MetroNIDAZOLE (Systemic) (Lexi-Drugs)

ALERT: US Boxed Warning
  Carcinogenic:
Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

FDA: https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Metronidazole Injection, USP&st=c

Pronunciation

(met roe NYE da zole)

Brand Names: US

Flagyl

Brand Names: Canada

APO-MetroNIDAZOLE; Auro-MetroNIDAZOLE; Flagyl; NOVO-Nidazol [DSC]; PMS-MetroNIDAZOLE

Dosing: Adult

Amebiasis, intestinal (acute dysentery) or extraintestinal (liver abscess): Oral: 500 to 750 mg every 8 hours for 7 to 10 days followed by an intraluminal agent (eg, paromomycin) (Drugs for Parasitic Infections 2013; Leder 2018a; Leder 2018b)

Bacterial vaginosis: Oral: 500 mg twice daily for 7 days (CDC [Workowski 2015]; SOGC [Yudin 2017])

Balantidiasis (alternative agent) (off-label use): Oral: 750 mg 3 times daily for 5 days (CDC 2013; Drugs for Parasitic Infections 2013; Weller 2018)

Bite wound infection, prophylaxis or treatment, animal or human bite (alternative agent) (off-label use): Oral, IV: 500 mg every 8 hours (Baddour 2018a; Baddour 2018b; IDSA [Stevens 2014]). Duration is 3 to 5 days for prophylaxis; duration of treatment for established infection varies based on patient-specific factors (Baddour 2018a; Baddour 2018b). Note: For animal bites, use in combination with an appropriate agent for Pasteurella multocida. For human bites, use in combination with an appropriate agent for Eikenella corrodens (IDSA [Stevens 2014]).

Clostridioides (formerly Clostridiumdifficile infection (off-label use): Note: Criteria for disease severity is based on expert opinion and should not replace clinical judgment (IDSA/SHEA [McDonald 2018]).

Nonsevere (supportive clinical data: WBC ≤15,000 cells/mm3 and serum creatinine <1.5 mg/dL), initial episode (alternative agent if oral vancomycin or fidaxomicin unavailable or contraindicated): Oral: 500 mg 3 times daily for 10 days. Note: Treatment duration may be extended to 14 days if patient has improved but has not had symptom resolution (IDSA/SHEA [McDonald 2018]).

Fulminant infection (supportive clinical data: ileus, megacolon, and/or hypotension/shock): IV: 500 mg every 8 hours in combination with oral and/or rectal vancomycin (IDSA/SHEA [McDonald 2018]; Surawicz 2013)

Crohn disease, management after surgical resection (off-label use):

Monotherapy: Oral: 20 mg/kg/day (in 3 divided doses) or 1 to 2 g/day in divided doses for 3 months (ACG [Lichtenstein 2018]; Rutgeerts 1995); begin as soon as oral intake is resumed after surgery (Rutgeerts 1995).

Combination therapy: Oral: 250 mg 3 times daily (D’Haens 2008; Lopez-Sanromán 2017) or 1 to 2 g/day in divided doses for 3 months (ACG [Lichtenstein 2018]); begin as soon as oral intake is resumed after surgery and administer in combination with a thiopurine (azathioprine or mercaptopurine) or a TNF-alpha inhibitor (eg, adalimumab) (De Cruz 2015; D’Haens 2008).

Crohn disease, treatment of simple perianal fistulas (off-label use): Oral: 10 to 20 mg/kg/day in divided doses; treat for 4 to 8 weeks with or without ciprofloxacin (ACG [Lichtenstein 2018]).

Dientamoeba fragilis infection (off-label use): Oral: 500 to 750 mg 3 times daily for 10 days (CDC 2012; Nagata 2012)

Giardiasis (alternative agent) (off-label use): Oral: 250 mg 3 times daily or 500 mg 2 times daily for 5 to 7 days (Bartelt 2018; Drugs for Parasitic Infections 2013; Ordonez-Mena 2017)

Helicobacter pylori eradication (off-label use):

Clarithromycin triple regimen: Oral: Metronidazole 500 mg 3 times daily in combination with clarithromycin 500 mg twice daily and a standard-dose or double-dose proton pump inhibitor (PPI) twice daily; continue regimen for 14 days. Note: Avoid use of clarithromycin triple therapy in patients with risk factors for macrolide resistance (eg, prior macrolide exposure, local clarithromycin resistance rates ≥15%) (ACG [Chey 2017]; Fallone 2016).

Bismuth quadruple regimen: Oral: Metronidazole 250 mg 4 times daily or 500 mg 3 or 4 times daily in combination with either bismuth subsalicylate 300 to 524 mg or bismuth subcitrate 120 to 300 mg 4 times daily, tetracycline 500 mg 4 times daily, and a standard-dose PPI twice daily; continue regimen for 10 to 14 days (ACG [Chey 2017]; Fallone 2016).

Concomitant regimen: Oral: Metronidazole 500 mg twice daily in combination with clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and a standard-dose PPI twice daily; continue regimen for 10 to 14 days (ACG [Chey 2017]; Fallone 2016).

Sequential regimen (alternative regimen): Oral: Amoxicillin 1 g twice daily plus a standard-dose PPI twice daily for 5 to 7 days; then follow with clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily, and a standard-dose PPI twice daily for 5 to 7 days (ACG [Chey 2017]); some experts prefer the 10-day sequential regimen (amoxicillin for 5 days, followed by metronidazole and clarithromycin for 5 days) over the 14-day sequential regimen (amoxicillin for 7 days, followed by metronidazole and clarithromycin for 7 days) due to the lack of data showing superiority of the 14-day regimen over the 10-day regimen in North America (ACG [Chey 2017]; Crowe 2018).

Hybrid regimen (alternative regimen): Oral: Amoxicillin 1 g twice daily plus a standard-dose PPI twice daily for 7 days; then follow with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily, and a standard-dose PPI twice daily for 7 days (ACG [Chey 2017]; Wang 2015).

Intra-abdominal infection: Oral, IV: 500 mg every 8 hours as part of an appropriate combination regimen. Duration of therapy is for 4 to 7 days following adequate source control (SIS/IDSA [Solomkin 2010]); for uncomplicated appendicitis and diverticulitis managed nonoperatively, a longer duration is necessary (Barshak 2018; Pemberton 2018). Note:Empiric oral regimens may be appropriate for patients with mild to moderate infection. Other patients may be switched from IV to oral therapy at the same dose when clinically improved and able to tolerate an oral diet (SIS/IDSA [Solomkin 2010]; SIS [Mazuski 2017]).

Intracranial abscess (brain abscess, intracranial epidural abscess): IV: 7.5 mg/kg (usually 500 mg) every 6 to 8 hours for 6 to 8 weeks in combination with other appropriate antimicrobial therapy (Bodilsen 2018; Sexton 2018b; Southwick 2018). Note: May switch IV metronidazole to oral metronidazole at the same dose to complete treatment course (Southwick 2018).

Pelvic inflammatory disease (PID):

Mild to moderate PID: Oral: 500 mg twice daily for 14 days (may be added to a combination of a second- or third-generation parenteral cephalosporin and doxycycline in select women) (CDC [Workowski 2015])

PID with tubo-ovarian abscess, initial therapy (alternative regimen): IV: 500 mg every 8 hours as part of an appropriate combination regimen (Beigi 2018)

PID with tubo-ovarian abscess, oral therapy following clinical improvement on a parenteral regimen: Oral: 500 mg twice daily with doxycycline to complete at least 14 days of therapy (CDC [Workowski 2015])

Periodontitis, generalized aggressive (off-label use): Oral: 250 mg every 8 hours in combination with amoxicillin for 10 to 14 days; used in addition to scaling, root planing, and pocket irrigation (Rabelo 2015; Silva-Senem 2013)

Pneumonia, aspiration (alternative agent): Oral, IV: 500 mg 3 times daily in combination with an appropriate beta-lactam (eg, oral amoxicillin, IV penicillin, or an IV third-generation cephalosporin) for 7 days (Bartlett 2018)

Pouchitis (post ileal pouch-anal anastomosis) (off-label use):

Acute disease (alternative agent): Oral: 500 to 1,000 mg every 12 hours for 14 days (Holubar 2010; Navaneethan 2009; Shen 2018; Wall 2011)

Chronic disease: Oral: 500 mg every 12 hours in combination with ciprofloxacin for at least 28 days (Mimura 2002; Shen 2018)

Skin and soft tissue infections:

Necrotizing infections (as a component of an appropriate combination regimen) (alternative agent): IV: 500 mg every 6 hours. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).

Surgical site infections, incisional (eg, intestinal or GU tract; axilla or perineum), warranting anaerobic coverage: IV: 500 mg every 8 hours in combination with other appropriate agents. Duration depends on severity, need for debridement, and clinical response (IDSA [Stevens 2014]).

Surgical prophylaxis:

IV: 500 mg within 60 minutes prior to surgical incision in combination with other antibiotics. Considered a recommended agent for select procedures involving the GI tract, urologic tract, or head and neck (Bratzler 2013).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. IV: 15 mg/kg 1 hour prior to surgical incision; followed by 7.5 mg/kg 6 and 12 hours after initial dose.

Oral:

Colorectal surgical prophylaxis (off-label use): 1 g every 3 to 4 hours for 3 doses with additional oral antibiotics, starting after mechanical bowel preparation the evening before a morning surgery and followed by an appropriate IV antibiotic prophylaxis regimen (Bratzler 2013).

