metronidazole (Rx)

Brand and Other Names:Flagyl, Flagyl ER, more...Flagyl IV RTU, Likmez

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 375mg

tablet

  • 250mg
  • 500mg

tablet, extended-release

  • 750mg

oral suspension

  • 500mg/5mL (Likmez)

infusion solution

  • 500mg/100mL

Anaerobic Bacterial Infections

Loading dose: 15 mg/kg IV; not to exceed 4 g/day  

Maintenance dose: 7.5 mg/kg PO/IV (over 1 h) q6hr x 7-10 days (or 2-3 weeks if severe)

Oral suspension

  • 7.5 mg/kg PO q8hr for 7-10 days; not exceed a 4 g/24 hr
  • Infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment

Sexually Transmitted Disease

Prevention following sexual assault

2 g PO as a single dose; 3-drug regimen that also includes ceftriaxone or cefixime, PLUS azithromycin or doxycycline (CDC STD guidelines, 2010)

Bacterial Vaginosis

Nonpregnant women

  • 500 mg PO BID x 7 days, OR
  • 2 g PO qDay single dose, OR
  • Extended-release: 750 mg PO qDay x 7 days

Pregnant women

  • 500 mg PO BID x 7 days, OR
  • 250 mg PO TID x 7 days

Colorectal Surgical Infection

Prophylaxis; start after mechanical bowel preparation the afternoon and evening before surgery

1 g PO q6-8hr for 3 doses

15 mg/kg IV over 30-60 min; complete approximately 1 hr before surgery; may administer 7.5 mg/kg IV over 30-60 min at 6 and 12 hr after initial dose for maintenance; discontinue within 12 hr after surgery

Trichomoniasis

250 mg PO q8hr for 7 days

2 g PO qDay single dose; alternatively, 1g PO q12hr for 2 doses

Individualize dosage regimen

  • Single-dose treatment may help improve compliance, especially if administered under supervision, in those patients who may be nonadherent to a seven-day regimen
  • Seven-day treatment may minimize reinfection by protecting patient long enough for sexual contacts to obtain appropriate treatment; some data suggest cure rates may be higher after a seven-day course of treatment than after a one-day treatment regimen;
  • If a repeat course of therapy is required, a 4- to 6-weeks need to elapse between courses and reconfirmed presence of the trichomonad; monitor total and differential leukocyte counts before and after re-treatment

Amebiasis

Acute intestinal amebiasis (acute amebic dysentery): 750 mg PO TID 5-10 days

Amebic liver abscess: 500-750 mg PO TID for 5-10 days

Giardiasis (Off-label)

500 mg PO q12hr for 5-7 days

Gardnerella Infection

Immediate release: 500 mg PO q12hr

Extended-release: 750 mg PO qDay for 7 days; take on empty stomach

Helicobacter Pylori Infection (Off-label)

250-500 mg PO QID in combination with tetracycline (500 mg) and bismuth subsalicylate (525 mg) x 14 days

Nongonococcal Urethritis (Off-label)

2 g PO qDay single dose with erythromycin (500 mg QID) or erythromycin ethylsuccinate (800 mg QID) x 7 days

Pelvic Inflammatory Disease (Off-label)

500 mg PO q12hr for 14 days in conjunction with ofloxacin or levofloxacin

Dosage Modifications

Renal impairment

  • Mild-to-moderate: Dose adjustment not considered necessary as elimination half-life not significantly altered
  • Severe or end-stage renal disease: Metronidazole and metronidazole metabolites may accumulate significantly because of reduced urinary excretion; monitor patients not undergoing hemodialysis
  • Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation; supplementation may be necessary
  • Peritoneal dialysis: Monitor for signs of toxicity due to potential accumulation of metronidazole metabolites

Hepatic impairment

  • Mild-to- moderate (Child-Pugh A or B): No dosage adjustment necessary; monitor
  • Severe (Child-Pugh C): Reduce dose of by 50%

Dosing Considerations

Hepatic failure

  • Mild to moderate hapatic impairment (Child-Pugh A or B): No dosage adjustment needed but patients should be monitored for metronidazole associated adverse events
  • Severe hepatic impairment: Reduce dose of by 50%

