Dermatologic: Pruritus, skin rash

Endocrine & metabolic: Increased serum triglycerides (6%), increased thirst

Gastrointestinal: Abdominal pain, anorexia, vomiting

Genitourinary: Urinary frequency (2%), urinary tract infection

Hepatic: Increased serum ALT (≥3 times ULN: 2%)

Neuromuscular & skeletal: Weakness (8%), back pain (2%), myalgia (2%), tremor (2%), arthralgia, hyperkinesia, hypokinesia

Respiratory: Flu-like symptoms (5%), dyspnea (1%), increased cough, sinusitis

<1%, postmarketing, and/or case reports: Abnormal accommodation, abnormal hepatic function tests, abnormal lacrimation, acne vulgaris, ageusia, akathisia, alopecia, altered sense of smell, amenorrhea, anemia, angina pectoris, angle-closure glaucoma, aphasia, aphthous stomatitis, arthritis, asphyxia, asthma, ataxia, atrial arrhythmia, bigeminy, blepharitis, bone fracture, bone marrow depression (granulocytopenia, agranulocytopenia, aplastic anemia), bradycardia, breast engorgement, breast hypertrophy, bronchitis, bullous dermatitis, bursitis, cardiac arrest, cardiomegaly, cellulitis, cerebral ischemia, chest pain, chills, cholecystitis, colitis, conjunctivitis, cystitis, deafness, dehydration, delirium, delusions, dementia, depersonalization, dermal ulcer, diabetes mellitus, diarrhea, diplopia, drug dependence, dysarthria, dyskinesia, dysmenorrhea, dystonia, dysuria, ejaculatory disorder, emotional lability, enlargement of abdomen, enlargement of salivary glands, eosinophilia, epistaxis, eructation, erythema multiforme, euphoria, exfoliative dermatitis, extrapyramidal reaction, eye pain, facial edema, fatigue, fever, gastritis, gastroenteritis, gingival hemorrhage, glaucoma, glossitis, goiter, gout, hallucination, headache, hematuria, hepatic cirrhosis, herpes simplex infection, herpes zoster, hiccups, hostility, hyperacusis, hyperreflexia, hypoesthesia (oral), hyponatremia, hypotension, hypothyroidism, hypotonia, impotence, increased acid phosphatase, increased creatine phosphokinase, increased libido, increased serum AST, insomnia, intestinal obstruction, keratoconjunctivitis, laryngitis, left heart failure, lethargy, leukopenia, leukorrhea, lymphadenopathy, lymphocytosis, manic reaction, mastalgia, menorrhagia, migraine, mouth edema, myocardial infarction, myoclonus, myositis, nausea, neck pain, neck stiffness, nephrolithiasis, nightmares, nystagmus, oral candidiasis, orthostatic hypotension, ostealgia, osteoarthritis, osteoporosis, otalgia, otitis media, pancreatitis, pancytopenia, paralysis, paranoia, petechia, phlebitis, pneumonia, pneumothorax, polyuria, prolonged Q-T interval on ECG, psychomotor agitation, psychoneurosis, psychotic depression, pulmonary embolism, restless leg syndrome, rhabdomyolysis, rupture of tendon, seborrhea, sedation, seizure, serotonin syndrome, sialorrhea, skin hypertrophy, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, stupor, suicidal behavior, suicidal ideation, syncope, tenosynovitis, thrombocytopenia, tongue discoloration, tongue edema, tonic-clonic seizures, torsades de pointes (rare), toxic epidermal necrolysis, ulcer, urethritis, urinary incontinence, urinary retention, urinary urgency, urticaria, uterine hemorrhage, vaginitis, vascular headache, ventricular fibrillation, ventricular premature contractions, ventricular tachycardia, weight loss, withdrawal syndrome, xeroderma

Metabolism/Transport Effects

Substrate of CYP1A2 (major), CYP2C9 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the CNS depressant effect of Mirtazapine. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Alpha2-Agonists: Mirtazapine may diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider therapy modification

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

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

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Mirtazapine. Risk C: Monitor therapy

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

CNS Depressants: May enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

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

CYP1A2 Inducers (Moderate): May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). 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

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). 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

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Risk X: Avoid combination

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

Deferasirox: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

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

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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