Uterine evacuation (induced abortion or pregnancy loss) (alternative agent) (off-label use): 1 g as a single dose ≤12 hours before the procedure (ACOG 2018; Shih 2018)

Tetanus (Clostridium tetani infection) (off-label use): Oral, IV: 500 mg every 6 to 8 hours for 7 to 10 days in combination with supportive therapy (Ahmadsyah 1985; Sexton 2018a)

Trichomoniasis (index case and sex partner):

Initial treatment: Oral: 2 g as a single dose or 500 mg twice daily for 7 days (preferred in HIV-infected women) (Adamski 2014; CDC [Workowski 2015]; Howe 2017; Kissinger 2010; Kissinger 2018; SOGC [van Schalkwyk 2015]). Note: Coverage of trichomoniasis, along with other appropriate antimicrobials, is indicated in cases of recurrent or persistent urethritis in men who have sex with women and who live in regions where T. vaginalis is prevalent and for prophylaxis after sexual assault (CDC [Workowski 2015]).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice. Oral: 375 mg twice daily or 250 mg every 8 hours for 7 days or 1 g twice daily for 2 doses.

Persistent or recurrent infection (ie, treatment failure of nitroimidazole [eg, metronidazole] single-dose therapy) (off-label dose): Oral: 500 mg twice daily for 7 days for failure of 2 g single-dose regimen. If this regimen fails, 2 g once daily for 7 days is recommended (CDC [Workowski 2015]).

Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice: Anaerobic infections: IV: 15 mg/kg (1g) loading dose; IV or Oral: 7.5 mg/kg (500 mg) every 6 hours (maximum: 4 g/day).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Manufacturer’s labeling:

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, decreased renal function does not alter the single-dose pharmacokinetics.

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling; metronidazole metabolites may accumulate; monitor for adverse events.

ESRD requiring dialysis: Metronidazole metabolites may accumulate; monitor for adverse events. Accumulated metabolites may be rapidly removed by dialysis:

Intermittent hemodialysis (IHD): If administration cannot be separated from hemodialysis, consider supplemental dose following hemodialysis.

Peritoneal dialysis (PD): No dosage adjustment necessary.

Alternative dosing:

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (50% to 100%): 500 mg every 8 to 12 hours. Note: Dosing regimen highly dependent on clinical indication (trichomoniasis vs C. difficile colitis) (Heintz 2009). Note: Dosing dependent on the assumption of thrice-weekly, complete IHD sessions.

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH/CVVHD/CVVHDF: 500 mg every 6 to 12 hours (or per clinical indication; dosage reduction generally not necessary)

Dosing: Hepatic Impairment: Adult

Manufacturer’s labeling:

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary; use with caution and monitor for adverse events.

Severe impairment (Child-Pugh class C):

Capsules:

Amebiasis: 375 mg 3 times daily

Trichomoniasis: 375 mg once daily

Tablets, injection: Reduce dose by 50%

Alternative dosing: The pharmacokinetics of a single oral 500 mg dose were not altered in patients with cirrhosis; initial dose reduction is therefore not necessary (Daneshmend 1982). In one study of IV metronidazole, patients with alcoholic liver disease (with or without cirrhosis) demonstrated a prolonged elimination half-life (eg, ~18 hours). The authors recommended the dose be reduced accordingly (clearance was reduced by ~62%) and the frequency may be prolonged (eg, every 12 hours instead of every 6 hours) (Lau 1987). In another single IV dose study using metronidazole metabolism to predict hepatic function, patients classified as Child-Pugh class C demonstrated a half-life of ~21.5 hours (Muscara 1995).

Dosing: Pediatric

Note: Some clinicians recommend using adjusted body weight in obese children. Dosing weight = IBW + 0.45 (TBW-IBW)

General dosing, susceptible infection (Red Book [AAP 2018]): Infants, Children, and Adolescents:

Oral: 15 to 50 mg/kg/day in divided doses 3 times daily; maximum daily dose: 2,250 mg/day

IV: 22.5 to 40 mg/kg/day in divided doses 3 or 4 times daily; maximum daily dose: 4,000 mg/day

Amebiasis: Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 7 to 10 days; maximum dose: 750 mg/dose; for severe infection or extraintestinal disease, IV may be necessary (Bradley 2018; Red Book [AAP 2018])

Appendicitis, perforated (divided dosing): Children and Adolescents: IV: 30 mg/kg/day in divided doses 3 times daily (Emil 2003)

Appendicitis, perforated (once-daily dosing): Limited data available: Children and Adolescents: IV: 30 mg/kg/dose once daily in combination with ceftriaxone; maximum reported daily dose: 1,500 mg/day (Yardeni 2013); however, other pediatric trials did not report a maximum; in adult patients, a maximum daily dose of 1,500 mg/day for once-daily dosing is suggested (IDSA [Solomkin 2010]); in pediatric patients, once-daily metronidazole in combination with ceftriaxone has been shown to have similar efficacy as triple-combination therapy with ampicillin, clindamycin, and gentamicin (Fraser 2010; St Peter 2006; St Peter 2008)

Balantidiasis: Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 5 days; maximum dose: 750 mg/dose (Red Book [AAP 2018])

Catheter (peritoneal dialysis); exit-site or tunnel infection: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose 3 times daily. Maximum dose: 500 mg/dose (ISPD [Warady 2012])

Clostridioides (formerly Clostridiumdifficile infection:

Infants: Mild to moderate infection: Oral, IV: 7.5 mg/kg/dose every 6 hours for 10 days (Red Book [AAP 2018])

Children and Adolescents:

Non-severe infection, initial or first recurrence: Oral: 7.5 mg/kg/dose 3 to 4 times daily for 10 days; maximum dose: 500 mg/dose (IDSA/SHEA [McDonald 2018])

Severe/fulminant infection, initial: IV: 10 mg/kg/dose every 8 hours for 10 days; maximum dose: 500 mg/dose; use concomitantly with oral or rectal vancomycin (IDSA/SHEA [McDonald 2018])

Dientamoeba fragilis: Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 10 days; maximum dose: 750 mg/dose (Red Book [AAP 2018])

Giardiasis: Infants, Children, and Adolescents: Oral: 15 to 30 mg/kg/day in divided doses every 8 hours for 5 to 7 days; maximum dose: 250 mg/dose (Bradley 2018; Gardner 2001; Granados 2012; Ross 2013; Red Book [AAP 2018])

Helicobacter pylori infection: Children and Adolescents: Oral: 20 mg/kg/day in 2 divided doses for 10 to 14 days in combination with amoxicillin and proton pump inhibitor with or without clarithromycin; maximum daily dose: 1,000 mg/day (NASPGHAN/ESPGHAN [Koletzko 2011])

Inflammatory bowel disease:

Crohn disease, perianal disease; induction: Children and Adolescents: Oral: 7.5 mg/kg/dose 3 times daily for 6 weeks with or without ciprofloxacin; maximum dose: 500 mg/dose (Sandhu 2010)

Ulcerative colitis, pouchitis, persistent: Children and Adolescents: Oral: 20 to 30 mg/kg/day in divided doses 3 times daily for 14 days with or without ciprofloxacin or oral budesonide; maximum dose: 500 mg/dose (Turner 2012)

Intra-abdominal infection: Infants, Children, and Adolescents: IV: 30 to 40 mg/kg/day in divided doses 3 times daily as part of combination therapy; maximum dose: 500 mg/dose (IDSA [Solomkin 2010])

Pelvic inflammatory disease: Adolescents: Oral: 500 mg twice daily for 14 days; give with doxycycline plus a cephalosporin (CDC [Workowski 2015])

Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]):

Prophylaxis: Gastrointestinal or genitourinary procedures: Infants, Children, and Adolescents: IV: 10 mg/kg once prior to procedure in combination with cefazolin; Maximum dose: 1,000 mg/dose

Treatment: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose 3 times daily. Maximum daily dose: 1,200 mg/day

Prophylaxis against sexually transmitted diseases following sexual assault (CDC [Workowski 2015]): Adolescents: Oral: 2,000 mg as a single dose in combination with azithromycin and ceftriaxone

Surgical prophylaxis: Children and Adolescents: IV: 15 mg/kg as a single dose 30 to 60 minutes prior to procedure; maximum single dose: 500 mg (IDSA/ASHP [Bratzler 2013])

Surgical prophylaxis, colorectal: Children and Adolescents: Oral: 15 mg/kg/dose every 3 to 4 hours for 3 doses, starting after mechanical bowel preparation the afternoon and evening before the procedure, with or without additional oral antibiotics and with an appropriate IV antibiotic prophylaxis regimen; maximum dose: 1,000 mg/dose (IDSA/ASHP [Bratzler 2013])

Tetanus (Clostridium tetani infection): Infants, Children, and Adolescents: IV, Oral: 30 mg/kg/day in divided doses 4 times daily for 7 to 10 days; maximum daily dose: 4,000 mg/day(Red Book [AAP 2018])

Trichomoniasis; treatment: Oral:

Children <45 kg: 45 mg/kg/day in divided doses 3 times daily for 7 days; maximum daily dose: 2,000 mg/day (Red Book [AAP 2018])

Children ≥45 kg and Adolescents: 2,000 mg as a single dose once or 500 mg twice daily for 7 days (CDC [Workowski 2015]; Red Book [AAP 2018])

Vaginosis, bacterial: Oral: Children >45 kg and Adolescents: 500 mg twice daily for 7 days (CDC [Workowski 2015]; Red Book [AAP 2018])

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents:

Manufacturer’s labeling:

Mild, moderate, or severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, decreased renal function does not alter the single-dose pharmacokinetics.

