rifampin

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; enters CSF.

Protein Binding: 80%.

Metabolism/Excretion: Mostly metabolized by the liver; 60% eliminated in feces via biliary elimination.

Half-Life: 3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2–4 hr	12–24 hr
IV	rapid	end of infusion	12–24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of atazanavir, darunavir, fosamprenavir, lurasidone, praziquantel, or tipranavir.

Use Cautiously in:

History of liver disease (↑ risk of hepatotoxicity);
Chronic liver disease, poor nutritional status, or prolonged use of antibacterial drugs or anticoagulants (↑ risk of vitamin K deficiency and subsequent coagulation disorders);
Diabetes;
Concurrent use of other hepatotoxic agents;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: red discoloration of tears

GI: abdominal pain, diarrhea, flatulence, heartburn, nausea, vomiting, HEPATOTOXICITY, red discoloration of saliva and teeth

GU: red discoloration of urine

Hemat: bleeding, hemolytic anemia, thrombocytopenia, THROMBOTIC MICROANGIOPATHY (INCLUDING THROMBOTIC THROMBOCYTOPENIC PURPURA AND HEMOLYTIC UREMIA SYNDROME)

MS: arthralgia, muscle weakness, myalgia

Neuro: ataxia, confusion, drowsiness, fatigue, headache, weakness

Resp: INTERSTITIAL LUNG DISEASE

Misc: flu-like syndrome, HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Significantly ↓ levels and effectiveness of atazanavir, darunavir, fosamprenavir, lurasidone, praziquantel, and tipranavir; concurrent use contraindicated.
Significantly ↓ levels and effectiveness of efavirenz, quinine, sofosbuvir, ticagrelor, and zidovudine; avoid concomitant use.
Significantly ↓ levels and effectiveness of hormonal contraceptives; use nonhormonal birth control during rifampin therapy.
May ↓ levels and effectiveness of numerous drugs, including chloramphenicol, clarithromycin, cyclosporine, diazepam, diltiazem, disopyramide, doxycycline, fluconazole, glipizide, glyburide, haloperidol, ketoconazole, levothyroxine, losartan, lovastatin, metoprolol, mexiletine, morphine, moxifloxacin, nifedipine, nortriptyline, ondansetron, oxycodone, phenytoin, prednisolone, propafenone, propranolol, quinidine, simvastatin, tamoxifen, theophylline, toremifene, verapamil, and zolpidem.
May ↑ levels of active metabolite of clopidogrel, which may ↑ risk of bleeding; avoid concomitant use.
May ↓ levels and effectiveness of warfarin; monitor INR regularly during concurrent therapy.
May significantly ↓ levels and effectiveness of itraconazole; avoid use 2 wk before and during itraconazole therapy.
May significantly ↓ levels and effectiveness of irinotecan; avoid use 2 wk before and during irinotecan therapy.
May ↓ levels and effectiveness of digoxin; closely monitor serum digoxin concentrations and ↑ digoxin dose by 20–40%, if needed.
May significantly ↓ levels and effectiveness of tacrolimus; monitor tacrolimus whole blood concentrations regularly and ↑ tacrolimus dose as necessary.
May ↓ levels and effectiveness of methadone, which may ↑ risk of withdrawal symptoms.
Absorption may be ↓ by antacids; administer rifampin ≥1 hr prior to antacids.
Probenecid and trimethoprim/sulfamethoxazole may ↑ levels and risk of toxicity.
Concurrent use with atovaquone may ↓ atovaquone levels and effectiveness and ↑ levels and risk of toxicity of rifampin; avoid concomitant use.
May ↓ levels and effectiveness of dapsone; may also ↑ levels and toxicity of the active metabolite of dapsone, which could ↑ the risk of methemoglobinemia.

Route/Dosage ⬆ ⬇

Tuberculosis

PO IV (Adults ): 600 mg/day or 10 mg/kg/day (up to 600 mg/day) single dose; may also be given twice weekly.
PO IV (Children and Infants): 10–20 mg/kg/day single dose or divided every 12 hr (not to exceed 600 mg/day); may also be given twice weekly.