Renal failure

  • Mild to moderate renal impairment: Dose adjustment not considered necessary as elimination half-life not significantly altered
  • Severe renal impairment or end stage of renal disease: Metronidazole and metronidazole metabolites may accumulate significantly because of reduced urinary excretion; monitor in severe renal impairment or end stage of renal disease, not undergoing hemodialysis
  • Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation; supplementation may be necessary
  • Peritoneal dialysis: Monitor for signs of toxicity due to potential accumulation of metronidazole metabolites

Dosing Considerations

To reduce developing drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, use metronidazole only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria

When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy

In the absence of such data, local epidemiology and susceptibility patterns may help in selecting an empiric therapy

Pouchitis (Orphan)

Orphan indication sponsor

  • Formac Pharmaceuticals, NV; Gaston Geenslaan 1; Belgium

Crohn Disease (Orphan)

Topical treatment of active perianal Crohn disease

Orphan indication sponsor

  • Braintree Laboratories, Inc; 60 Columbian Street West; PO Box 850929; Braintree, MA 02185-0929

Perioral Dermatitis (Orphan)

Orphan indication sponsor

  • Galderma Laboratories, Inc; P.O. Box 331329; Fort Worth, TX 76163

Dosage Forms & Strengths

capsule

  • 375mg

tablet

  • 250mg
  • 500mg

tablet, extended-release

  • 750mg

oral suspension

  • 500mg/5mL (Likmez)

infusion solution

  • 500mg/100mL

Neonatal (<28 Days) Anaerobic Infection

<1.2 kg

  • 7.5 mg/kg IV/PO q48hr  

<7 days

  • 1.2-2 kg: 7.5 mg/kg IV/PO qDay
  • >2 kg: 15 mg/kg/day IV/PO divided q12hr

>7 days

  • 1.2-2 kg: 15 mg/kg/day IV/PO divided q12hr
  • >2 kg: 30 mg/kg/day IV/PO divided q12hr

Infants and Children

  • 30 mg/kg/day PO/IV divided q6hr; not to exceed 4 g/day

Clostridium Difficile Colitis

30 mg/kg/day IV/PO divided q6hr IV/PO for 7-10 days (American Academy of Pediatrics)  

Amebiasis

35-50 mg/kg/day PO divided q8hr (not to exceed 2,250 mg/24 hours [maximum dose 750 mg/dose]) for 10 days  

Giardiasis

15 mg/kg/day IV/PO divided q8hr for 5 days  

Trichomoniasis

< 45 kg body weight: 15 mg/kg/day IV/PO divided q8hr for 7 days; not to exceed 2 g/day  

Helicobacter Pylori-Associated Peptic Ulcer Disease (Off-label)

With amoxicillin and bismuth subsalicylate: 15-20 mg/kg/day PO divided q12hr for 4 weeks  

Dosage Modifications

Renal impairment

  • Mild-to-moderate: Dose adjustment not considered necessary as elimination half-life not significantly altered
  • Severe or end-stage renal disease: Metronidazole and metronidazole metabolites may accumulate significantly because of reduced urinary excretion; monitor patients not undergoing hemodialysis
  • Hemodialysis removes significant amounts of metronidazole and its metabolites from systemic circulation; supplementation may be necessary
  • Peritoneal dialysis: Monitor for signs of toxicity due to potential accumulation of metronidazole metabolites

Hepatic impairment

  • Mild-to- moderate (Child-Pugh A or B): No dosage adjustment necessary; monitor
  • Severe (Child-Pugh C): Reduce dose of by 50%

Dosing Considerations

To reduce developing drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, use metronidazole only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria

When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy

In the absence of such data, local epidemiology and susceptibility patterns may help in selecting an empiric therapy

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Interactions

Interaction Checker

and metronidazole

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            Contraindicated (4)

            • dronabinol

              metronidazole increases toxicity of dronabinol by aldehyde dehydrogenase inhibition. Contraindicated. Dronabinol oral solution (Syndros) contains 50% (w/w) dehydrated alcohol 5.5% (w/w) propylene glycol, which can produce disulfiramlike reactions if coadministered with metronidazole. Discontinue metronidazole at least 14 days before starting dronabinol solution and do not administer metronidazole within 7 days of completing treatment with dronabinol solution.

            • flibanserin

              metronidazole will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

            • lomitapide

              metronidazole increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • lonafarnib

              metronidazole will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            Serious - Use Alternative (52)

            • avapritinib

              metronidazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • axitinib

              metronidazole increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with moderate CYP3A4 inhibitors, monitor closely and reduce dose if necessary .

