Rifabutin

Registered South African indications:

• Pulmonary tuberculosis caused by M. tuberculosis, proven to be sensitive by laboratory tests to rifabutin and resistant to rifampicin
• Infections caused by M. avium intracellulare complex (MAC) or M. xenopi for the treatment of both disseminated and localised disease and also in immunocompromised HIV-infected patients
• Prophylactic treatment of infections caused by M. avium intracellulare complex (MAC) in patients with advanced HIV infection

Registered South African contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Hypersensitivity to other rifamycins (e.g. rifampicin)
• HIV-infected patients taking clarithromycin
• Coadministration with ketoconazole (unless clinically warranted)
• Coadministration with ritonavir
• Coadministration with delavirdine mesylate 400mg, 8hrly

Contraindications registered in other jurisdictions

• Hypersensitivity (or history of hypersensitivity) to the active ingredient or to any of its excipients
• Hypersensitivity (or history of hypersensitivity) to other rifamycins (e.g. rifampicin)
• Pregnancy
• Breastfeeding
• Children

South African recommendations

• Pregnancy
• Breastfeeding
• Severe renal impairment (CrCl <30ml/min)
• Moderate to severe hepatic impairment
• Concomitant use with contact lens
• Coadministration with clarithromycin (or other macrolides) and/or fluconazole (and related compounds)
• Coadministration with protease inhibitors

Recommendations in other jurisdictions

• Severe renal impairment (CrCl <30ml/min)
• Moderate to severe hepatic impairment
• Porphyria
• Active disease caused by pulmonary tuberculosis or other mycobacteria (When used as prophylaxis)
• Concomitant use with contact lens
• Coadministration with clarithromycin (or other macrolides) and/or fluconazole (and related compounds)

Forms avail. in SA and covered in this monograph: cap

Dosages below include:

• South African Standard Treatment Guideline indications and dosages
• South African registered indications and dosages

Infections caused by: Mycobacterium tuberculosis, Mycobacterium avium-intracellulare complex (MAC) or Mycobacterium xenopi

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guideline indications and dosages

Pulmonary tuberculosis treatment (Additional agents required)
- In patients with HIV on atazanavir or darunavir or if double dose lopinavir/ ritonavir is not tolerated (as a replacement for rifampicin)

• Oral (cap): 150mg, daily
  (STG, Adult 2019; PHC 2023)

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South African registered indications and dosages

Newly diagnosed pulmonary tuberculosis caused by M. tuberculosis, proven to be sensitive by laboratory tests to rifabutin and resistant to rifampicin (Additional agents required)
- In combination with other medicines not belonging to the rifamycin group

• Oral (cap): >35kg: 150mg, daily; Treatment duration: 6 months

Chronic, multidrug-resistant pulmonary tuberculosis (Additional agents required)
- In combination regimens

• Oral (cap): >35kg: 300-450mg, daily; Treatment duration: Up to 6 months after negative sputum cultures are obtained

Atypical mycobacterial infections caused by M. avium intracellulare complex (MAC) or M. xenopi (Additional agents required)
- In combination regimens for the treatment of both disseminated and localised disease and also in immunocompromised HIV-infected patients

• Oral (cap): >35kg: 450-600mg, daily; Treatment duration: Up to 6 months after negative sputum cultures are obtained

Prophylaxis of infections caused by M. avium intracellulare complex (MAC) in patients with advanced HIV infections (Additional agents required)
- In combination regimens

• Oral (cap): >35kg: 300mg, daily

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Rifabutin can be administered as a single daily dose, independent of meals

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In all cases rifabutin is to be administered in combination regimens

Not established for use in children and adolescents 

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy

South African recommendations

• Caution; not recommended
• Safety in pregnancy has not been established

Recommendations in other jurisdictions

• Contraindicated
• 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

Breastfeeding

South African recommendations

• Caution; not recommended
• Safety in breastfeeding has not been established

Recommendations in other jurisdictions

• Contraindicated
• Due to lack of data, as a precautionary measure, rifabutin should not be administered those breastfeeding children even though in experimental animal studies the drug was not teratogenic

Renal Impairment

• Mild to Moderate (CrCl ≥30ml/min: No dose adjustment recommended
• Severe (CrCl <30ml/min): Caution; dose adjustment recommended
  Reduce dose by 50%

Hepatic Impairment

South African recommendations

• Mild: No dosage adjustment recommended
• Moderate: Caution; no information available
• Severe: Caution; dose adjustment recommended
  For patients with severe liver insufficiency a dose reduction should be considered

Recommendations in other jurisdictions

• Mild: No dosage adjustment recommended
• Moderate: Caution; no information available
• Severe: Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)
  Nausea is a common side effect that may be potentially porphyrinogenic through the reduction in carbohydrate intake and can be confused with an acute porphyria attack

Drugs in Sport

• Permitted - No warnings

Respiratory Disorders

• Chest pressure or pain with dyspnoea

Gastrointestinal Disorders

• Nausea and vomiting
• Clostridium difficile associated diarrhoea (CDAD) 

Hepatobiliary Disorders

• Jaundice
• Increased hepatic enzymes
• Hepatitis

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Skin discolouration
• Rash

Immune, Blood and Lymphatic System Disorders

• Leukopenia
• Anaemia
• Pancytopenia
• Agranulocytosis
• Lymphopenia
• Granulocytopenia
• Neutropenia
• Decreased white blood cell count
• Decreased neutrophil count
• Thrombocytopenia
• Decreased platelet count
• Hypersensitivity
• Bronchospasm
• Eosinophilia
• Fever
• Haemolysis

Sensory Disorders

• Uveitis
• Corneal deposits

Others

• Flu-like syndrome
• Red-orange colour to the urine and body secretions

• Cytochrome P450 3A substrates
• Analgesics
• Anticoagulants
• Corticosteroids
• Cyclosporin
• Digitalis (although not digoxin)
• Oral hypoglycaemic agents
• Narcotics
• Phenytoin
• Quinidine
• P-aminosalicylic acid
• Amprenavir
• Fosamprenavir/ritonavir
• Indinavir
• Lopinavir/ritonavir
• Saquinavir
• Ritonavir
• Tipranavir/ritonavir
• Itraconazole
• Posaconazole
• Voriconazole
• Ketoconazole
• Miconazole
• Dapsone
• Sulfamethoxazole-Trimethoprim
• Clarithromycin
• Oral contraceptives
• Tacrolimus
• Delavirdine mesylate (400mg, 8hrly)

• Full blood count with differential
• Platelet count
• Hepatic function

Additional observations

• Signs and symptoms of
  - Hypersensitivity
  - Uveitis
• Severe cutaneous adverse reactions

Coadministration with other anti-mycobacterial drugs

• In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, rifabutin should always be given in combination with other anti-mycobacterial drugs not belonging to the family of rifamycins

Rifabutin is a semi-synthetic ansamycin antibiotic. It inhibits incorporation of thymidine into the DNA of M. tuberculosis. Rifabutin was seen to be active against non-tuberculous (atypical) mycobacteria including M. avium-intracellulare (MAC) in vitro as well as in experimental infections caused by these pathogens in immunodeficient mice.

Spectrum of activity: Mycobacterium tuberculosis, Mycobacterium avium-intracellulare complex (MAC) or Mycobacterium xenopi

Capsule 150mg

• Mycobutin (Pfizer) originator