ESRD requiring dialysis: Metronidazole metabolites may accumulate; monitor for adverse events; accumulated metabolites may be rapidly removed by dialysis.

Intermittent hemodialysis (IHD): If administration cannot be separated from hemodialysis, consider supplemental dose following hemodialysis.

Peritoneal dialysis (PD): No dosage adjustment necessary

Alternate dosing: Others have used the following adjustments (Aronoff 2007). Note: Renally adjusted dose recommendations are based on doses of 15 to 30 mg/kg/day divided every 6 to 8 hours.

GFR ≥10 mL/minute/1.73 m2: No adjustment required

GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose every 6 hours

Intermittent hemodialysis (IHD): Extensively removed by hemodialysis: 4 mg/kg/dose every 6 hours

Peritoneal dialysis (PD): Extensively removed by peritoneal dialysis: 4 mg/kg/dose every 6 hours

Continuous renal replacement therapy (CRRT): No adjustment required

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents:

Manufacturer labeling:

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary; use with caution and monitor for adverse events

Severe impairment (Child-Pugh class C):

Immediate release tablets, injection: Reduce dose by 50%

Extended release tablets: Use is not recommended.

Alternate dosing: The pharmacokinetics of a single oral 500 mg dose were not altered in patients with cirrhosis; initial dose reduction is therefore not necessary (Daneshmend 1982). In one study of IV metronidazole, adult patients with alcoholic liver disease (with or without cirrhosis) demonstrated a prolonged elimination half-life (eg, ~18 hours). The authors recommended the dose be reduced accordingly (clearance was reduced by ~62%) and the frequency may be prolonged (eg, every 12 hours instead of every 6 hours) (Lau 1987). In another single IV dose study using metronidazole metabolism to predict hepatic function, patients classified as Child-Pugh class C demonstrated a half-life of ~21.5 hours (Muscara 1995).

Use: Labeled Indications

Amebiasis: Treatment of acute intestinal amebiasis (amebic dysentery) and extraintestinal amebiasis (liver abscess)

Limitations of use: When used for amebic liver abscess, may be used concurrently with percutaneous needle aspiration when clinically indicated.

Anaerobic bacterial infections (caused by Bacteroides spp.including the B. fragilis group):

Bacterial septicemia: Treatment of bacterial septicemia (also caused by Clostridium spp.)

Bone and joint infections: Treatment (adjunctive therapy) of bone and joint infections

CNS Infections: Treatment of CNS infections, including meningitis and brain abscess

Endocarditis: Treatment of endocarditis

Gynecologic infections: Treatment of gynecologic infections including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection (also caused by Clostridium spp., Peptococcus spp., Peptostreptococcus spp., and Fusobacterium spp.)

Intra-abdominal infections: Treatment of intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess (also caused by Clostridium spp., Eubacterium spp., Peptococcus spp., and Peptostreptococcus spp.)

Lower respiratory tract infections: Treatment of lower respiratory tract infections, including pneumonia, empyema, and lung abscess

Skin and skin structure infections: Treatment of skin and skin structure infections (also caused by Clostridium spp., Peptococcus spp., Peptostreptococcus spp., and Fusobacterium spp.)

Surgical prophylaxis (colorectal surgery): Injection: Preoperative, intraoperative, and postoperative prophylaxis to reduce the incidence of postoperative infection in patients undergoing elective colorectal surgery classified as contaminated or potentially contaminated

Trichomoniasis: Treatment of infections caused by Trichomonas vaginalis, including treatment of asymptomatic sexual partners

Use: Off-Label: Adult

  BalantidiasisLevel of Evidence [C, G]

Data from a single case report of one immunocompromised patient with pulmonary infection treated with metronidazole suggest that metronidazole may be beneficial for the treatment of balantidiasis Ref. Clinical experience also suggests the utility of metronidazole in the treatment of balantidiasis Ref.

  Bite wound infection, prophylaxis or treatment (animal and human bites)Level of Evidence [G]

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), metronidazole, in combination with other appropriate agents, is an effective and recommended alternative for treatment of bite wounds.

  Clostridioides (formerly Clostridium) difficile infectionLevel of Evidence [G]

Based on the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guidelines for Clostridioides (formerly Clostridiumdifficile infection, oral metronidazole is an effective and recommended alternative agent for the management of initial episodes of nonsevere (WBC ≤15,000 cells/mm3 and serum creatinine <1.5 mg/dL) C. difficile infections if access to vancomycin or fidaxomicin is limited or use is contraindicated. IV metronidazole is recommended in combination with oral and/or rectal vancomycin for fulminant C. difficile infections, particularly when ileus is present. Metronidazole should not be used for prolonged therapy because of the potential for cumulative and potentially irreversible neurotoxicity; oral metronidazole should not be used for recurrent infections.

  Crohn disease, management after surgical resectionLevel of Evidence [B, G]

Data from a small double-blind, randomized, placebo-controlled trial support the use of metronidazole as management of Crohn disease after surgical resection; in the trial, metronidazole reduced the incidence of endoscopic recurrence and decreased early clinical recurrence rates Ref. Data from 2 randomized, placebo-controlled trials and a meta-analysis suggest that metronidazole alone is of modest benefit in reduction of postoperative recurrence, whereas metronidazole combined with a thiopurine (eg, azathioprine, mercaptopurine) or anti-tumor necrosis factor (anti-TNF) (eg, adalimumab) is moderately effective in reducing recurrence rates Ref.

Based on the American Gastroenterological Association Institute guidelines for the management of Crohn disease after surgical resection, metronidazole is a suggested second-line alternative for patients who are concerned about the adverse effects of first-line therapy (eg, anti-TNFs, thiopurines) and who have a lower risk of recurrence. The American College of Gastroenterology Clinical guideline for the management of Crohn disease in adults also suggests that metronidazole may be used following small intestine resection in patients with Crohn disease to prevent recurrence Ref.

  Crohn disease, treatment of simple perianal fistulasLevel of Evidence [G]

Based on the American College of Gastroenterology guidelines for the management of Crohn disease in adults, metronidazole (with or without ciprofloxacin) is an effective and recommended treatment for patients with simple perianal fistulas Ref.

  Dientamoeba fragilis infectionLevel of Evidence [G]

Based on the Centers for Disease Control and Prevention (CDC) resources for health professionals, metronidazole is an effective and recommended agent for the treatment of D. fragilis.

  GiardiasisLevel of Evidence [A, G]

In a meta-analysis of trials evaluating the treatment of giardiasis, the use of metronidazole was found to be of similar effectiveness to albendazole for the treatment of giardiasis, although metronidazole may have slightly more adverse effects Ref.

  Helicobacter pylori eradicationLevel of Evidence [G]

Based on the American College of Gastroenterology guideline on the treatment of Helicobacter pylori infection, metronidazole is an effective and recommended component of a multiple-drug regimen for the treatment of H. pylori infection.

  Periodontitis, generalized aggressiveLevel of Evidence [B]

Data from a small randomized, 12-month, double-blind, placebo-controlled trial (N=35) evaluating the use of either amoxicillin and metronidazole or placebo in conjunction with aggressive dental care demonstrated that amoxicillin (in combination with metronidazole) significantly improved dental parameters and increased beneficial bacteria Ref. In addition, data from a meta-analysis support the use of metronidazole (with or without amoxicillin) for the treatment of aggressive periodontitis Ref.

  Pouchitis (post ileal pouch-anal anastomosis)Level of Evidence [A]

In a systematic review of available clinical trials evaluating the treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis, metronidazole was found to be less effective than ciprofloxacin but as effective as budesonide enemas for inducing remission in acute pouchitis. Metronidazole is considered an effective alternative treatment for this condition Ref.

Data from a noncomparative cohort study suggest that metronidazole, in combination with ciprofloxacin, may be beneficial for the treatment of patients with chronic pouchitis Ref.

  TetanusLevel of Evidence [B, G]

Data from an open-label clinical trial in patients with moderate tetanus treated with either metronidazole or intramuscular procaine penicillin suggest that metronidazole may be beneficial and possibly superior to the use of penicillin for the treatment of this condition Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Clostridioides (Formerly Clostridiumdifficile Infection

American College of Gastroenterology (ACG), “Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections,” April 2013

European Society of Clinical Microbiology and Infectious Diseases (ESCMID), “Update of the Treatment Guidance Document for Clostridium difficile infection,” March 2014

IDSA/SHEA, “Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children,” February 2018

Crohn Disease:

American College of Gastroenterology, “Management of Crohn’s Disease after Surgical Resection,” January 2017

“Management of Crohn’s Disease in Adults,” February 2009

Dyspepsia:

ACG/CAG “Guidelines for the Management of Dyspepsia,” June 2017

“Guidelines for the Management of Dyspepsia,” October 2005

Helicobacter pylori Infection:

“ACG Guideline on the Management of Helicobacter pylori Infection,” August 2007

ACG Guideline on the Treatment of Helicobacter pylori Infection,” February 2017

Intra-abdominal Infection:

Infectious Diseases Society of America (IDSA), “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children,” January 2010

Opportunistic Infections:

DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children, November 2013

DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, October 2014 [Note: Information contained within this monograph is pending revision based on these more recent guidelines]

Osteomyelitis, Native Vertebral:

IDSA, “Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults,” 2015

Sexually Transmitted Disease:

CDC, “Sexually Transmitted Diseases Treatment Guidelines,” June 2015.