            • BCG vaccine live

              metronidazole decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

            • bosutinib

              metronidazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cholera vaccine

              metronidazole, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

            • cobimetinib

              metronidazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

            • dihydroergotamine

              metronidazole will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dihydroergotamine intranasal

              metronidazole will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • disulfiram

              disulfiram increases toxicity of metronidazole by decreasing metabolism. Contraindicated. Enhanced CNS & cardiac toxicity.

            • dronedarone

              metronidazole will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • elacestrant

              metronidazole will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eliglustat

              metronidazole increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

            • entrectinib

              metronidazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • ergotamine

              metronidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin base

              metronidazole will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              metronidazole will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              metronidazole will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              metronidazole will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • everolimus

              metronidazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fentanyl

              metronidazole will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl intranasal

              metronidazole will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transdermal

              metronidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transmucosal

              metronidazole will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • infigratinib

              metronidazole will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivabradine

              metronidazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.

            • lemborexant

              metronidazole will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lovastatin

              metronidazole will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lurbinectedin

              metronidazole will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mebendazole

              mebendazole increases toxicity of metronidazole by Other (see comment). Avoid or Use Alternate Drug. Comment: May increase the risk for toxic epidermal necrolysis or Stevens-Johnson syndrome.

            • midazolam intranasal

              metronidazole will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • mobocertinib

              metronidazole will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • naloxegol

              metronidazole will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • neratinib

              metronidazole will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

            • olaparib

              metronidazole will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • omaveloxolone

              metronidazole will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

            • pacritinib

              metronidazole will increase the level or effect of pacritinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.

            • pemigatinib

              metronidazole will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pexidartinib

              metronidazole will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • pimozide

              metronidazole increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.

            • propylene glycol

              metronidazole, propylene glycol. Mechanism: decreasing metabolism. Contraindicated. Disulfiram like reaction.

            • ranolazine

              metronidazole will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • repotrectinib

              metronidazole will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.

            • selinexor

              selinexor, metronidazole. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • selumetinib

              metronidazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • silodosin

              metronidazole will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • simvastatin

              metronidazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • siponimod

              metronidazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sirolimus

              metronidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tazemetostat

              metronidazole will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • tolvaptan

              metronidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • typhoid vaccine live

              metronidazole decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

            • venetoclax

              metronidazole will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a moderate CYP3A inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

            Monitor Closely (139)

            • acalabrutinib

              metronidazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • almotriptan

              metronidazole will increase the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              metronidazole will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amifampridine

              metronidazole increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amiodarone

              metronidazole will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aprepitant

              metronidazole will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aripiprazole

              metronidazole will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              metronidazole will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atogepant

              metronidazole will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atorvastatin

              metronidazole will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • avanafil

              metronidazole will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors

            • bazedoxifene/conjugated estrogens

              metronidazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bortezomib

              metronidazole will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexpiprazole

              metronidazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

            • budesonide

              metronidazole will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine subdermal implant

              metronidazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              metronidazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

              metronidazole will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cabozantinib

              metronidazole will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cannabidiol

              metronidazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • capivasertib

              metronidazole will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.

            • carbamazepine

              metronidazole will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carvedilol

              metronidazole will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • cholestyramine

              cholestyramine decreases levels of metronidazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • cilostazol

              metronidazole will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinacalcet

              metronidazole will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clopidogrel

              metronidazole will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Inhibition of CYP3A4 will reduce clopidogrel bioactivation

            • clozapine

              metronidazole will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conivaptan

              metronidazole will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens

              metronidazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              metronidazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

              metronidazole will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyclosporine

              metronidazole will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • daridorexant

              metronidazole will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

            • darifenacin

              metronidazole will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              metronidazole will increase the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              metronidazole will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              metronidazole will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

            • dexamethasone

              metronidazole will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam

              metronidazole will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam intranasal

              metronidazole will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • digoxin

              metronidazole will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.

            • eletriptan

              metronidazole will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erlotinib

              metronidazole will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estradiol

              metronidazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens conjugated synthetic

              metronidazole will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

              metronidazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethanol

              metronidazole, ethanol. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.

