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Rifampin

Pronouncation: (RIFF-am-pin)
Class: Antituberculosis agent

Trade Names:
Rifadin
- Capsules 150 mg
- Capsules 300 mg
- Powder for injection 600 mg

Trade Names:
Rimactane
- Capsules 300 mg

Rofact (Canada)

Pharmacology

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Meningococcal Meningitis Prophylaxis	Be the first to rate it 0 comments
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Inhibits DNA-dependent RNA polymerase in susceptible strains of bacteria.

Pharmacokinetics

Absorption

Almost completely absorbed (oral). T _max is 1 to 4 h (oral). C _max is 7ߙmcg/mL (oral average), may vary 4 to 32ߙmcg/mL (oral adults); 3.5 to 15 mcg/mL (oral, children); 9 to 17 mcg/mL (IV). Absorption decreased 30% when taken with food.

Distribution

Vd is about 0.64 L/kg (600 mg IV); 0.66 L/kg (300 mg IV). Diffuses well into most body tissues and fluids, including CSF. Crosses placenta and distributes into breast milk. Protein binding is 89%.

Metabolism

Metabolized in liver by deacetylation to active metabolite 25-0-desacetylrifampin. Undergoes enterohepatic circulation.

Elimination

Primarily through bile/fecal (60% to 65% in feces); renal (6% to 15% excreted as unchanged, 15% excreted as active metabolites, 7% as inactive metabolites).

Indications and Usage

Adjunctive treatment of tuberculosis; short-term management to eliminate meningococci from nasopharynx in Neisseria meningitidis carriers.

Unlabeled Uses

Treatment of infections caused by Staphylococcus aureus and Staphylococcus epidermidis ; treatment of gram-negative bacteremia in infancy; treatment of Legionella ; management of leprosy; prophylaxis of Haemophilus influenzae meningitis.

Contraindications

Hypersensitivity to any rifamycin.

Dosage and Administration

Tuberculosis

IV dosage form is for initial treatment or retreatment when drug cannot be taken by mouth.

Adults

PO/IV 10 mg/kg/day (max, 600 mg/day) or 10 mg/kg 2 or 3 times/wk (max, 600 mg).

Children

PO/IV 10 to 20 mg/kg/day (max, 600ߙmg/day) or 10 to 20 mg/kg 2 to 3ߙtimes/wk (max, 600 mg).

Meningococcal Carriers
Adults

PO/IV 600 mg every day for 4 consecutive days.

Children 1 mo or older

PO/IV 10 mg/kg every 12 h for 2 consecutive days.

Children younger than 1 mo

5 mg/kg every 12 h for 2 consecutive days.

Drug Interactions

Azole antifungal agents, benzodiazepines, beta-blockers, buspirone, chloramphenicol, clarithromycin, clozapine, oral contraceptives, corticosteroids, cyclosporine, delavirdine, digitoxin, disopyramide, doxycycline, erythromycin, estrogens, haloperidol, hydantoins, indinavir, losartan, methadone, mexiletine, morphine, nelfinavir, ondansetron, oral anticoagulants, quinidine, quinine, ritonavir, sulfonylureas, tacrolimus, tamoxifen, theophyllines, tocainide, toremifene, tricyclic antidepressants, troleandomycin, verapamil, zolpidem

Therapeutic efficacy may be decreased because of liver enzyme-inducing properties of rifampin.

Digoxin

May decrease digoxin serum concentrations.

Enalapril

May significantly increase BP.

Halothane

Hepatotoxicity and hepatic encephalopathy have been reported with coadministration.

Isoniazid

May result in higher rate of hepatotoxicity.

Ketoconazole

May cause treatment failure of either ketoconazole or rifampin.

Probenecid

Elevates rifampin levels.

Laboratory Test Interactions

May inhibit standard microbiological assays for serum folate and vitamin B ₁₂ . Thus, use alternate assay methods. Transient abnormalities in LFTs (eg, elevation in serum bilirubin, abnormal bromsulfophthalein excretion, alkaline phosphatase, serum transaminases) and reduced biliary excretion of contrast media used for visualization of gallbladder may occur. Therefore, perform these tests before the morning dose of rifampin.

Adverse Reactions

Cardiovascular

Hypotension; shock.

CNS

Headache; drowsiness; fatigue; dizziness; inability to concentrate; mental confusion; generalized numbness; behavioral changes; myopathy.

Dermatologic

Rash; pruritus; urticaria; pemphigoid reaction; flushing.

EENT

Visual disturbances; exudative conjunctivitis.

GI

Heartburn; epigastric distress; anorexia; nausea; vomiting; gas; cramps; diarrhea; sore mouth and tongue; pseudomembranous colitis; pancreatitis.

Genitourinary

Hemoglobinuria; hematuria; renal insufficiency; acute renal failure.

Hematologic

Eosinophilia; transient leukopenia; hemolytic anemia; decreased hemoglobin; hemolysis; thrombocytopenia.

Hepatic

Asymptomatic elevations of liver enzymes and hepatitis.

Respiratory

Shortness of breath; wheezing.

Miscellaneous

Ataxia; muscular weakness; pain in extremities; osteomalacia; myopathy; menstrual disturbances; fever; elevations in BUN; elevated serum uric acid; possible immunosuppression; abnormal growth of lung tumors; reduced 25-hydroxycholecalciferol levels; edema of face and extremities; discoloration of body fluids.

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk. Discontinue nursing or drug.

Hepatic Function

Dosage adjustment is necessary.

Body fluids

Medication may cause harmless red-orange discoloration of urine, feces, saliva, sputum, sweat, and tears. Soft contact lenses may be permanently stained.

Overdosage

Symptoms

Nausea, vomiting, increasing lethargy, unconsciousness, liver enlargement, jaundice, increased direct and total bilirubin levels, altered hepatic enzyme levels.

Patient Information

Instruct patient to take drug on empty stomach, 1 h before or 2ߙh after meals.
Inform patient that body fluids may turn red-orange in color and that soft contact lenses may become permanently stained. Advise patient to wear glasses during course of therapy.
Instruct patient to notify health care provider of persistent anorexia, nausea, vomiting, diarrhea, jaundice, fever, change in color or consistency of stools, malaise or right upper quadrant abdominal pain, unusual bleeding or bruising, petechiae, hematuria, bleeding gums, or pallor.
Tell patient to notify health care provider of drowsiness, fatigue, dizziness, inability to concentrate, confusion, or visual or behavioral changes.
Advise patient who uses oral contraceptives to use nonhormonal form of contraception during therapy.
Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
Advise patient of importance of medication compliance in treatment of tuberculosis. Medication noncompliance reduces efficacy and promotes resistance.
Caution patient to avoid alcohol.