FluvoxaMINE: Mirtazapine may enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Mirtazapine. Management: Consider alternatives to this combination when possible. If combined, monitor for increased mirtazapine effects/toxicities and for signs and symptoms of serotonin syndrome. Risk D: Consider therapy modification

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

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

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

Haloperidol: QT-prolonging Agents (Indeterminate Risk – Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

Linezolid: May enhance the serotonergic effect of Mirtazapine. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. Initiation of mirtazapine during linezolid treatment is considered contraindicated. Risk D: Consider therapy modification

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

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

Methylene Blue: Mirtazapine may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

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

Minocycline: May enhance the CNS depressant effect of CNS Depressants. 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

Monoamine Oxidase Inhibitors: May enhance the neurotoxic (central) effect of Mirtazapine. While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Risk X: Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

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

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

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

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk – Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.Risk C: Monitor therapy

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

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

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Tobacco (Smoked): May decrease the serum concentration of Mirtazapine. Risk C: Monitor therapy

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tryptophan: May enhance the serotonergic effect of Mirtazapine. This could result in serotonin syndrome. Risk X: Avoid combination

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.Risk D: Consider therapy modification

Warfarin: Mirtazapine may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Monitoring Parameters

Patients should be monitored for signs of agranulocytosis or severe neutropenia such as sore throat, stomatitis or other signs of infection or a low WBC; renal and hepatic function; mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; signs/symptoms of serotonin syndrome; lipid profile; weight gain

Advanced Practitioners Physical Assessment/Monitoring

Monitor for CNS depression/sedation. Monitor for clinical worsening and suicide ideation. Taper dosage slowly when discontinuing.

Nursing Physical Assessment/Monitoring

Monitor therapeutic response (ie, mood, affect, mental status) at beginning of therapy and periodically throughout. Monitor for CNS depression/sedation. Monitor for clinical worsening and suicide ideation. Taper dosage slowly when discontinuing.

Dosage Forms: US

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

Tablet, Oral:

Remeron: 15 mg, 30 mg [scored]

Remeron: 45 mg [DSC]

Generic: 7.5 mg, 15 mg, 30 mg, 45 mg

Tablet Disintegrating, Oral:

Remeron SolTab: 15 mg, 30 mg, 45 mg [contains aspartame]

Generic: 15 mg, 30 mg, 45 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Remeron: 30 mg

Generic: 15 mg, 30 mg, 45 mg

Tablet Disintegrating, Oral:

Remeron RD: 15 mg, 30 mg, 45 mg [contains ASPARTAME]

Generic: 15 mg, 30 mg, 45 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AX11
Generic Available (US)

Yes

Pricing: US

Tablet, orally-disintegrating (Mirtazapine Oral)

15 mg (per each): $2.36

30 mg (per each): $2.43

45 mg (per each): $2.59

Tablet, orally-disintegrating (Remeron SolTab Oral)

15 mg (per each): $5.10

30 mg (per each): $5.26

45 mg (per each): $5.59

Tablets (Mirtazapine Oral)

7.5 mg (per each): $2.63

15 mg (per each): $2.70 – $2.72

30 mg (per each): $2.77 – $2.80

45 mg (per each): $2.83 – $2.85

Tablets (Remeron Oral)

15 mg (per each): $6.41

30 mg (per each): $6.60

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

Mirtazapine is a tetracyclic antidepressant that works by its central presynaptic alpha2-adrenergic antagonist effects, which results in increased release of norepinephrine and serotonin. It is also a potent antagonist of 5-HT2 and 5-HT3 serotonin receptors and H1 histamine receptors and a moderate peripheral alpha1-adrenergic and muscarinic antagonist; it does not inhibit the reuptake of norepinephrine or serotonin.

Pharmacodynamics/Kinetics

Absorption: Rapid and complete

Protein binding: ~85%

Metabolism: Extensively hepatic via CYP1A2, 2D6, 3A4 and via demethylation and hydroxylation

Bioavailability: ~50%

Half-life elimination: 20 to 40 hours; increased with renal or hepatic impairment

Time to peak, serum: ~2 hours

Excretion: Urine (75%) and feces (15%) as metabolites

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance is reduced ~30% in patients with moderate (CrCl 11 to 39 mL/minute) and ~50% in patients with severe (CrCl <10 mL/minute) renal impairment

Hepatic function impairment: Clearance is decreased ~30% in patients with hepatic impairment

Geriatric: Clearance is reduced 40% in elderly men and 10% in elderly women.