            • ethinylestradiol

              metronidazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ethotoin

              metronidazole will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • etonogestrel

              metronidazole will increase the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etravirine

              metronidazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              metronidazole will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • felodipine

              metronidazole will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fesoterodine

              metronidazole will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • finerenone

              metronidazole will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fludrocortisone

              metronidazole will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluorouracil

              metronidazole increases toxicity of fluorouracil by decreasing elimination. Use Caution/Monitor.

            • fosamprenavir

              metronidazole will increase the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosaprepitant

              metronidazole will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              metronidazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • gepirone

              metronidazole will increase the level or effect of gepirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce gepirone dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor.

            • guanfacine

              metronidazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • hydrocortisone

              metronidazole will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydroxyprogesterone caproate (DSC)

              metronidazole will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibrutinib

              metronidazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

            • ifosfamide

              metronidazole decreases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

              metronidazole will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indinavir

              metronidazole will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isavuconazonium sulfate

              metronidazole will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              metronidazole will increase the level or effect of isoniazid by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

            • ivacaftor

              metronidazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivosidenib

              metronidazole will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

            • ixabepilone

              metronidazole will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lapatinib

              metronidazole will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lefamulin

              metronidazole will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • levamlodipine

              metronidazole will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              metronidazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • lopinavir

              metronidazole will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loratadine

              metronidazole will increase the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • losartan

              metronidazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

            • lumateperone

              metronidazole will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

            • lumefantrine

              metronidazole will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • maraviroc

              metronidazole will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mavacamten

              metronidazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • mefloquine

              metronidazole will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mestranol

              metronidazole will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methadone

              metronidazole will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methylprednisolone

              metronidazole will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • midazolam

              metronidazole will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • naldemedine

              metronidazole increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

            • nateglinide

              metronidazole will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • nelfinavir

              metronidazole will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              metronidazole will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

              metronidazole will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nisoldipine

              metronidazole will increase the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norgestrel

              metronidazole will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects

            • oliceridine

              metronidazole will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • palbociclib

              metronidazole will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • palovarotene

              metronidazole will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of palovarotene, a CYP3A substrate, with moderate CYP3A inhibitors. If unavoidable, reduce palovarotene dose by 50%.

            • parecoxib

              metronidazole will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • pazopanib

              metronidazole will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

            • phenytoin

              metronidazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • prednisone

              metronidazole will increase the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quetiapine

              metronidazole will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinidine

              metronidazole will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • repaglinide

              metronidazole will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rimegepant

              metronidazole will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • ritonavir

              metronidazole will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ruxolitinib

              metronidazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ruxolitinib topical

              metronidazole will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

              metronidazole will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              metronidazole decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.

            • solifenacin

              metronidazole will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sonidegib

              metronidazole will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sparsentan

              metronidazole will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

            • sufentanil SL

              metronidazole will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sulfamethoxazole

              metronidazole, sulfamethoxazole. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.

            • sunitinib

              metronidazole will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • suvorexant

              metronidazole will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

            • tacrolimus

              metronidazole will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tadalafil

              metronidazole will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tamoxifen

              metronidazole, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

            • tamsulosin

              metronidazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • temsirolimus

              metronidazole will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tezacaftor

              metronidazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • theophylline

              metronidazole will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tinidazole

              metronidazole will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tipranavir

              metronidazole will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tofacitinib

              metronidazole increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors.

            • tolterodine

              metronidazole will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trabectedin

              metronidazole will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trazodone

              metronidazole will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              metronidazole will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triazolam

              metronidazole will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vardenafil

              metronidazole will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

            • verapamil

              metronidazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voclosporin

              metronidazole will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

            • warfarin

              metronidazole increases levels of warfarin by unspecified interaction mechanism. Use Caution/Monitor. Metronidazole may potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. .

            • zanubrutinib

              metronidazole will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            Minor (76)

            • acetaminophen

              metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • acetaminophen IV

              metronidazole will increase the level or effect of acetaminophen IV by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • acetaminophen rectal

              metronidazole will increase the level or effect of acetaminophen rectal by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • alfentanil

              metronidazole will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alfuzosin

              metronidazole will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alosetron

              metronidazole will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              metronidazole will increase the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amitriptyline

              metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • armodafinil

              metronidazole will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atazanavir

              metronidazole will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • balsalazide

              metronidazole will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • biotin

              metronidazole will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • bosentan

              metronidazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              metronidazole will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • celecoxib

              metronidazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • cevimeline

              metronidazole will increase the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • clarithromycin

              metronidazole will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • clomipramine

              metronidazole will increase the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dapsone

              metronidazole will increase the level or effect of dapsone by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

              metronidazole will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • diclofenac

              metronidazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • didanosine

              didanosine, metronidazole. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Enhanced risk of peripheral neuropathy.