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014.

Surgical Prophylaxis:

ASHP, “Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery,” February 2013

Administration: IV

Infuse intravenously over 30 to 60 minutes. Avoid contact of drug solution with equipment containing aluminum.

Administration: Injectable Detail

pH: 4.5 to 7 (ready to use)

Administration: Oral

Administer with food to minimize stomach upset.

Administration: Pediatric

Oral:

Immediate-release tablets and capsules: May administer with food to minimize GI upset

Extended release: Should be taken on an empty stomach (1 hour before or 2 hours after meals); do not split, chew, or crush.

Parenteral: IV: Administer undiluted (5 mg/mL) by slow intermittent infusion over 30 to 60 minutes. Avoid contact of drug solution with equipment containing aluminum.

Dietary Considerations

Take with food to minimize stomach upset.

Sodium: Injectable dosage form may contain sodium.

Ethanol: Use of ethanol is contraindicated during therapy and for 3 days after therapy discontinuation.

Storage/Stability

Oral: Store at 15°C to 25°C (59°F to 77°F). Protect the tablets from light.

Injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Avoid excessive heat. Do not refrigerate. Do not remove unit from overwrap until ready for use. Discard unused solution.

Compatibility

See Trissel’s IV Compatibility Database

Extemporaneously Prepared

Note: A metronidazole suspension (50 mg/mL or 100 mg/mL) is commercially available as a compounding kit.

50 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)

A 50 mg/mL oral suspension may be made with tablets and a 1:1 mixture of Ora-Sweet and Ora-Plus. Crush twenty-four 250 mg tablets in a mortar and reduce to a fine powder. Add small portions of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental portions 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”. Stable for 60 days at room temperature or refrigerated (Allen 1996).

Allen LV Jr, Erickson MA 3rd. Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride, and spironolactone in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53(17):2073-2078.[PubMed 8870895]

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 nausea, vomiting, diarrhea, constipation, lack of appetite, abdominal cramps, abdominal pain, fatigue, muscle pain, joint pain, muscle spasm, decreased libido, injection site irritation, or metallic taste. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), involuntary eye movements, angina, tachycardia, abnormal heartbeat, shortness of breath, bruising, bleeding, swelling of arms or legs, signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), change in balance, dizziness, passing out, headache, difficulty speaking, seizures, thrush, vaginitis, vision changes, irritability, depression, confusion, loss of strength or energy, insomnia, burning or numbness feeling, or signs of aseptic meningitis (headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to lights, fatigue, or confusion) (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:
Contraindications

Hypersensitivity to metronidazole, nitroimidazole derivatives, or any component of the formulation; pregnant patients (first trimester) with trichomoniasis; use of disulfiram within the past 2 weeks; use of alcohol or propylene glycol-containing products during therapy or within 3 days of therapy discontinuation

Canadian labeling: Additional contraindications (not in the US labeling): Active neurological disorders; history of blood dyscrasia; hypothyroidism; hypoadrenalism

Warnings/Precautions

Concerns related to adverse effects:

• Carcinogenic: [US Boxed Warning]: Possibly carcinogenic based on animal data. Reserve use for conditions described in Use; unnecessary use should be avoided.

• CNS effects: Severe neurological disturbances, including aseptic meningitis (may occur within hours of a dose), cerebellar symptoms (ataxia, dizziness, dysarthria), convulsive seizures, encephalopathy, optic neuropathy, and peripheral neuropathy (usually of sensory type and characterized by numbness or paresthesia of an extremity) have been reported. CNS symptoms and CNS lesions are generally reversible within days to weeks of discontinuation of therapy; peripheral neuropathy symptoms may be prolonged after discontinuation. Avoid repeated or prolonged courses due to risk of cumulative neurotoxicity (IDSA/SHEA [McDonald 2018]). Monitor for neurologic symptoms and discontinue therapy if any abnormal neurologic symptoms occur.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Candidiasis infection (known or unknown) may be more prominent during metronidazole treatment, antifungal treatment required.

Disease-related concerns:

• Blood dyscrasias: Use with caution in patients with or history of blood dyscrasias; agranulocytosis, leukopenia, and neutropenia have occurred. Monitor CBC with differential at baseline, during and after treatment.

• Cockayne syndrome: Severe hepatotoxicity/acute hepatic failure (has been fatal) has been reported with systemic metronidazole in patients with Cockayne syndrome; onset is rapid after initiation of treatment. Use metronidazole only after risk vs benefit assessment and if there are no appropriate alternatives in patients with Cockayne syndrome. Obtain LFTs prior to treatment initiation, within the first 2 to 3 days of initiation, frequently during therapy, and after treatment is complete. Discontinue treatment if elevated LFTs occur and monitor until LFTs return to baseline.

• Hepatic impairment: Use with caution in patients with hepatic impairment due to potential accumulation; dosage adjustment recommended in patients with severe hepatic impairment.

• Renal impairment: Use with caution in patients with severe renal impairment or ESRD due to potential accumulation. Accumulated metabolites may be rapidly removed by hemodialysis; supplemental doses may be needed.

• Seizure disorder: Use with caution in patients with a history of seizure disorder.

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:

• Injection: Use injection with caution in patients with heart failure, edema, or other sodium-retaining states, including corticosteroid treatment due to high sodium content. In patients receiving continuous nasogastric secretion aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels.

Other warnings/precautions:

• Ethanol use: Abdominal cramps, nausea, vomiting, headaches, and flushing have been reported with oral and injectable metronidazole and concomitant alcohol consumption (disulfiram-like reactions); avoid alcoholic beverages or products containing propylene glycol during oral or injectable therapy and for at least 3 days after therapy.

Geriatric Considerations

Adjust dose based on renal function.

Pregnancy Considerations

Metronidazole crosses the placenta. Cleft lip with or without cleft palate has been reported following first trimester exposure to metronidazole; however, most studies have not shown an increased risk of congenital anomalies or other adverse events to the fetus following maternal use during pregnancy. Because metronidazole was carcinogenic in some animal species, concern has been raised whether metronidazole should be used during pregnancy. Available studies have not shown an increased risk of infant cancer following metronidazole exposure during pregnancy; however, the ability to detect a signal for this may have been limited.

Metronidazole pharmacokinetics are similar between pregnant and nonpregnant patients (Amon 1981; Visser 1984; Wang 2011).

Bacterial vaginosis and vaginal trichomoniasis are associated with adverse pregnancy outcomes and metronidazole is recommended for the treatment of symptomatic pregnant patients. The dose of oral metronidazole for the treatment of bacterial vaginosis during pregnancy is the same as the CDC recommended twice daily dose in nonpregnant females. When treating vaginal trichomoniasis, the CDC recommends the single oral dose regimen in pregnancy. Although use of metronidazole for vaginal trichomoniasis during the first trimester is contraindicated by the manufacturer; available guidelines note treatment can be given at any stage of pregnancy (CDC [Workowski 2015]).

Metronidazole may also be used for the treatment of giardiasis in pregnant women (some sources recommend second and third trimester administration only) (Gardner 2001; HHS [OI adult 2017]) and symptomatic amebiasis during pregnancy (HHS [OI adult 2017]; Li 1996). Short courses may be used for the treatment of pouchitis or perianal disease in pregnant women with inflammatory bowel disease (avoid use in the first trimester) (van der Woude 2015).The use of other agents is preferred when treatment is needed during pregnancy for Clostridioides (formerly Clostridiumdifficile (Surawicz 2013). Consult current recommendations for appropriate use in pregnant women.

Breast-Feeding Considerations

Metronidazole and its active hydroxyl metabolite are present in breast milk at concentrations similar to maternal plasma concentrations.

The relative infant dose (RID) of metronidazole is 13.7% to 22.9% when calculated using the highest average breast milk concentration reported and compared to an oral infant therapeutic dose of 30 to 50 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Using the highest average milk concentration (45.8 mcg/mL), the estimated daily infant dose via breast milk is 6.87 mg/kg/day. This milk concentration was obtained following a single maternal dose of oral metronidazole 2,000 mg; the authors estimated the infant would have been exposed to metronidazole 21.8 mg over the first 24 hours after the dose (Erickson 1981).

The highest average milk concentration occurred 2 to 4 hours after a single oral maternal dose; the half-life in breast milk was ~9 to 10 hours (Erickson 1981). Metronidazole and its active metabolite can be detected in the serum of breastfeeding infants (Gray 1961; Heisterberg 1983; Passmore 1988).

Loose stools, oral and perianal Candida growth, and oral thrush have been reported in breastfeeding infants exposed to metronidazole (Passmore 1988)

The manufacturer warns of the risk of carcinogenicity in patients exposed to metronidazole based on animal studies; theoretically, this risk is also present in breastfeeding infants exposed to metronidazole via breast milk. Therefore, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. Some guidelines note if metronidazole is given, breastfeeding should be withheld for 12 to 24 hours after a single dose (CDC [Workowski 2015]; WHO 2002); alternatively, the mother may pump and discard breast milk for 24 hours after taking the last metronidazole dose. Breastfeeding should be avoided in women requiring treatment with metronidazole for inflammatory bowel disease (van der Woude 2015). Use of other agents is preferred when treating breastfeeding women for Clostridioides (formerly Clostridiumdifficile infection (Surawicz 2013).

