Mycobutin

/ Pfizer

Rifabutin is generally administered as a single, daily, oral dose at any time independently of meals.
Adults: Rifabutin as a single agent: Prophylaxis of MAC infection in immune-depressed patients:  300 mg (2 capsules).
Rifabutin in combination regimens: Non-tuberculous mycobacterial disease:  450-600 mg (3 to 4 capsules) for up to 6 months after negative cultures are obtained.
MAC treatment: When Rifabutin is given in association with clarithromycin, the dosage of Rifabutin should be reduced to 300 mg after the first month of treatment.
Pulmonary tuberculosis: 150 mg daily (1 capsule), for 6-9 months, or for at least 6 months after negative cultures are obtained.  This dosage should be increased to 300-450 mg/day in patients previously treated with anti-tuberculous drugs.
Paediatric population: There are inadequate data to support the use of Rifabutin in children at the present time.
Elderly: No specific recommendations for dosage alterations in the elderly are suggested.

Chronic tuberculosis where there is firm evidence of acid fast bacteria resistent to Rifampicin or to two other alternative drugs.
Treatment of infections caused by MAC or other atypical mycobacteria where there is evidence of resistant bacteria as above.
Treatment of infections caused by MAC or other atypical mycobacteria in AIDS patients in all cases not subject to the above restrictions.
Prevention of MAC infections in AIDS patients whose CD4 counts lower or eqval to 200mm³.

* Hypersensitivity or history of hypersensitivity to the active substance, other rifamycins (e.g. rifampicin) or to any of the excipients.
* Concomitant use with rilpivirine containing prolonged-release suspension for injection is contraindicated.
* Pregnant and breast-feeding women and in children, Rifabutin should not be used in these patients due to insufficient clinical experience.

* Before starting rifabutin prophylaxis, patients should be assessed to ensure that they do not have active disease caused by pulmonary tuberculosis or other mycobacteria.
Prophylaxis against MAC infection may need to be continued throughout the patient’s lifetime.
* 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.
* Mild hepatic impairment does not require a dose modification. This medicinal product should be used with caution in cases of severe liver insufficiency. Mild to moderate renal impairment does not require any dosage adjustment.
Severe renal impairment (creatinine clearance below 30 ml/min) requires a dosage reduction of 50%.
* It is recommended that white blood cell and platelet counts and liver enzymes be monitored periodically during treatment.
* When rifabutin is used concomitantly with clarithromycin for MAC treatment, a decreased dose of rifabutin is recommended due to the increase in plasma concentrations of rifabutin.
* Because of the possibility of occurrence of uveitis, patients should be carefully monitored when rifabutin is given in combination with clarithromycin (or other macrolides) and/or fluconazole (and related compounds). If such an event occurs, the patient should be referred to an ophthalmologist and, if considered necessary, rifabutin treatment should be suspended.
* Uveitis associated with rifabutin must be distinguished from other ocular complications of HIV.
* HIV protease inhibitors act as substrates or inhibitors of CYP450 3A4 mediated metabolism. Therefore, due to significant drug-drug interactions between protease inhibitors and rifabutin, their concomitant use should be based on the overall assessment of the patient and patient specific drug profile.
* Rifabutin is a CYP450 3A inducer. Therefore, co-administration with antiretroviral medicines including but not limited to bictegravir, elvitegravir, oral rilpivirine, or doravirine and anti-HCV medicines including but not limited to sofosbuvir (alone or in combination) is not recommended due to the expected decrease in plasma concentrations of the antiretrovirals and anti-HCV medicines which may lead to loss of virologic response and possible development of resistance.
* 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.
* There have been reports of severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) with anti-tuberculosis drugs. If patients develop a skin rash they should be monitored closely and suspect drug(s) discontinued if lesions progress.
See prescribing information for full details.

Leucopenia, anemia, pancytopenia, agranulocytosis lymphopenia granulo-cytopenia, neutropenia, thrombocytopenia, nausea, pyrexia.
See prescribing information for full details.

Rifabutin has been shown to induce the enzymes of the cytochrome P450 3A subfamily and therefore may affect the pharmacokinetic behaviour of drugs metabolized by the enzymes belonging to this subfamily.  Upward adjustment of the dosage of such drugs may be required when administered with Rifabutin Similarly, Rifabutin might reduce the activity of analgesics, anticoagulants, corticosteroids, cyclosporin, digitalis (although not digoxin), oral hypoglycaemics, narcotics, phenytoin and quinidine.
Clinical studies have shown that rifabutin does not affect the pharmacokinetics of didanosine (DDI), and isoniazid (however, for the latter refer also to undesirable effects). On the basis of the above metabolic considerations no significant interaction may be expected with ethambutol, theophylline, sulfonamides, pyrazinamide and zalcitabine (DDC).
As p-aminosalicylic acid has been shown to impede GI absorption of rifamycins it is recommended that when it and rifabutin are both to be administered they be given with an interval of 8 – 12 hours.
See prescribing information for full details.

Due to lack of data in pregnant women, as a precautionary measure, this medicinal product should not be administered to pregnant women or those breast-feeding children even though in experimental animal studies the drug was not teratogenic.
See prescribing information for full details.

Gastric lavage and diuretic treatment should be carried out. Supportive care and symptomatic treatment should be administered.

Storage: Store below 25°C.