            • disopyramide

              metronidazole will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • docetaxel

              metronidazole will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              metronidazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dutasteride

              metronidazole will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • efavirenz

              metronidazole will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eplerenone

              metronidazole will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • estradiol vaginal

              metronidazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ethanol

              metronidazole will increase the level or effect of ethanol by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • eucalyptus

              metronidazole will increase the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • finasteride

              metronidazole will increase the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • flurbiprofen

              metronidazole will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • fluvastatin

              metronidazole will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • galantamine

              metronidazole will increase the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ibuprofen

              metronidazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • ibuprofen IV

              metronidazole will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • imatinib

              metronidazole will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imipramine

              metronidazole will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • irinotecan

              metronidazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • irinotecan liposomal

              metronidazole will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • isradipine

              metronidazole will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • itraconazole

              metronidazole will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketoconazole

              metronidazole will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levoketoconazole

              metronidazole will increase the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lithium

              metronidazole increases levels of lithium by decreasing metabolism. Minor/Significance Unknown.

            • meloxicam

              metronidazole will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • montelukast

              metronidazole will increase the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              metronidazole will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nimodipine

              metronidazole will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              metronidazole will increase the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitroglycerin IV

              nitroglycerin IV, metronidazole. Mechanism: decreasing metabolism. Minor/Significance Unknown. Disulfiram like reaction.

            • oxybutynin

              metronidazole will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              metronidazole will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              metronidazole will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pantothenic acid

              metronidazole will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • parecoxib

              metronidazole will increase the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pimozide

              metronidazole will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

              metronidazole will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • piroxicam

              metronidazole will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • propafenone

              metronidazole will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pyridoxine

              metronidazole will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • pyridoxine (Antidote)

              metronidazole will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • quinine

              metronidazole will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramelteon

              metronidazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              metronidazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • saxagliptin

              metronidazole will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sufentanil

              metronidazole will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfamethoxazole

              metronidazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • thiamine

              metronidazole will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • tolbutamide

              metronidazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • vinblastine

              metronidazole will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vincristine

              metronidazole will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vincristine liposomal

              metronidazole will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vinorelbine

              metronidazole will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • voriconazole

              metronidazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • zaleplon

              metronidazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ziprasidone

              metronidazole will increase the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zolpidem

              metronidazole will increase the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zonisamide

              metronidazole will increase the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            Appetite loss

            Candidiasis

            Diarrhea

            Dizziness

            Headache

            Nausea

            Vomiting

            Ataxia

            Dark urine

            Disulfiram-type reaction with ethanol

            Furry tongue

            Hypersensitivity

            Neutropenia

            Metallic taste

            Neuropathy

            Pancreatitis

            Seizures

            Thrombophlebitis

            Xerostomia

            Encephalopathy

            Aseptic meningitis

            Optic neuropathy

            Stevens-Johnson syndrome

            Toxic epidermal necrolysis

            Decreased libido

            Postmarketing Reports

            Dyspareunia, proctitis, fleeting joint pains that may resemble serum sickness, Crohn’s disease, hiccup, psychosis

            Gastrointestinal: Anorexia,

            epigastric distress, abdominal cramping

            Mouth: Glossitis, stomatitis

            Hematopoietic: Reversible neutropenia (leukopenia); thrombocytopenia, eosinophilia

            Hepatobiliary disorders: Hepatotoxicity and liver failure especially in patients with Cockayne syndrome, jaundice

            Cardiovascular: QT prolongation

            Skin and subcutaneous disorders: Eosinophilia and systemic symptoms (DRESS), erythematous rash, bullae, pruritus, swelling face, urticaria, hyperhidrosis, acute generalized exanthematous pustulosis (AGEP), flushing, nasal congestion, dryness of mouth, vagina, or vulva, fever

            Central nervous system: Dizziness, vertigo, incoordination, ataxia, confusion, psychosis, dysarthria, irritability, depression, weakness, headache, and insomnia