Gender: Women have a longer elimination half-life (37 hours) than men (26 hours).

Local Anesthetic/Vasoconstrictor Precautions

Although mirtazapine is not a tricyclic antidepressant, it results in increased norepinephrine release as part of its mechanisms. It has been suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way, including mirtazapine.

Mirtazapin is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine 2% with Neo-Cobefrin]) be used with caution.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation); rare occurrence of aphthous stomatitis; facial, mouth, tongue edema; glossitis, tongue discoloration. Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

Rare occurrence of gingival hemorrhage.

FDA Approval Date
June 14, 1996
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Brand Names: International

Afloyan (ES); Aurozapine (VN); Avanza (AU, NZ); Avanza Soltab (AU); Axit (AU); Calixta (HR); Ciblex (CL, PY); Comenter (CR, DO, GT, HN, NI, PA, SV); Espirtal (UA); Menelat (PH, TZ); Mi Er Ning (CN); Mirap (IE); Mirastad (HK); Mirazep (IN, LK, PH, UA); Mirez (BD); Miro (IL); Mirta TD (MT); Mirtapan (HK); Mirtapax (CO, EC); Mirtapil (TR); Mirtaz (LK); Mirtazon (AU); Mirtel (UA); Mirtimash (EG); Mirzap (ID); Mitrapil (LK); Norset (FR); Noxibel (EC, PY); Odonazin (HR); Rapine (BD); Reflex (JP); Remergil (DE); Remergon (BE, LU); Remeron (AE, AR, AT, BB, BH, BR, CH, CN, CO, CR, CY, CZ, DK, DO, EC, EE, EG, FI, GR, GT, HN, ID, IL, IQ, IR, IS, IT, JO, JP, KR, KW, LB, LT, LV, LY, MX, MY, NI, NL, NO, OM, PA, PE, PK, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, SY, TR, TW, UY, VE, VN, YE, ZA); Remeron SolTab (CO, HK, PH, SG); Remirta (BG, MT); Remirta OD (HK); Remixil ODT (KR); Resant (BD); Sinmaron (TW); Trazapin (BD); U-Mirtaron (TW); Vastat Flas (ES); Zapimet (EG); Zismirt (IE); Zispin (GB, IE); Zulin (RO)

Mirtazapine (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

(mir TAZ a peen)

Brand Names: US

Remeron; Remeron SolTab

Brand Names: Canada

Remeron; Remeron RD

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in children. Talk with the doctor.
What is this drug used for?
  • It is used to treat low mood (depression).
  • 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 mirtazapine 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 are taking any of these drugs: Diazepam, linezolid, or methylene blue.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • 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.
  • It may take several weeks to see the full effects.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • Low white blood cell counts have rarely happened with this drug. This may lead to a higher chance of getting an infection. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat.
  • An unsafe heartbeat that is not normal (long QT on ECG) has happened with this drug. Sudden deaths have rarely happened in people taking this drug. Talk with the doctor.
  • This drug may cause high cholesterol and triglyceride levels. Talk with the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this drug.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • 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.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Oral-disintegrating tablet:
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
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 low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Flu-like signs.
  • Mouth irritation or mouth sores.
  • Restlessness.
  • A fast heartbeat.
  • A heartbeat that does not feel normal.
  • Very bad dizziness or passing out.
  • Joint pain.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • 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:
  • Feeling sleepy.
  • Dizziness.
  • Constipation.
  • Dry mouth.
  • More hungry.
  • Weight gain.
  • Feeling tired or weak.
  • Strange or odd dreams.
  • 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 products:
  • Take at bedtime if it causes sleepiness.
  • Take with or without food. Take with food if it causes an upset stomach.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Oral-disintegrating tablet:
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place on your tongue and let it dissolve. Water is not needed. Do not swallow it whole. Do not chew, break, or crush it.
  • Do not take this drug out of the blister pack until you are ready to take it. Take this drug right away after opening the blister pack. Do not store the removed drug for future use.
What do I do if I miss a dose?
  • 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.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Protect from light.
  • 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.