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

>10%:

Central nervous system: Headache (18%)

Gastrointestinal: Nausea (10% to 12%)

Genitourinary: Vaginitis (15%)

1% to 10%:

Central nervous system: Metallic taste (9%), dizziness (4%)

Dermatologic: Genital pruritus (5%)

Gastrointestinal: Abdominal pain (4%), diarrhea (4%), xerostomia (2%)

Genitourinary: Dysmenorrhea (3%), urine abnormality (3%), urinary tract infection (2%)

Infection: Bacterial infection (7%), candidiasis (3%)

Respiratory: Flu-like symptoms (6%), upper respiratory tract infection (4%), pharyngitis (3%), sinusitis (3%)

Frequency not defined:

Cardiovascular: Chest pain, facial edema, flattened T-wave on ECG, flushing, palpitations, peripheral edema, syncope, tachycardia

Central nervous system: Aseptic meningitis, ataxia, brain disease, cerebral lesion (reversible), chills, confusion, convulsions, depression, disulfiram-like reaction (with alcohol), drowsiness, dysarthria, hypoesthesia, insomnia, irritability, malaise, numbness, paresthesia, peripheral neuropathy, psychosis, seizure, vertigo

Dermatologic: Erythematous rash, hyperhidrosis, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Decreased libido

Gastrointestinal: Abdominal cramps, abdominal distress, anorexia, constipation, decreased appetite, dysgeusia, glossitis, hairy tongue, pancreatitis (rare), proctitis, stomatitis, vomiting

Genitourinary: Cystitis, dark urine (rare), dyspareunia, dysuria, urinary incontinence, urine discoloration, vaginal dryness, vulvovaginal candidiasis

Hematologic & oncologic: Agranulocytosis, eosinophilia, leukopenia, neutropenia (reversible), thrombocytopenia (reversible, rare)

Hepatic: Increased liver enzymes, jaundice, severe hepatotoxicity (patients with Cockayne syndrome)

Hypersensitivity: Anaphylaxis, hypersensitivity

Immunologic: DRESS syndrome, serum sickness-like reaction (joint pains)

Local: Inflammation at injection site (IV), injection site reaction

Neuromuscular & skeletal: Arthralgia, muscle spasm, myalgia, weakness

Ophthalmic: Abnormal eye movements (saccadic), nystagmus, optic neuropathy

Renal: Polyuria

Respiratory: Dyspnea, nasal congestion, rhinitis

Miscellaneous: Fever

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2A6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;Inhibits CYP2C9 (weak)

Drug Interactions 

Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Busulfan: MetroNIDAZOLE (Systemic) may increase the serum concentration of Busulfan. Management: The toxic effects of busulfan may be greatly increased with concomitant use of metronidazole. This combination should probably be avoided when possible. If these agents must be used together, increased monitoring for busulfan toxicity is recommended.Risk D: Consider therapy modification

Capecitabine: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Capecitabine. Risk C: Monitor therapy

Carbocisteine: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Carbocisteine. Specifically, metronidazole may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Risk X: Avoid combination

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Disulfiram: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid combination

Dronabinol: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Dronabinol. Specifically, metronidazole may produce severe intolerance to the alcohol contained in the dronabinol oral solution. Risk D: Consider therapy modification

Floxuridine: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Floxuridine. Specifically, serum concentrations of fluorouracil may be increased. Risk C: Monitor therapy

Fluorouracil (Systemic): MetroNIDAZOLE (Systemic) may increase the serum concentration of Fluorouracil (Systemic). Risk C: Monitor therapy

Fosphenytoin: May decrease the serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Lithium: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Lithium. MetroNIDAZOLE (Systemic) may increase the serum concentration of Lithium. Risk C: Monitor therapy

Lopinavir: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Lopinavir. Specifically, the combination of metronidazole and lopinavir/ritonavir solution, which contains 42% alcohol, may result in a disulfiram-like reaction. MetroNIDAZOLE (Systemic) may enhance the arrhythmogenic effect of Lopinavir. Management: Avoid the concomitant use of lopinavir/ritonavir and metronidazole if possible. If these agents are used concomitantly, monitor for QTc prolongation/arrhythmia and if the lopinavir/ritonavir solution is used, development of a disulfiram-like reaction. Risk D: Consider therapy modification

Mebendazole: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased.Risk X: Avoid combination

Mycophenolate: MetroNIDAZOLE (Systemic) may decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy

PHENobarbital: May decrease the serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor therapy

Phenytoin: May decrease the serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase the serum concentration of Phenytoin. Risk C: Monitor therapy

Primidone: May decrease the serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor therapy

Products Containing Propylene Glycol: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur.Risk X: Avoid combination

Ritonavir: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Specifically, the combination of ritonavir oral solution or ritonavir soft gelatin capsule, both of which contain alcohol, and metronidazole may result in a disulfiram-like reaction. Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tegafur: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Tegafur. Risk C: Monitor therapy

Tipranavir: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification

Vecuronium: MetroNIDAZOLE (Systemic) may enhance the neuromuscular-blocking effect of Vecuronium. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): MetroNIDAZOLE (Systemic) may increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives to concomitant therapy with these agents. If concomitant therapy cannot be avoided, consider reducing the dose of the vitamin K antagonist and monitor for increased INR/bleeding. Risk D: Consider therapy modification

Food Interactions

Peak antibiotic serum concentration lowered and delayed, but total drug absorbed not affected.

Test Interactions

May interfere with AST, ALT, triglycerides, glucose, and LDH testing

Monitoring Parameters

Monitor CBC with differential at baseline, during, and after prolonged or repeated courses of therapy. Monitor LFTs in patients with Cockayne syndrome. Closely monitor elderly patients and patients with severe hepatic impairment or ESRD for adverse reactions. Observe patients carefully if neurologic symptoms occur and consider discontinuation of therapy.

Advanced Practitioners Physical Assessment/Monitoring

Assess results of culture and sensitivity tests prior to beginning therapy. Obtain CBC with differential at baseline, during, and after prolonged therapy or repeated courses. Assess elderly patients, patients with ESRD, and patients with severe hepatic impairment closely for adverse reactions. Patients on hemodialysis may need supplemental doses if dose cannot be separated from hemodialysis. Assess patient for peripheral neuropathy or seizure activity; discontinue drug if abnormal neurologic signs develop. Assess for effectiveness of treatment. Test for C. difficile if patient develops diarrhea. Assess if patient regularly consumes alcohol or has consumed it within three days of starting treatment. Avoid prolonged courses of treatment due to risk of neurotoxicity.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Teach patient importance of avoiding alcohol during therapy. Monitor for improvement with infection. Monitor patient for numbness or paresthesia of extremities, seizures, or other CNS abnormalities; instruct patient to report. Counsel hemodialysis patients to take medicine after their sessions on dialysis days rather than in the morning.

Dosage Forms Considerations

Parenteral solution contains 28 mEq of sodium/gram of metronidazole.

First-Metronidazole and MetroNIDAZOLE Benzo+SyrSpend oral suspensions are a compounding kits. Refer to manufacturer’s labeling for compounding instructions.

Dosage Forms: US

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

Capsule, Oral:

Flagyl: 375 mg

Generic: 375 mg

Solution, Intravenous:

Generic: 500 mg (100 mL); 5 mg/mL (100 mL)

Tablet, Oral:

Flagyl: 250 mg, 500 mg

Generic: 250 mg, 500 mg

Dosage Forms: Canada

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

Capsule, Oral:

Flagyl: 500 mg [contains BRILLIANT BLUE FCF (FD&C BLUE #1), FD&C YELLOW #10 (QUINOLINE YELLOW)]

Generic: 500 mg

Solution, Intravenous:

Flagyl: 5 mg/mL (100ml)

Generic: 5 mg/mL (100ml)

Tablet, Oral:

Generic: 250 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • A01AB17
  • J01XD01
  • P01AB01
Generic Available (US)

Yes

Pricing: US

Capsules (Flagyl Oral)

375 mg (per each): $14.35

Capsules (metroNIDAZOLE Oral)

375 mg (per each): $12.29

Solution (metroNIDAZOLE in NaCl Intravenous)

500 mg/100 mL 0.74% (per mL): $0.03

500 mg/100 mL 0.79 (per mL): $0.01 – $0.06

Solution (metroNIDAZOLE Intravenous)

5 mg/mL (per mL): $0.03

Tablets (Flagyl Oral)

250 mg (per each): $10.31

500 mg (per each): $18.41

Tablets (metroNIDAZOLE Oral)

250 mg (per each): $0.25 – $0.58

500 mg (per each): $0.23 – $0.69

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

After diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms

Pharmacodynamics/Kinetics

Absorption: Oral: Well absorbed

Distribution: To bile, seminal fluid, bone, liver, and liver abscesses, lung and vaginal secretions; crosses blood-brain barrier; saliva and CSF concentrations similar to those in plasma

Protein binding: <20%

Metabolism: Hepatic (30% to 60%) to several metabolites including an active hydroxyl metabolite which maintains activity ~30% to 65% of the parent compound (Lamp 1999)

Half-life elimination:

Neonates <7 days (Jager-Roman 1982): Within first week of life, more prolonged than with lower GA:

GA 28 to 30 weeks: 75.3 ± 16.9 hours

GA 32 to 35 weeks: 35.4 ± 1.5 hours

GA 36 to 40 weeks: 24.8 ± 1.6 hours

Neonates ≥7 days: ~22.5 hours (Upadhyaya 1988)

Children and Adolescents: 6 to 10 hours (Lamp 1999)

Adults: ~8 hours

Time to peak, serum: Oral: 1 to 2 hours

Excretion: Urine (unchanged drug and metabolites: 60% to 80%; ~20% of total as unchanged drug); feces (6% to 15%)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: CrCl ≤65 mL/minute: Half-life: 18 to 32 hours (hydroxy metabolite [active]) (Lamp 1999)

Hepatic function impairment: Half-life: 18.31 hours (mean) in one study (Lau 1987)

According to Child-Pugh classification (Muscara 1995):

Child-Pugh class A: ~10.7 hours

Child-Pugh class B: ~13.5 hours

Child-Pugh class C: ~21.5 hours

Dental Use

Treatment of oral soft tissue infections due to anaerobic bacteria including all anaerobic cocci, anaerobic gram-negative bacilli (Bacteroides), and gram-positive spore-forming bacilli (Clostridium). Useful as single agent or in combination with amoxicillin, amoxicillin/clavulanic acid, or ciprofloxacin in the treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans (AA). In aggressive periodontitis, greatest benefit is seen after 3 months of therapy. No benefit was seen after 6 months of therapy (Varela 2011).