            Severe irreversible hepatotoxicity/acute liver failure (patients with Cockayne syndrome)

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            Warnings

            Black Box Warnings

            Potenial for carcinogenicity

            • Metronidazole has been shown to be carcinogenic in mice and rats
            • Avoid unnecessary use
            • Reserve for use in trichomoniasis and anaerobic bacterial infection

            Contraindications

            Hypersensitivity to metronidazole or other nitroimidazoles (although cautious desensitization has been applied)

            Pregnancy, 1st trimester in patients with trichomoniasis

            Use of disulfiram within past 2 weeks; use of alcohol during therapy or within 3 days of discontinuing therapy

            Consumption of alcohol or products containing propylene glycol within least three days of receiving metronidazole

            Patients with Cockayne syndrome

            Cautions

            Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes reported after initiation of metronidazole, another nitroimidazole drug, structurally related to benznidazole in patients with Cockayne syndrome

            Seizures and aseptic meningitis reported with increase in dose and chronic therapy

            Cases of encephalopathy and peripheral neuropathy (including optic neuropathy) reported with metronidazole

            Encephalopathy reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria; CNS lesions seen on MRI described in reports of encephalopathy; CNS symptoms are generally reversible within days to weeks upon discontinuation of therapy; lesions seen on MRI have also been described as reversible

            Peripheral neuropathy, mainly of sensory type reported and characterized by numbness or paresthesia of an extremity

            Prescribing metronidazole tablets in absence of a proven or strongly suspected bacterial or parasitic infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria and parasites

            Superinfection may occur with prolonged use

            Severe hepatic impairment; administer lower doses with caution

            Use with caution; potential accumulation in end stage renal disease; supplemental doses may be needed in patients receiving hemodialysis

            Use with caution in history of heart failure, hepatic failure, H. pylori infection, renal impairment

            Use with care in patients with evidence of or history of blood dyscrasia; agranulocytosis, leukopenia and neutropenia have been associated with metronidazole administration; monitor complete blood count; monitor complete blood count (CBC) for leukopenia before, during, and after prolonged repeated therapy

            Avoid alcohol while taking medication and for at least three days after discontinuation

            Antiandrogen: May cause gynecomastia

            Known or previously unrecognized candidiasis may present more prominent symptoms during therapy and requires treatment with a candicidal agent

            Metronidazole injection, USP contains 790 mg of sodium per 100 mL; use care when administering injection to patients receiving a controlled sodium diet or corticosteroids or to patients predisposed to edema

            Severe neurological disturbances, including encephalopathy, cerebellar symptoms, convulsive seizures, and aseptic meningitis, reported in patients treated with metronidazole; advise patients to report neurologic symptoms that occur during metronidazole administration; discontinue metronidazole treatment if any abnormal neurologic symptoms occur such as ataxia, dizziness, confusion or any other CNS adverse reaction

            Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome reported with products containing metronidazole for systemic use; in this population, metronidazole should therefore be used after careful benefit-risk assessment and only if no alternative treatment available; obtain liver function tests prior to start of therapy, within first 2-3 days after initiation of therapy, frequently during therapy and after end of treatment; discontinue metronidazole if elevation of liver function occurs, and monitor liver function tests until baseline values are reached; advise patients with Cockayne syndrome to stop taking metronidazole immediately if they experience any symptoms of potential liver injury, such as abdominal pain, nausea, change in stool color or jaundice, and to contact their healthcare provider

            When metronidazole tablets are prescribed to treat a bacterial infection, patients should be told that the medication should be taken exactly as directed; skipping doses or not completing full course of therapy may decrease effectiveness of immediate treatment and increase likelihood that bacteria will develop resistance and will not be treatable by metronidazole tablets in the future

            Drug interaction overview

            • Metronidazole reported to potentiate anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages; prothrombin time and international normalized ratio (INR) should be carefully monitored and anticoagulant dose adjusted accordingly; monitor patients for signs and symptoms of bleeding
            • Metronidazole reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis, and hepatic veno-occlusive disease; metronidazole should not be administered concomitantly with busulfan unless benefit outweighs risk
            • Simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity
            • Simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate elimination of metronidazole and therefore decrease its efficacy
            • Concomitant use of metronidazole and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin, and quinidine) may increase respective CYP3A4-substrate plasma levels; monitoring of plasma concentrations of CYP3A4 substrates may be necessary
            • Metronidazole decreases clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity
            • Metronidazole may potentiate effects of vecuronium
            • QT prolongation reported, particularly when metronidazole administered with drugs with potential for prolonging QT interval; flattening of T-wave may be seen in electrocardiographic tracings
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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies of in pregnant females

