Chemical formula: C₄₆H₆₂N₄O₁₁ Molecular mass: 847.005 g/mol PubChem compound: 6323490
Rifabutin interacts in the following cases:
Severe renal impairment (creatinine clearance below 30 ml/min) requires a rifabutin dosage reduction of 50%.
Rifabutin should be used with caution in cases of severe liver insufficiency.
Contraceptive cover may not be adequate during concomitant therapy with rifabutin, therefore, patients should be advised to use other methods of contraception.
A 50% reduction in the rifabutin dose is recommended when combined with amprenavir. Increased monitoring for adverse reactions is warranted.
Effect on rifabutin: 2.9-fold ↑ AUC, 2.2-fold ↑ Cmax
Effect on rifabutin: Approx. 77% increase in AUC.
Effect on clarithromycin: Approx. 50% decrease in AUC.
Effect on rifabutin: 82% increase in AUC.
Dosage reduction of rifabutin by at least 75% (to 150 mg every other day or three times per week) is recommended when combined with fosamprenavir.
Effect on rifabutin: 64% ↑ AUC (Drug plus active metabolite)
Dose reduction of rifabutin to half the standard dose and increase of indinavir to 1000 mg every 8 hours are recommended when rifabutin and indinavir are coadministered.
Effect on rifabutin: 173% ↑ in AUC, 134% ↑ Cmax
Effect on indinavir: 34% ↓ in AUC, 25% ↓ in Cmax
A case report indicates an increase in rifabutin serum levels in the presence of itraconazole.
Effect on itraconazole: 70-75% decrease in Cmax and AUC.
Co-administered medications, such as ketoconazole, that competitively inhibit the Cyt P450IIIA activity may increase circulating drug levels of rifabutin.
Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e. a maximum dose of 150 mg every other day or three times per week). Increased monitoring for adverse reactions is warranted. Further dosage reduction of rifabutin may be necessary.
Effect on rifabutin: 5.7-fold ↑ AUC, 3.4 fold ↑ Cmax (Drug plus active metabolite)
Co-administration of posaconazole with rifabutin increases rifabutin plasma concentrations and decreases posaconazole plasma concentrations. Concomitant use of rifabutin and posaconazole should be avoided unless the benefit to the patient outweighs the risk. However, if concomitant administration is required, close monitoring of breakthrough fungal infections as well as frequent monitoring for adverse reactions due to increased rifabutin plasma concentrations (e.g. uveitis, leukopenia) are recommended.
Effect on rifabutin: 31% ↑ Cmax, 72% ↑ AUC.
Effect on posaconazole: 43% ↓ Cmax, 49% ↓ AUC.
Due to this multifold increase in rifabutin concentrations and the subsequent risk of side effects, patients requiring both rifabutin and a protease inhibitor, other protease inhibitors should be considered.
Effect on rifabutin: 4-fold increase in AUC, 2.5-fold increase in Cmax
Rifabutin decreases tacrolimus trough blood levels.
Therapeutic drug monitoring of rifabutin is recommended. Coadministration of tipranavir with rifabutin may increase concentrations of rifabutin and its metabolite. Reduce rifabutin dose 75% (e.g. 150 mg every other day) and increase monitoring.
Effect on rifabutin: 2.9-fold ↑ AUC, 1.7-fold ↑ Cmax.
If the benefit outweighs the risk, rifabutin may be coadministered with voriconazole if the maintenance dose of voriconazole is increased to 5 mg/kg intravenously every 12 hours or from 200 mg to 350 mg orally, every 12 hours (100 mg to 200 mg orally, every 12 hours in patients less than 40 kg). Careful monitoring of full blood counts and adverse events to rifabutin (e.g. uveitis) is recommended when rifabutin is coadministered with voriconazole.
Effect on rifabutin: 195% ↑ Cmax, 331% ↑ AUC (voriconazole dosed at 400 mg twice daily)
Rifabutin (300 mg once daily) decreased the Cmax and AUC of voriconazole at 200 mg twice daily by 69% and 78%, respectively. During co-administration with rifabutin, the Cmax and AUC of voriconazole at 350 mg twice daily were 96% and 68% of the levels when administered alone at 200 mg twice daily. At a voriconazole dose of 400 mg twice daily Cmax and AUC were 104% and 87% higher, respectively, compared with voriconazole alone at 200 mg twice daily.
Effect on zidovudine: Approx. 32% decrease in Cmax and AUC.
A large clinical study has shown that these changes are of no clinical relevance.
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including rifabutin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Rifabutin may impart a red-orange colour to the urine and possibly to skin and body secretions. Contact lenses, especially soft, may be permanently stained.
Due to lack of data in pregnant women, as a precautionary measure, rifabutin should not be administered to pregnant women even though in experimental animal studies the drug was not teratogenic.
Rifabutin may interact with oral contraceptives.
Due to lack of data in pregnant women, as a precautionary measure, rifabutin should not be administered to women breast-feeding children even though in experimental animal studies the drug was not teratogenic.
There have been no reports of adverse effects on ability to drive and use machines.
The tolerability of rifabutin in multiple drug regimens, was assessed in both immunocompetent and immunocompromised patients, suffering from tuberculosis and non-tuberculous mycobacteriosis in long term studies with daily dosages up to 600 mg.
Bearing in mind that rifabutin was often given in these studies as part of a multidrug regimen it is not always possible to define with certainty a drug-event relationship. Treatment discontinuation was necessary only in a very few cases. Adverse reactions identified through clinical trials or post-marketing surveillance by system organ class (SOC) are listed below in the following frequencies, very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100, rare ≥1/10,000 to <1/1,000, very rare <1/10,000 and ‘not known’.
Very common: Leukopenia
Common: Anaemia
Uncommon: Pancytopenia, Agranulocytosis, Lymphopenia, Granulocytopenia, Neutropenia, White blood cell count decreased, Neutrophil count decreased, Thrombocytopenia, Platelet count decreased
Common: Rash
Uncommon: Hypersensitivity, Bronchospasm, Eosinophilia
Uncommon: Uveitis, Corneal deposits
Common: Nausea
Uncommon: Vomiting
Uncommon: Jaundice, Hepatic enzyme increased
Uncommon: Skin discolouration
Common: Myalgia
Uncommon: Arthralgia
Common: Pyrexia
Clostridium difficile colitis is a mandated adverse reaction for the pharmacological class; this event was neither observed in the clinical trials nor in the spontaneous reporting for rifabutin.
Anaphylactic shock has occurred with other antibiotics of the same class.
Mild to severe, reversible uveitis has been reported less frequently when rifabutin is used at 300 mg as monotherapy in MAC prophylaxis, versus rifabutin in combination with clarithromycin (or other macrolides) for MAC treatment.
Flu-like syndrome, chest pressure or pain with dyspnoea and rarely hepatitis and haemolysis has been reported.
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