Flagyl ER(metronidazole)
BOXED WARNING
Shown to be carcinogenic in mice and rats. Avoid unnecessary use. Should be reserved for the conditions for which it is indicated.

THERAPEUTIC CLASS
Nitroimidazole

 DEA CLASS
RX

 ADULT DOSAGE & INDICATIONS
Bacterial Vaginosis
Nonpregnant Women:
750mg qd for 7 consecutive days

 PEDIATRIC DOSAGE & INDICATIONS
Bacterial Vaginosis
Post-Menarche/Nonpregnant Females:
750mg qd for 7 consecutive days

 DOSING CONSIDERATIONS
Renal Impairment
Hemodialysis: If administration cannot be separated from hemodialysis session, consider supplementation of dosage following the session, depending on patient's clinical situation

Elderly
May need to adjust dose based on serum levels

 ADMINISTRATION
Oral route

Take at least 1 hr ac or 2 hrs pc
Do not split, chew, or crush

 HOW SUPPLIED
Tab, Extended-Release: 750mg

 CONTRAINDICATIONS
Prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives, disulfiram use w/in the last 2 weeks, consumption of alcohol or products containing propylene glycol during and for at least 3 days after therapy.

 WARNINGS/PRECAUTIONS
Cases of encephalopathy and peripheral neuropathy (including optic neuropathy), convulsive seizures, and aseptic meningitis reported; promptly eva luate benefit/risk ratio of the continuation of therapy if abnormal neurologic signs/symptoms appear. Known or previously unrecognized candidiasis may present more prominent symptoms during therapy and requires treatment with a candidacidal agent. Do not administer to patients with severe (Child-Pugh C) hepatic impairment unless benefits outweigh risks. Caution with hepatic/renal impairment, evidence of or history of blood dyscrasia, and in the elderly. Mild leukopenia reported; monitor total and differential leukocyte counts before and after therapy. May result in bacterial resistance if used in the absence of proven or suspected bacterial infection, or a prophylactic indication. Lab test interactions may occur.

 ADVERSE REACTIONS
Headache, vaginitis, nausea, metallic taste, bacterial infection, influenza-like symptoms, genital pruritus, abdominal pain, dizziness, diarrhea, upper respiratory tract infection, rhinitis, sinusitis, pharyngitis, dysmenorrhea.

 DRUG INTERACTIONS
See Contraindications. May potentiate anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in PT prolongation; carefully monitor PT and INR. May increase serum lithium, and may cause lithium toxicity; obtain serum lithium and SrCr levels several days after beginning metronidazole. May increase busulfan concentrations, which can result in increased risk for serious busulfan toxicity; avoid concomitant use, or, if coadministration is medically needed, frequently monitor busulfan concentration and adjust busulfan dose accordingly. Simultaneous administration of drugs that decrease microsomal liver enzyme activity (eg, cimetidine) may prolong T1/2 and decrease clearance. Simultaneous administration of drugs that induce microsomal liver enzymes (eg, phenytoin, phenobarbital) may accelerate elimination, resulting in reduced levels. Impaired clearance of phenytoin reported.

 PREGNANCY AND LACTATION
Category B, not for use in nursing.

 MECHANISM OF ACTION
Nitroimidazole antimicrobial; exerts antibacterial effects in an anaerobic environment. Upon entering the organism, the drug is reduced by intracellular electron transport proteins. Because of this alteration, a concentration gradient is maintained which promotes the drug's intracellular transport. Presumably, free radicals are formed which, in turn, react with cellular components, resulting in death of the bacteria.

 PHARMACOKINETICS
Absorption: (Healthy adults) Cmax=19.4mcg/mL (fed), 12.5mcg/mL (fasted); Tmax=4.6 hrs (fed), 6.8 hrs (fasted); AUC=211mcg•hr/mL (fed), 198mcg•hr/mL (fasted). Distribution: Plasma protein binding (<20%); found in breast milk; crosses the placenta. Metabolism: Side-chain oxidation and glucuronide conjugation; 1-(β-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid (metabolites). Elimination: Urine (60-80%, 20% unchanged), feces (6-15%); (Healthy adults) T1/2=7.4 hrs (fed), 8.7 hrs (fasted).

 ASSESSMENT
Assess for candidiasis, alcohol use, hepatic/renal impairment, evidence/history of blood dyscrasia, hypersensitivity to drug or other nitroimidazole derivatives, pregnancy/nursing status, and possible drug interactions. Obtain total and differential leukocyte counts.

 MONITORING
Monitor for abnormal neurologic signs/symptoms, candidiasis, and other adverse reactions. Monitor total and differential leukocyte counts after therapy. Monitor PT and INR with oral coumarin anticoagulants (eg, warfarin).

 PATIENT COUNSELING
Instruct to d/c consumption of alcoholic beverages or products containing propylene glycol while taking the drug and for at least 3 days afterward. Counsel that therapy should only be used to treat bacterial, not viral (eg, common cold), infections. Instruct to take exactly ud. Inform that skipping doses or not completing full course of therapy may decrease effectiveness of treatment and increase bacterial resistance.

 STORAGE
25°C (77°F); excursions permitted to 15-30°C (59-86°F). Store in a dry place.