            Many studies included first trimester exposures; one study showed increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed

            Metronidazole crosses placental barrier and its effects on human fetal organogenesis are not known

            Animal data

            • Reproduction studies have been performed in rats, rabbits and mice at doses similar to maximum recommended daily dose based on body surface area comparisons; there was no evidence of harm to fetus due to metronidazole
            • Carefully consider potential risks and benefits for each specific patient before prescribing therapy

            Lactation

            Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels; there are no data on effects of metronidazole on milk production

            Because of potential for carcinogenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother

            The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from this drug or from underlying maternal condition

            Alternatively, a nursing mother may choose to pump and discard human milk for duration of metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Inhibits nucleic acid synthesis by disrupting DNA and causing strand breakage; amebicidal, bactericidal, trichomonacidal

            Absorption

            Peak plasma concentration

            • IV (steady-state): 25 mcg/mL
            • Capsule: 20.4-21.4 mcg/mL (fasted)
            • Oral solution and tablets: 6 mcg/mL (250-mg dose); 12 mcg/mL (500-mg dose); 40 mcg/mL (2,000-mg dose)

            Trough levels

            • IV: 18 mcg/mL

            Peak plasma time

            • Capsule: 1.4-1.6 hr (fasted)
            • Tablet: 1-2 hr
            • Oral solution: 0.25-6 hr

            AUC

            • Capsule: 218-223 mcg⋅hr/mL (fasted); 99 mcg⋅hr/mL (fed)

            Distribution

            Protein bound: <20%

            Metabolism

            Side-chain oxidation resulting in 2 metabolites (1-(ßhydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-ylacetic acid)

            Glucuronide conjugation

            Elimination

            Clearance: 10 hr (PO)

            Half-life

            • Capsule or tablet: 8 hr
            • Oral solution: 10 hr

            Excretion

            • PO or IV: 60-80% (urine); 6-15% (feces)
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            Administration

            IV Incompatibilities

            Some drugs may be incompatible with reconstituted solution from powder (which contains metronidazole HCl) but compatible with RTU IV solution (which contains metronidazole), and vice versa

            Additive: Aztreonam, cefepime(?), ciprofloxacin (may be compatible with RTU solution), dopamine, meropenem

            Y-site: Amphotericin B cholesteryl sulfate, aztreonam, filgrastim, meropenem, warfarin

            IV Preparation

            Reconstitute powder with 4.4 mL sterile water for injection, bacteriostatic water for injection, NS, or bacteriostatic NS to a final concentration of 100 mg/mL (pH 0.5-2)

            Further dilute in glass or plastic container to no more than 8 mg/mL with NS, D5W, or LR

            Neutralize with approximately 5 mEq NaHCO3 per 500 mg metronidazole; final pH 6-7

            No dilution or buffering necessary for ready-to-use IV solution

            IV Administration

            Infusion only

            Avoid contact between drug and aluminum in infusion set (less critical for RTU infusion solution containing metronidazole rather than metronidazole HCl)

            Oral Administration

            Oral solution

            • Shake the bottle well before administering
            • Use a calibrated oral dosing device to correctly measure the prescribed dose of medication; do not use household teaspoons or tablespoons to measure doses.
            • Calibrated oral dosing devices may be obtained from the pharmacy

            Storage

            IV

            • Store at 15-30°C
            • Protect from light

            Capsules

            • Store between 20- 25°C (68-77°F)

