RIFAMPIN

RIFAMPIN
(rif'am-pin)
Rifadin, Rimactane, Rofact 
Classifications: antibiotic; antituberculosis agent;
Therapeutic: antibiotic
; antituberculosis agent
Pregnancy Category: C

Availability

150 mg, 300 mg capsules; 600 mg injection

Action

Semisynthetic derivative of rifamycin B, an antibiotic derived from Streptococcus mediterranei, with bacteriostatic and bactericidal actions. Inhibits DNA-dependent RNA polymerase activity in susceptible bacterial cells, thereby suppressing RNA synthesis.

Therapeutic Effect

Active against Mycobacterium tuberculosis, M. leprae, Neisseria meningitidis, and a wide range of gram-negative and gram-positive organisms.

Uses

Primarily as adjuvant with other antituberculosis agents in initial treatment and retreatment of clinical tuberculosis; as short-term therapy to eliminate meningococci from nasopharynx of asymptomatic carriers of N. meningitidis when risk of meningococcal meningitis is high.

Unlabeled Uses

Chemoprophylaxis in contacts of patients with Haemophilus influenzae type b infection; alone or in combination with dapsone and other antiinfectives in treatment of leprosy (especially dapsone-resistant leprosy). Also infections caused by susceptible gram-negative and gram-positive bacteria that fail to respond to other antiinfectives; in combination with erythromycin or tetracycline for treatment of Legionnaire's disease.

Contraindications

Hypersensitivity to rifampin; obstructive biliary disease; meningococcal disease; intermittent rifampin therapy; pregnancy (category C). Safe use in children <5 y is not established.

Cautious Use

Hepatic disease; history of alcoholism; concomitant use of other hepatotoxic agents.

Route & Dosage

Pulmonary Tuberculosis
Adult: PO/IV 600 mg daily in conjunction with other antituberculosis agents
Child: PO/IV 10–20 mg/kg/d (max: 600 mg/d)

Meningococcal Carriers
Adult: PO 600 mg q12h for 2 consecutive days
Child: PO 10–20 mg/kg q12h for 2 consecutive days (max: 600 mg/d)

Prophylaxis for H. influenzae Type B
Adult: PO 600 mg/d for 4 d
Child: PO 20 mg/kg/d for 4 d (max: 600 mg/d)

Dapsone-Sensitive Multibacillary Leprosy
Adult: PO 600 mg once/mo with clofazimine and dapsone for a minimum of 2 y

Administration

Oral
  • Give 1 h before or 2 h after a meal. Peak serum levels are delayed and may be slightly lower when given with food; capsule contents may be emptied into fluid or mixed with food.
  • Note: An oral suspension can be prepared from capsules for use with pediatric patients. Consult pharmacist for directions.
  • Keep a desiccant in bottle containing capsules to prevent moisture causing instability.
Intravenous

PREPARE: IV Infusion: Dilute by adding 10 mL of sterile water for injection to each 600-mg vial to yield 60 mg/mL. Swirl to dissolve. Withdraw the ordered dose and further dilute in 500 mL of D5W (preferred) or NS. If absolutely necessary, 100 mL of D5W or NS may be used.  

ADMINISTER: IV Infusion: Infuse 500 mL solution over 3 h and 100 mL solution over 30 min. Note: A less concentrated solution infused over a longer period is preferred.  

INCOMPATIBILITIES Solution/additive: Minocycline. Y-site: Diltiazem.

  • Use NS solutions within 24 h and D5W solutions within 4 h of preparation.

Adverse Effects (≥1%)

CNS: Fatigue, drowsiness, headache, ataxia, confusion, dizziness, inability to concentrate, generalized numbness, pain in extremities, muscular weakness. Special Senses: Visual disturbances, transient low-frequency hearing loss, conjunctivitis. GI: Heartburn, epigastric distress, nausea, vomiting, anorexia, flatulence, cramps, diarrhea, pseudomembranous colitis, transient elevations in liver function tests (bilirubin, BSP, alkaline phosphatase, ALT, AST), pancreatitis. Hematologic: Thrombocytopenia, transient leukopenia, anemia, including hemolytic anemia. Body as a Whole: Hypersensitivity (fever, pruritus, urticaria, skin eruptions, soreness of mouth and tongue, eosinophilia, hemolysis), flu-like syndrome. Urogenital: Hemoglobinuria, hematuria, acute renal failure, light-chain proteinuria, menstrual disorders, hepatorenal syndrome, (with intermittent therapy). Respiratory: Hemoptysis. Other: Increasing lethargy, liver enlargement and tenderness, jaundice, brownish-red or orange discoloration of skin, sweat, saliva, tears, and feces; unconsciousness.

Diagnostic Test Interference

Rifampin interferes with contrast media used for gallbladder study; therefore, test should precede daily dose of rifampin. May also cause retention of BSP. Inhibits standard assays for serum folate and vitamin B12.

Interactions

Drug: Alcohol, isoniazid, pyrazinamide, ritonavir, saquinavir increase risk of drug-induced hepatotoxicity (including fatal hepatotoxicity when used for latent TB); p-aminosalicylic acid (PAS) decreases concentrations of rifampin; decreases concentrations of alfentanil, alosetron, alprazolam, amprenavir, barbiturates, benzodiazepines, carbamazepine, atovaquone, cevimeline, chloramphenicol, clofibrate, corticosteroids, cyclosporine, dapsone, delavirdine, diazepam, digoxin, diltiazem, disopyramide, estazolam, estramustine, fentanyl, fosphenytoin, fluconazole galantamine, indinavir, itraconazole, ketoconazole, lamotrigine, levobupivacaine, lopinavir, methadone, metoprolol, mexiletine, midazolam, nelfinavir, oral sulfonylureas, oral contraceptives, phenytoin, progestins, propafenone, propranolol, quinidine, quinine, ritonavir, sirolimus, theophylline, thyroid hormones, tocainide, tramadol, verapamil, warfarin, zaleplon, and zonisamide, leading to potential therapeutic failure.

Pharmacokinetics

Absorption: Readily from GI tract. Peak: 2–4 h. Distribution: Widely distributed, including CSF; crosses placenta; distributed into breast milk. Metabolism: In liver to active and inactive metabolites; is enterohepatically cycled. Elimination: Up to 30% in urine, 60–65% in feces. Half-Life: 3 h.

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Periodic liver function tests are advised. Closely monitor patients with hepatic disease.
  • Check prothrombin time daily or as necessary to establish and maintain required anticoagulant activity when patient is also receiving an anticoagulant.

Patient & Family Education

  • Do not interrupt prescribed dosage regimen. Hepatorenal reaction with flu-like syndrome has occurred when therapy has been resumed following interruption.
  • Be aware that drug may impart a harmless red-orange color to urine, feces, sputum, sweat, and tears. Soft contact lenses may be permanently stained.
  • Report onset of jaundice, hypersensitivity reactions, and persistence of GI adverse effects to physician.
  • Use or add barrier contraceptive if using hormonal contraception. Concomitant use of rifampin and oral contraceptives leads to decreased effectiveness of the contraceptive and to menstrual disturbances (spotting, breakthrough bleeding).
  • Keep drug out of reach of children.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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