Usage
Rifabutin is an antibiotic primarily used for the prevention and treatment of infections caused by Mycobacterium avium complex (MAC) in patients with advanced HIV infection. It is also used, in combination with other antitubercular agents, for the treatment of active tuberculosis, particularly in cases of multidrug-resistant tuberculosis. It belongs to the rifamycin class of antibiotics.
Rifabutin inhibits bacterial DNA-dependent RNA polymerase, thus suppressing RNA synthesis and leading to bacterial cell death.
Alternate Names
The generic name is rifabutin. Common brand names include Mycobutin.
How It Works
Pharmacodynamics: Rifabutin inhibits bacterial DNA-dependent RNA polymerase, preventing RNA synthesis and causing bacterial cell death. It exhibits activity against a range of mycobacterial species, including M. avium and M. tuberculosis.
Pharmacokinetics:
- Absorption: Rifabutin is well-absorbed orally, with bioavailability enhanced when taken with food.
- Metabolism: Primarily metabolized in the liver, with involvement of CYP3A4 enzymes.
- Elimination: Excreted in urine, feces, and bile. The reddish-orange color of these excretions is a harmless side effect due to the drug and its metabolites.
Mode of Action: Rifabutin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase. This binding blocks the initiation of RNA synthesis, leading to inhibition of protein synthesis and ultimately bacterial cell death.
Elimination Pathways: Rifabutin is primarily eliminated via hepatic metabolism and biliary excretion, with some renal excretion.
Dosage
Standard Dosage
Adults:
- MAC Prophylaxis: 300 mg once daily or 150 mg twice daily with food.
- Active Tuberculosis: 5 mg/kg (up to 300 mg) daily, usually as part of a combination therapy.
Children:
Data on pediatric use are limited. Dosing is generally based on weight (5 mg/kg up to a maximum of 300 mg daily), but its safety and effectiveness in children have not been fully established.
Special Cases:
- Elderly Patients: Initiate at the lower end of the dosing range due to potential age-related decline in organ function.
- Patients with Renal Impairment: For severe renal impairment (creatinine clearance <30 mL/min), reduce the dose by 50%.
- Patients with Hepatic Dysfunction: Dose adjustments may be needed in severe hepatic impairment, but specific guidelines are not available.
- Patients with Comorbid Conditions: Close monitoring and dosage adjustments are necessary when co-administered with drugs metabolized by CYP3A4.
Clinical Use Cases
Rifabutin is not typically used in the clinical settings of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary role is in the management of mycobacterial infections.
Dosage Adjustments
Dose modifications are necessary based on renal/hepatic function, concomitant medications (especially CYP3A4 inhibitors or inducers), and patient response.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, abdominal pain, loss of appetite, headache, skin rash, itching, discoloration of urine, sweat, tears, and other bodily fluids to a reddish-orange color (harmless and reversible).
Rare but Serious Side Effects:
Uveitis (eye inflammation), neutropenia (low neutrophil count), thrombocytopenia (low platelet count), leukopenia (low white blood cell count), anemia, hepatitis, severe skin reactions.
Long-Term Effects:
Discoloration of soft contact lenses (permanent), peripheral neuropathy (with prolonged use), Clostridium difficile infection.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis, angioedema), drug-induced hepatitis, severe cutaneous adverse reactions (SCARs).
Contraindications
Hypersensitivity to rifabutin or any other rifamycin antibiotics. Concurrent use with certain antiretroviral drugs (e.g., rilpivirine).
Drug Interactions
Rifabutin is a potent inducer and substrate of CYP3A4. It can interact with numerous medications, including:
- Antiretrovirals: Protease inhibitors, non-nucleoside reverse transcriptase inhibitors.
- Azole antifungals: Fluconazole, itraconazole, ketoconazole.
- Macrolide antibiotics: Clarithromycin, erythromycin.
- Other: Oral contraceptives, anticoagulants, anticonvulsants.
Consult a drug interaction database for a comprehensive list.
Pregnancy and Breastfeeding
Limited data exist regarding use during pregnancy. While animal studies haven’t shown teratogenicity, it should be used with caution and only if the potential benefit outweighs the potential risk to the fetus.
It is unknown whether rifabutin is excreted in human milk. A decision should be made whether to discontinue breastfeeding or the drug, considering the potential risks to the infant and the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial DNA-dependent RNA polymerase.
- Side Effects: Nausea, vomiting, diarrhea, rash, discoloration of body fluids; rarely uveitis, neutropenia, thrombocytopenia.
- Contraindications: Hypersensitivity to rifamycins; concurrent use with certain antiretrovirals.
- Drug Interactions: Numerous, especially with CYP3A4 substrates and inducers.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: 300 mg once daily (MAC prophylaxis); 5 mg/kg up to 300 mg daily (tuberculosis).
- Monitoring Parameters: Liver function tests, complete blood counts, eye examinations (if uveitis suspected).
Popular Combinations
Often used in combination with other antimycobacterial agents like ethambutol, clarithromycin, or azithromycin for the treatment of MAC infections, or with other antitubercular drugs for the treatment of tuberculosis.
Precautions
Monitor for hematologic abnormalities, liver function, and ocular symptoms (uveitis). Use with caution in patients with renal or hepatic impairment. Rifabutin can reduce the effectiveness of hormonal contraceptives. Advise patients to use alternative methods of birth control.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rifabutin?
A: For MAC prophylaxis in adults, 300 mg once daily or 150 mg twice daily with food. For tuberculosis, 5 mg/kg (up to 300 mg) daily. Pediatric dosing is weight-based (5 mg/kg up to 300 mg daily), but data is limited.
Q2: What is the mechanism of action of Rifabutin?
A: Rifabutin inhibits bacterial DNA-dependent RNA polymerase, suppressing RNA synthesis.
Q3: What are the common side effects of Rifabutin?
A: Nausea, vomiting, diarrhea, rash, and discoloration of body fluids (harmless).
Q4: What are the serious side effects of Rifabutin?
A: Uveitis, neutropenia, thrombocytopenia, and hepatitis.
Q5: What are the contraindications to Rifabutin?
A: Hypersensitivity to rifamycins, concurrent use with certain antiretroviral drugs.
Q6: Does Rifabutin interact with other drugs?
A: Yes, it interacts with many drugs, notably those metabolized by CYP3A4.
Q7: Can Rifabutin be used in pregnant or breastfeeding women?
A: Use with caution if benefits outweigh risks; its safety has not been fully established.
Q8: What monitoring is required during Rifabutin therapy?
A: Liver function tests, complete blood counts, and eye examinations (if indicated).
Q9: What is the difference between Rifabutin and Rifampin?
A: While both are rifamycins, Rifabutin has fewer drug interactions with antiretrovirals and is often preferred for patients with HIV infection.
Q10: How should Rifabutin be administered?
A: Orally, with or without food. If gastrointestinal side effects occur, administer with food.