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Infrequent occurrence of unusual/metallic taste, xerostomia (normal salivary flow resumes upon discontinuation), sinusitis, bacterial infection, and candidiasis; Rare occurrence of hairy tongue, dysgeusia, glossitis, stomatitis, and syncope.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Anaerobic infections/abscess: Adults: Oral, IV: 500 mg every 6-8 hours, not to exceed 4 g/day

Periodontitis treatment (monotherapy or combination) associated with the presence of Actinobacillus actinomycetemcomitans (AA): Adults: Oral: 250-500 mg every 8 hours for 8-10 days used in addition to scaling and root planing (Varela 2011)

Index Terms

Benzoyl Metronidazole; Flagyl; Metronidazole Benzoate; Metronidazole Hydrochloride

FDA Approval Date
July 18, 1963
References

Adamski A, Clark RA, Mena L, et al. The influence of ART on the treatment of Trichomonas vaginalis among HIV-infected women. Clin Infect Dis. 2014;59(6):883-887. doi: 10.1093/cid/ciu401.[PubMed 24917661]

Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J. 1985;291(6496):648-650.[PubMed 3928066]

Allen LV Jr, Erickson MA 3rd. Stability of Ketoconazole, Metolazone, Metronidazole, Procainamide Hydrochloride, and Spironolactone in Extemporaneously Compounded Oral Liquids. Am J Health Syst Pharm. 1996;53(17):2073-2078.

American Academy of Pediatrics (AAP). Guidelines for Treatment of Sexually Transmitted Infections. American Academy of Pediatrics. 2015.[PubMed AAP.2015]

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 195: Prevention of infection after gynecologic procedures. Obstet Gynecol. 2018;131(6):e172-e189. doi: 10.1097/AOG.0000000000002670.[PubMed 29794678]

Amon I, Amon K, Franke G, et al. Pharmacokinetics of metronidazole in pregnant women. Chemotherapy. 1981;27(2):73-79.[PubMed 7471904]

Anagyrou K, Petrikkos GL, Suller MT, et al. Pulmonary Balantidium coli infection in a leukemic patient. Am J Hematol. 2003;73(3):180-183.[PubMed 12827655]

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]

Aronoff GR, Bennett WM, Berns JS, et al. Drug prescribing in renal failure: dosing guidelines for adults and children. 5th ed. Philadelphia, PA: American College of Physicians; 2007.

Baddour LM. Soft tissue infections due to human bites. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 3, 2018a.

Baddour LM. Soft tissue infections due to dog and cat bites. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 3, 2018b.

Barshak MB. Antimicrobial approach to intra-abdominal infections in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 2, 2018.

Bartelt LA. Giardiasis: treatment and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 3, 2018.

Bartlett JG. Aspiration pneumonia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 1, 2018.

Beigi RH. Management and complications of tubo-ovarian abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 2, 2018.

Bodilsen J, Brouwer MC, Nielsen H, Van De Beek D. Anti-infective treatment of brain abscess. Expert Rev Anti Infect Ther. 2018;16(7):565-578. doi: 10.1080/14787210.2018.1489722.[PubMed 29909695]

Bradley JS, Nelson JD, Barnett E, et al. Nelson’s Pediatric Antimicrobial Therapy. 23rd ed. American Academy of Pediatrics; 2017

Bratzler DW, Dellinger EP, Olsen KM, et al; American Society of Health-System Pharmacists; Infectious Diseases Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283.[PubMed 23327981]

Centers for Disease Control and Prevention (CDC). Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590-594.[PubMed 22874837]

Centers for Disease Control and Prevention (CDC). Parasites – Dientamoeba fragilis: Resources for Health Professionals. http://www.cdc.gov/parasites/dientamoeba/health_professionals/index.html. Updated December 12, 2012. Accessed April 10, 2014.

Centers for Disease Control and Prevention (CDC). Parasites – Balantidiasis: Resources for Health Professionals. https://www.cdc.gov/parasites/balantidium/health_professionals/index.html. Updated January 10, 2013. Accessed July 25, 2018.

Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection [published correction appears in Am J Gastroenterol. 2018;113(7):1102]. Am J Gastroenterol. 2017;112(2):212-239. doi: 10.1038/ajg.2016.563.[PubMed 28071659]

Crowe SE. Treatment regimens for Helicobacter pylori. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 21, 2018.

D’Haens GR, Vermeire S, Van Assche G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn’s disease: a controlled randomized trial. Gastroenterology. 2008;135(4):1123-1129. doi: 10.1053/j.gastro.2008.07.010.[PubMed 18727929]

Daneshmend TK, Homeida M, Kaye CM, Elamin AA, Roberts CJ. Disposition of oral metronidazole in hepatic cirrhosis and in hepatosplenic schistosomiasis. Gut. 1982;23(10):807-813.[PubMed 7117899]

De Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: a randomised trial. Lancet. 2015;385(9976):1406-1417. doi: 10.1016/S0140-6736(14)61908-5.[PubMed 25542620]

Drugs for Parasitic Infections. Treat Guidel Med Lett. 2013;11(suppl):e1-e31.

Eisenberg L, Suchow R, Coles RS, et al. The effects of metronidazole administration on clinical and microbiologic parameters of periodontal disease. Clin Prev Dent. 1991;13(1):28-34.[PubMed 1860284]

Emil S, Laberge JM, Mikhail P, et al. Appendicitis in children: a ten-year update of therapeutic recommendations. J Pediatr Surg. 2003;38(2):236-242.[PubMed 12596112]

Erickson SH, Oppenheim GL, Smith GH. Metronidazole in breast milk. Obstet Gynecol. 1981;57(1):48-50.[PubMed 7454176 ]

Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016;151(1):51-69.e14.[PubMed 27102658]

Flagyl (metronidazole) [prescribing information]. New York, NY: Pfizer; January 2018.

Flagyl capsules (metronidazole) [prescribing information]. New York, NY: Pfizer; May 2017.

Flagyl (metronidazole) [product monograph]. Pointe-Claire, Quebec, Canada: Odan Laboratories LTD; January 2018.

Fraser JD, Aguayo P, Leys CM, et al. A complete course of intravenous antibiotics vs a combination of intravenous and oral antibiotics for perforated appendicitis in children: a prospective, randomized trial. J Pediatr Surg. 2010;45(6):1198-1202.[PubMed 20620320]

Gardner TB, Hill DR. Treatment of giardiasis. Clin Microbiol Rev. 2001;14(1):114-128.[PubMed 11148005 ]

Granados CE, Reveiz L, Uribe LG, Criollo CP. Drugs for treating giardiasis. Cochrane Database Syst Rev. 2012;12:CD007787.[PubMed 23235648]

Gray MS, Kane PO, Squires S. Further observations on metronidazole (Flagyl). Br J Vener Dis. 1961;37:278-279. doi: 10.1002/14651858.CD007787.pub2.[PubMed 13901320]

Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577.[PubMed 19397464]

Heisterberg L, Branebjerg PE. Blood and milk concentrations of metronidazole in mothers and infants. J Perinat Med. 1983; 11(2):114-120.[PubMed 6854509]

HHS Panel on Opportunistic Infections (OI) in HIV-Infected Adults and Adolescents. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations From CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America. Accessed October 23, 2017. Available at http://www.aidsinfo.nih.gov/contentfiles/adult_oi.pdf

HHS Panel on Opportunistic Infections (OI) in HIV-Infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). April 2015. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf

Holubar SD, Cima RR, Sandborn WJ, Pardi DS. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev. 2010; 6:CD001176. doi:10.1002/14651858.CD001176.pub2.[PubMed 20556748]

Howe K, Kissinger PJ. Single-dose compared with multidose metronidazole for the treatment of trichomoniasis in women: a meta-analysis. Sex Transm Dis. 2017;44(1):29-34. doi: 10.1097/OLQ.0000000000000537.[PubMed 27898571]

Ingham HR, Slekon JB, Roxby CM. Bacteriological study of otogenic cerebral abscesses: chemotherapeutic role of metronidazole. Br Med J. 1977;2(6093):991-993.[PubMed 922400]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jacobs DO. Clinical practice. Diverticulitis. N Engl J Med. 2007;357(20):2057-2066.[PubMed 18003962]

Jager-Roman E, Doyle PE, Baird-Lambert J, Cvejic M, Buchanan N. Pharmacokinetics and tissue distribution of metronidazole in the new born infant. J Pediatr. 1982;100(4):651-654.[PubMed 7062220]

Kimberlin DW, Brady MT, Jackson MA, Long SS, eds; Committee on Infectious Diseases; American Academy of Pediatrics. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.