Asymptomatic Carriers of Meningococcus

PO IV (Adults ): 600 mg every 12 hr for 2 days.
PO IV (Children ≥1 mo): 10 mg/kg every 12 hr for 2 days (max: 600 mg/dose).
PO (Infants <1 mo): 5 mg/kg every 12 hr for 2 days.

H. influenzae Prophylaxis

PO (Adults ): 600 mg/day for 4 days.
PO (Children ): 20 mg/kg/day for 4 days (max: 600 mg/dose).
PO (Neonates ): 10 mg/kg/day for 4 days.

Synergy for S. aureus Infections

PO (Adults ): 300–600 mg twice daily.
PO (Children and Neonates): 5–20 mg/kg/day divided every 12 hr (max: 600 mg/dose).

Availability ⬆ ⬇

(Generic available)

Capsules: 150 mg; 300 mg
Powder for injection: 600 mg/vial

Assessment ⬆ ⬇

Perform mycobacterial studies and susceptibility tests prior to and periodically during therapy to detect possible resistance.
Assess lung sounds and character and amount of sputum periodically during therapy.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Monitor for signs and symptoms of hypersensitivity reactions (fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases), or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). Discontine rifampin if symptoms occur.

Lab Test Considerations:

Evaluate renal function, CBC, and urinalysis periodically and during therapy.
- Monitor hepatic function at least monthly during therapy. May cause ↑ BUN, AST, ALT, and serum alkaline phosphatase, bilirubin, and uric acid concentrations.
- May cause false-positive direct Coombs’ test results. May interfere with folic acid and vitamin B assays.
- May interfere with dexamethasone suppression test results; discontinue rifampin 15 days prior to test.
- May interfere with methods for determining serum folate and vitamin B levels and with urine tests based on color reaction.
- Monitor coagulation tests (PT, INR, aPTT) during therapy in patients at risk for vitamin K deficiency.

Implementation ⬆ ⬇

Do not confuse rifampin with rifaximin or Rifamate.
May use vitamin K supplementation in patients at risk for vitamin K deficiency.
PO: Administer medication on an empty stomach at least 1 hr before or 2 hr after meals with a full glass (240 mL) of water. If GI irritation becomes a problem, may be administered with food. Antacids may also be taken 1 hr prior to administration. Capsules may be opened and contents mixed with applesauce or jelly for patients with difficulty swallowing.
- Pharmacist can compound a syrup for patients unable to swallow solids.

IV Administration:

Avoid extravasation; may cause local irritation and inflammation due to extravascular infiltration of the infusion. If these occur, discontinue infusion and restart at another site.
IV doses are the same doses as oral.
Intermittent Infusion: Reconstitution: Reconstitute each 600-mg vial with 10 mL of sterile water for injection for a concentration of 60 mg/mL. Swirl gently to dissolve. Diluent: Dilute further in 100 mL or 500 mL of D5W or 0.9% NaCl. Reconstituted vials are stable for 24 hr at room temperature. Infusion is stable at room temperature for 4 hr (in D5W) or 24 hr (in 0.9% NaCl).Concentration: Not to exceed 60 mg/mL.
Rate: Administer solutions diluted in 100 mL over 30 min and solutions diluted in 500 mL over 3 hr.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication once daily (unless biweekly regimens are used), as directed, and not to skip doses or double up on missed doses. Emphasize the importance of continuing therapy even after symptoms have subsided. Length of therapy for tuberculosis depends on regimen being used and underlying disease states. Patients on short-term prophylactic therapy should also be advised of the importance of compliance with therapy.
Advise patient to notify health care professional promptly if signs and symptoms of hepatitis (yellow eyes and skin, nausea, vomiting, anorexia, unusual tiredness, weakness) or of thrombocytopenia (unusual bleeding or bruising) occur.
Caution patient to avoid the use of alcohol during this therapy, because this may increase the risk of hepatotoxicity.
Instruct patient to report the occurrence of flu-like symptoms (fever, chills, myalgia, headache) promptly.
Rifampin may occasionally cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Inform patient that saliva, sputum, teeth, sweat, tears, urine, and feces may become red-orange to red-brown and that soft contact lenses may become permanently discolored.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
Emphasize the importance of regular follow-up exams to monitor progress and to check for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