            Oral solution

            • Store between 20- 25°C (68-77°F); excursion permitted to 15-30°C (59- 86°F) permitted Do not freeze
            • Dispense in a tight container
            • Discard 10 days after opening container
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Likmez oral
            -
            500 mg/5 mL suspension
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            375 mg capsule
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            250 mg tablet
            metronidazole oral
            -
            500 mg tablet
            metronidazole oral
            -
            500 mg tablet
            Nuvessa vaginal
            -
            1.3 % (65 mg/5 gram) gel
            Flagyl oral
            -
            500 mg tablet
            Flagyl oral
            -
            375 mg capsule
            MetroLotion topical
            -
            0.75 % lotion
            MetroCream topical
            -
            0.75 % cream
            Metrogel topical
            -
            1 % gel
            Noritate topical
            -
            1 % cream
            metronidazole vaginal
            -
            0.75 % (37.5mg/5 gram) gel
            metronidazole vaginal
            -
            0.75 % (37.5mg/5 gram) gel
            metronidazole vaginal
            -
            0.75 % (37.5mg/5 gram) gel
            Rosadan topical
            -
            0.75 % gel
            Rosadan topical
            -
            0.75 % kit
            Rosadan topical
            -
            0.75 % cream
            Rosadan topical
            -
            0.75 % gel
            metronidazole topical
            -
            0.75 % gel
            metronidazole topical
            -
            0.75 % lotion
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            0.75 % gel
            metronidazole topical
            -
            0.75 % cream
            metronidazole topical
            -
            0.75 % gel
            metronidazole topical
            -
            0.75 % cream
            metronidazole topical
            -
            0.75 % cream
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            0.75 % cream
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            0.75 % gel
            metronidazole topical
            -
            0.75 % lotion
            metronidazole topical
            -
            1 % gel
            metronidazole topical
            -
            1 % gel
            Vandazole vaginal
            -
            0.75 % (37.5mg/5 gram) gel

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Select a drug:
            Patient Education
            metronidazole oral

            METRONIDAZOLE - ORAL

            (MET-roe-NID-a-zole)

            COMMON BRAND NAME(S): Flagyl, Likmez

            USES: Metronidazole is an antibiotic that is used to treat a wide variety of infections. It works by stopping the growth of certain bacteria and parasites.This antibiotic treats only certain bacterial and parasitic infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.Metronidazole may also be used with other medications to treat certain stomach/intestinal ulcers caused by a bacteria (H. pylori).

            HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking metronidazole and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor. To prevent stomach upset, take this medication with food or a full glass of water or milk.If you are using the suspension form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.The dosage is based on your medical condition and response to treatment. In children, the dose is also based on weight.For the best effect, take this antibiotic at evenly spaced times. To help you remember, take this medication at the same time(s) every day.Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.Tell your doctor if your condition lasts or gets worse.

            SIDE EFFECTS: Dizziness, headache, stomach upset, nausea, vomiting, loss of appetite, diarrhea, constipation, or metallic taste in your mouth may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.This medication may cause your urine to turn darker in color. This effect is harmless and will disappear when the medication is stopped.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: signs of a new infection (such as sore throat that doesn't go away, fever), easy bruising/bleeding, stomach/abdominal pain, painful urination.Get medical help right away if you have any very serious side effects, including: unsteadiness, seizures, mental/mood changes (such as confusion), trouble speaking, numbness/tingling of arms/legs, eye pain, sudden vision changes, headache that is severe or doesn't go away, stiff/painful neck.Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking metronidazole, tell your doctor or pharmacist if you are allergic to it; or to other antibiotics (such as tinidazole); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, certain blood disorders (low blood cell counts), a certain rare genetic disorder (Cockayne syndrome).Avoid alcoholic beverages and products containing propylene glycol while taking this medication and for at least 3 days after finishing this medicine because severe stomach upset/cramps, nausea, vomiting, headache, and flushing may occur.This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Talk to your doctor if you are using marijuana (cannabis).Metronidazole may cause live bacterial vaccines (such as typhoid vaccine) to not work well. Tell your health care professional that you are using metronidazole before having any immunizations/vaccinations.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.This medication passes into breast milk. If you are prescribed the single-dose treatment, your doctor may direct you to stop breast-feeding for a short time after the dose. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also Precautions section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: alcohol-containing products (such as cough and cold syrups, aftershave), products containing propylene glycol, lopinavir/ritonavir solution, lithium.Do not take metronidazole if you are also taking disulfiram or if you have taken disulfiram within the last 2 weeks.This medication may interfere with certain lab tests, possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: nausea, vomiting, unsteadiness.

            NOTES: Do not share this medication with others.If you are being treated for a certain infection (trichomoniasis), all sexual partners may also need to be treated to avoid re-infection. During treatment, avoid sexual intercourse, or always use a latex or polyurethane condom.This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.If you are taking this medication for a longer time, lab tests (such as blood cell counts) may be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Do not freeze the suspension form of this medication. Discard any unused portion of the suspension 10 days after opening the bottle. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised October 2023. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.