Kissinger P, Mena L, Levison J, et al. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women. J Acquir Immune Defic Syndr. 2010;55(5):565-571. doi: 10.1097/QAI.0b013e3181eda955.[PubMed 21423852]

Kissinger P, Muzny CA, Mena LA, et al. Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial. Lancet Infect Dis. 2018. pii: S1473-3099(18)30423-30427. doi: 10.1016/S1473-3099(18)30423-7.[PubMed 30297322]

Koletzko S, Jones NL, Goodman KJ, et al; H pylori Working Groups of ESPGHAN and NASPGHAN. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children. J Pediatr Gasroenterol Nutr. 2011;53(2):230-243.[PubMed 21558964]

Lamp KC, Freeman CD, Klutman NE, et al, “Pharmacokinetics and Pharmacodynamics of the Nitroimidazole Antimicrobials,” Clin Pharmacokinet, 1999, 36(5):353-73.[PubMed 10384859]

Lau AH, Evans R, Chang CW, Seligsohn R. Pharmacokinetics of metronidazole in patients with alcoholic liver disease. Antimicrob Agents Chemother. 1987;31(11):1662-1664.[PubMed 3435113]

Leder K, Weller PF. Intestinal Entamoeba histolytica amebiasis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018a.

Leder K, Weller PF. Extraintestinal Entamoeba histolytica amebiasis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018b.

Li E, Stanley SL Jr. Protozoa. Amebiasis. Gastroenterol Clin North Am. 1996; 25(3):471-492.[PubMed 8863036 ]

Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn’s disease in adults [published correction appears in Am J Gastroenterol. 2018;113(7):1101]. Am J Gastroenterol. 2018;113(4):481-517. doi: 10.1038/ajg.2018.27.[PubMed 29610508]

Loesche WJ, Schmidt E, Smith BA, et al, “Effects of Metronidazole on Periodontal Treatment Needs,” J Periodontol, 1991, 62(4):247-57.[PubMed 2037955]

Loesche WJ, Giordano JR, Hujoel P, et al, “Metronidazole in Periodontitis: Reduced Need for Surgery,” J Clin Periodontol, 1992, 19(2):103-12.[PubMed 1602034]

Lopez-Sanromán A, Vera-Mendoza I, Domènech E, et al; Spanish GETECCU group [APPRECIA study]. Adalimumab vs azathioprine in the prevention of postoperative Crohn’s disease recurrence. A GETECCU randomised trial. J Crohns Colitis. 2017;11(11):1293-1301. doi: 10.1093/ecco-jcc/jjx051.[PubMed 28402454]

Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;18(1):1-76. doi: 10.1089/sur.2016.261.[PubMed 28085573]

McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. doi: 10.1093/cid/cix1085.[PubMed 29462280]

Metronidazole injection in sodium chloride [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; December 2017.

Mimura T, Rizzello F, Helwig U, et al. Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis. Aliment Pharmacol Ther. 2002;16(5):909-917.[PubMed 11966499]

Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017;112(7):988-1013. doi: 10.1038/ajg.2017.154.[PubMed 28631728]

Muscara MN, Pedrazzoli J Jr, Miranda EL, et al. Plasma hydroxy-metronidazole/metronidazole ratio in patients with liver disease and in healthy volunteers. Br J Clin Pharmacol.1995;40(5):477-480.[PubMed 8703652]

Nagata N, Marriott D, Harkness J, Ellis JT, Stark D. Current treatment options for Dientamoeba fragilis infections. Int J Parasitol Drugs Drug Resist. 2012;2:204-215. doi: 10.1016/j.ijpddr.2012.08.002.[PubMed 24533282]

Navaneethan U, Shen B. Pros and cons of antibiotic therapy for pouchitis. Expert Rev Gastroenterol Hepatol. 2009;3(5):547-559. doi: 10.1586/egh.09.37.[PubMed 19817675]

Nguyen GC, Loftus EV Jr, Hirano I, Falck-Ytter Y, Singh S, Sultan S; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of Crohn’s disease after surgical resection. Gastroenterology. 2017;152(1):271-275. doi: 10.1053/j.gastro.2016.10.038.[PubMed 27840074]

Ordonez-Mena JM, McCarthy ND, Fanshawe TR. Comparative efficacy of drugs for treating giardiasis: a systematic update of the literature and network meta-analysis of randomized clinical trials [published online ahead of print November 27, 2017]. J Antimicrob Chemother. doi: 10.1093/jac/dkx430.[PubMed 29186570]

Passmore CM, McElnay JC, Rainey EA, et al, “Metronidazole Excretion in Human Milk and its Effect on the Suckling Neonate,” Br J Clin Pharmacol, 1988, 26(1):45-51.[PubMed 3203060]

Pemberton JH. Acute colonic diverticulitis: medical management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 2, 2018.

Peyrin-Biroulet L, Deltenre P, Ardizzone S, et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn’s disease: a meta-analysis. Am J Gastroenterol. 2009;104(8):2089-2096. doi: 10.1038/ajg.2009.301.[PubMed 19568226]

Rabelo CC, Feres M, Gonçalves C, et al. Systemic antibiotics in the treatment of aggressive periodontitis. A systematic review and a Bayesian Network meta-analysis. J Clin Periodontol. 2015;42(7):647-657. doi: 10.1111/jcpe.12427.[PubMed 26087839]

Ross AG, Olds GR, Cripps AW, Farrar JJ, McManus DP. Enteropathogens and chronic illness in returning travelers. N Engl J Med. 2013;368(19):1817-1825.[PubMed 23656647]

Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of Crohn’s recurrence after ileal resection. Gastroenterology. 1995;108(6):1617-1621.[PubMed 7768364]

Sandhu BK, Fell JM, Beattie RM, et al. Guidelines for the management of inflammatory bowel disease in children in the United Kingdom. J Pediatr Gastroenterol Nutr. 2010;50(Suppl 1):S1-S13.[PubMed 23656647]

Schutze GE, Willoughby RE; Committee on Infectious Diseases, American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics. 2013;131(1):196-200.[PubMed 23277317]

Sexton DJ, Sampson JH. Tetanus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 10, 2018a.

Sexton DJ. Intracranial epidural abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 10, 2018b.

Shen B. Pouchitis: management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 31, 2018.

Shih G, Wallace R. First-trimester pregnancy termination: uterine aspiration. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 22, 2018.

Silva-Senem MX, Heller D, Varela VM, Torres MC, Feres-Filho EJ, Colombo AP. Clinical and microbiological effects of systemic antimicrobials combined to an anti-infective mechanical debridement for the management of aggressive periodontitis: a 12-month randomized controlled trial. J Clin Periodontol. 2013;40(3):242-251.[PubMed 23297772]

Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infections in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America [published correction appears in Clin Infect Dis. 2010;50(12):1695]. Clin Infect Dis. 2010;50(2):133-164.[PubMed 20034345]

Southwick FS. Treatment and prognosis of bacterial brain abscess. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 1, 2018.

Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America [published online ahead of print June 18, 2014]. Clin Infect Dis. 2014;59(2):147-159. doi: 10.1093/cid/ciu296.[PubMed 24947530]

St Peter SD, Little DC, Calkins CM, et al. A simple and more cost-effective antibiotic regimen for perforated appendicitis. J Pediatr Surg. 2006;41(5):1020-1024.[PubMed 16677904]

St Peter SD, Tsao K, Spilde TL, et al. Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial. J Pediatr Surg. 2008;43(6):981-985.[PubMed 18558169]

Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478-498.[PubMed 23439232]

Talley NJ and Vakil N, “Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the Management of Dyspepsia,” Am J Gastroenterol, 2005, 100(10):2324-37.[PubMed 16181387]

Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166.[PubMed 16163635]

Turner D, Levine A, Escher JC, et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55(3):340-361.[PubMed 22773060]

Upadhyaya P, Bhatnagar V, Basu N. Pharmacokinetics of intravenous metronidazole in neonates. J Pediatr Surg. 1988;23(3):263-265.[PubMed 3357144]

van der Woude CJ, Ardizzone S, Bengtson MB, et al; European Crohn’s and Colitis Organization. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015;9(2):107-124.[PubMed 25602023 ]

van Schalkwyk J, Yudin MH, Infectious Disease Committee. Vulvovaginitis: screening for and management of trichomoniasis, vulvovaginal candidiasis, and bacterial vaginosis. J Obstet Gynaecol Can. 2015;37(3):266-274.[PubMed 26001874]

Varela VM, Heller D, Silva-Senem MX, et al, “Systemic Antimicrobials Adjunctive to a Repeated Mechanical and Antiseptic Therapy for Aggressive Periodontitis: A 6-Month Randomized Controlled Trial,” J Periodontol, 2011, 82(8):1121-30.[PubMed 21235333]

Visser AA and Hundt HK, “The Pharmacokinetics of a Single Intravenous Dose of Metronidazole in Pregnant Patients,” J Antimicrob Chemother, 1984, 13(3):279-83.[PubMed 6725177 ]

Wall GC, Shirmer LL, Anliker LE, Tigges AE. Pharmacotherapy for acute pouchitis. Ann Pharmacother. 2011;45(9):1127-1137.[PubMed 21775695]

Wang X, Nanovskaya TN, Zhan Y, et al, “Pharmacokinetics of Metronidazole in Pregnant Patients With Bacterial Vaginosis,” J Matern Fetal Neonatal Med, 2011, 24(3):444-8.[PubMed 20608802]

Wang B, Wang YH, Lv ZF, et al. Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection: a systematic review and meta-analysis. Helicobacter. 2015;20(2):79-88. doi: 10.1111/hel.12180.[PubMed 25381839]

Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int. 2012;32(Suppl 2):S32-S86.[PubMed 22851742]

Weller PF, Leder K. Balantidium coli infection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2018.

Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.[PubMed 26042815]

World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the Eleventh WHO Model List of Essential Drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en/[PubMed 23215911]

Yardeni D, Kawar B, Siplovich L, et al. Single daily dosing of ceftriaxone and metronidazole is as safe and effective as ampicillin, gentamicin and metronidazole for non-operative management of complicated appendicitis in children. Pediat Therapeut. 2013;3:5.

Yudin MH, Money DM. No. 211-Screening and management of bacterial vaginosis in pregnancy. J Obstet Gynaecol Can. 2017;39(8):e184-e191.[PubMed 28729110]

Brand Names: International

Agometrol (TZ); Amevan (EC); Amgyl (LK); Amotrex (BD); Amrizole (BH, EG, QA); Anaemetro (JP); Anaerobex (AT); Anaerobyl (ZW); Anazol (AE, QA); Anerobizol (PH); Antizoal (PH); Ao Ke An (CN); Arilin (DE); Asiazole (TH); Axagyl (PH); Biatron (ID); Camezol (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); Clont (DE); Clovizole (PH); Dazolin (ID); Deflamon (IT); Dequazol Oral (PE); Dirozyl (BD); Dumozol (AE, CY, JO, KW, SA); Efloran (CZ, UA); Elyzol (FI); Endazole (PH); Entazole (EG); Entizol (CZ); Farcozole (EG); Farnat (ID); Fentiazol (PY); Fladex (ID); Flagesol (UY); Flagizole (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Flagyl (AR, AU, BB, BE, BG, BH, BR, CH, CL, CO, CU, CY, EC, EG, ES, FR, GB, GR, HK, ID, IE, IL, IN, IS, JO, KR, KW, LB, LK, LU, MT, NL, NO, NZ, PE, PH, PK, PT, QA, RO, RU, SA, SG, SI, TH, TR, TW, UA, VE, VN, ZW); Flasinyl (KR); Flazol (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Flazole (LV); Fogyl (MY); Frotin (HK, MY, TW); Fu Shu Da (CN); Gravagin (UA); Gynoplix (HK); Helmizol (BR); Klont (MT); Medazol (HR); Metason (LK); Metazol (ZA); Metgyl (MY); Metris (ZW); Metrogyl (AU, ET); Metrolag (AE, BF, BJ, CH, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TW, TZ, UG, YE, ZM, ZW); Metrolex (TH); Metronidazole IV (AU, NZ); Metronide (AU); Metrorex (ET); Metrozin (CO); Molazol (ID); Nalox (AR); Narobic (ZA); Negazole (ET, QA); Nidazole (AE, BH, JO, QA, SA); Nirmet (TH); Normet (ET); Norzol (MT); Novazole (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); Patryl (PH); Progyl (ID); Protozol (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); Protozole (PH); Qualigyl (HK); Qugyl (BD); Rodazid (PH); Ronazol (ID); Sharizole (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Sicabact (ET); Supplin (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Trichex (AT); Trizele (KR); Trogiar (ID); Trogyl (ID); Unigo (HK, TH); Vadazol (ID); Vertisal (CR, DO, GT, HN, NI, PA, SV); Zidoval (AU); Zol (PH)

Metronidazole (Systemic) (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

(met roe NYE da zole)

Brand Names: US

Flagyl

Brand Names: Canada

Flagyl

Warning
  • Metronidazole has been shown to cause cancer in mice and rats with long-term use. Talk with the doctor.
  • The doctor has given you this drug for a certain health problem. Do not use this drug for other health problems.
What is this drug used for?
  • It is used to treat infections.
  • It is used to prevent infections during bowel surgery.
  • 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 metronidazole 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 taken disulfiram within the past 2 weeks.
  • If you are less than 12 weeks pregnant. This drug is not for use in certain patients who are less than 12 weeks pregnant.
  • If you are breast-feeding. Do not breast-feed for 24 hours after getting this drug.
  • 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.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • 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.
  • Avoid alcohol and products that have alcohol or propylene glycol in them while taking this drug and for at least 72 hours after your last dose. Drinking alcohol or taking products that have alcohol or propylene glycol in them, like some cough syrups, may cause cramps, upset stomach, headaches, and flushing.
  • Do not use longer than you have been told. A second infection may happen.
  • Nervous system problems have happened with this drug. Some people who took this drug for a long time have had nerve problems that lasted for a long time. Call your doctor right away if you have a burning, numbness, or tingling feeling that is not normal; change in balance or eyesight; dizziness or passing out; headache; not able to sleep; seizures; or trouble speaking. Call your doctor right away if you feel confused, depressed, irritable, tired, or weak.
  • 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.
  • Infusion:
  • If you are on a low-sodium or sodium-free diet, talk with your doctor. Some of these products have sodium.
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 a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Not able to control eye movements.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Shortness of breath.
  • Any unexplained bruising or bleeding.
  • Swelling in the arms or legs.
  • Redness or white patches in mouth or throat.
  • Vaginal itching or discharge.
  • This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call your doctor right away if you have a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother your eyes, feeling sleepy, or feeling confused.
  • Low white blood cell counts have happened with this drug. This may lead to a higher chance of getting an infection. Call your doctor right away if you have signs of infection like fever, chills, or sore throat.
  • Some people with Cockayne syndrome have had liver problems when taking this drug. Sometimes, this has been deadly. If you have Cockayne syndrome and are taking this drug, call your doctor right away if you have 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.
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 products:
  • Upset stomach or throwing up.
  • Diarrhea.
  • Constipation.
  • Not hungry.
  • Stomach cramps.
  • Stomach pain.
  • Metallic taste.
  • Feeling sleepy.
  • Muscle or joint pain.
  • Muscle spasm.
  • Lowered interest in sex.
  • Infusion:
  • Irritation where this drug 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:
  • 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.
  • Infusion:
  • 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.
  • Infusion:
  • 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.
  • Infusion:
  • 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.
Metronidazole (Systemic) (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

(met roe NYE da zole)

Brand Names: US

Flagyl

Brand Names: Canada

Flagyl

Warning
  • Metronidazole has been shown to cause cancer in mice and rats with long-term use. Talk with the doctor.
  • The doctor has given you this drug for a certain health problem. Do not use this drug for other health problems.
What is this drug used for?
  • It is used to treat infections.
  • It is used to prevent infections during bowel surgery.
  • 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 taken disulfiram within the past 2 weeks.
  • If your child is less than 12 weeks pregnant:
  • This drug is not for use in certain patients who are less than 12 weeks pregnant.
  • If your child is breast-feeding a baby:
  • Be sure your child does not breast-feed a baby for 24 hours after getting this drug.
  • 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?
  • All products:
  • 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 blood work checked as you have been told by the doctor. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • 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.
  • Alcohol interacts with this drug. Be sure your child does not drink alcohol. Be sure your child does not take products that have alcohol or propylene glycol in them while taking this drug and for at least 72 hours after the last dose. Drinking alcohol or taking products that have alcohol or propylene glycol in them, like some cough syrups, may cause cramps, upset stomach, headaches, and flushing.
  • Do not give to your child longer than you have been told. A second infection may happen.
  • 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.
  • Infusion:
  • If your child is on a low-sodium or sodium-free diet, talk with the doctor. Some of these products have sodium.
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 a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Not able to control eye movements.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Shortness of breath.
  • Any unexplained bruising or bleeding.
  • Swelling in the arms or legs.
  • Redness or white patches in mouth or throat.
  • Vaginal itching or discharge.
  • Nervous system problems have happened with this drug. Some people who took this drug for a long time have had nerve problems that lasted for a long time. Call your child’s doctor right away if your child has a burning, numbness, or tingling feeling that is not normal; change in balance or eyesight; dizziness or passing out; headache; not able to sleep; seizures; or trouble speaking. Call your child’s doctor right away if your child feels confused, depressed, irritable, tired, or weak.
  • This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call the doctor right away if your child has a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother the eyes, feeling sleepy, or feeling confused.
  • Low white blood cell counts have happened with this drug. This may lead to a higher chance of getting an infection. Call your child’s doctor right away if your child has signs of infection like fever, chills, or sore throat.
  • Some people with Cockayne syndrome have had liver problems when taking this drug. Sometimes, this has been deadly. If your child has Cockayne syndrome and is taking this drug, call your child’s doctor right away if your child has 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.
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 products:
  • Upset stomach or throwing up.
  • Diarrhea.
  • Constipation.
  • Not hungry.
  • Stomach cramps.
  • Stomach pain.
  • Metallic taste.
  • Feeling sleepy.
  • Muscle or joint pain.
  • Muscle spasm.
  • If your child is or may be sexually active:
  • Lowered interest in sex.
  • Infusion:
  • Irritation where this drug 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:
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • To gain the most benefit, do not miss giving your child doses.
  • 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.
  • Infusion:
  • 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.
  • Infusion:
  • 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.
  • Infusion:
  • 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.