Mycobutin^® (Capsules) Instructions for Use

ATC Code

J04AB04 (Rifabutin)

Active Substance

Rifabutin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic of the rifamycin group. Antituberculosis drug

Pharmacotherapeutic Group

Antibiotic-rifamycin

Pharmacological Action

A semisynthetic antibiotic of the rifamycin group. It has a broad spectrum of action. The mechanism of action is probably associated with the inhibition of amino acid synthesis due to the inhibition of DNA-dependent RNA polymerase.

Rifabutin is active against Mycobacterium tuberculosis (both strains sensitive and resistant to rifampicin), Mycobacterium leprae (both strains sensitive and resistant to rifampicin), and against the Mycobacterium avium complex.

Rifabutin is also active against gram-positive bacteria: Staphylococcus spp. (including polyresistant strains), some strains of Clostridium spp.; gram-negative bacteria: Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Legionella spp., Chlamydia trachomatis; intracellular parasites; some viruses (including HIV-1).

Resistance of pathogen strains to rifabutin develops rapidly.

Pharmacokinetics

It is rapidly absorbed from the gastrointestinal tract. Bioavailability is 20%. C_max in blood plasma is reached in 2-4 hours. Plasma protein binding is 85%. It penetrates the blood-brain barrier. T_1/2 is 45 hours. 30% of rifabutin is excreted in feces, 5% – unchanged in bile, 5% – unchanged in urine, 53% – in urine as metabolites.

Indications

Treatment of infections caused by susceptible microorganisms ( Mycobacterium tuberculosis, MAC complex, other atypical mycobacteria such as Mycobacterium xenopi), including in patients with immunodeficiency. Prophylaxis of infections caused by the MAC complex in patients with immunosuppression, with a CD4 cell count <200 per µl. Treatment of disseminated Mycobacterium avium infection in patients with HIV infection. Tuberculosis (as part of combination therapy).

ICD codes

Dosage Regimen

Administer orally. The dosing regimen is set individually, depending on the indication and the patient’s clinical status.

For the treatment of tuberculosis, the usual adult dose is 150 mg to 300 mg once daily. Always use as part of a multi-drug regimen to prevent the development of resistance.

For the prevention of Mycobacterium avium complex (MAC) in patients with advanced HIV infection, the recommended dose is 300 mg once daily.

For the treatment of disseminated MAC disease, the standard dose is 300 mg to 600 mg once daily, in combination with other antimycobacterial agents, such as a macrolide.

Adjust the dose when co-administered with potent CYP3A4 inhibitors (e.g., fluconazole, clarithromycin). A 50% dose reduction is often required to prevent toxicity and adverse effects like uveitis.

In patients with severe renal impairment (creatinine clearance less than 30 ml/min), reduce the total daily dose by 50%.

Take capsules with a full glass of water. To ensure optimal absorption, administer on an empty stomach, at least one hour before or two hours after meals. If gastrointestinal intolerance occurs, administration with a small, low-fat meal is acceptable, though this may slightly reduce bioavailability.

Do not crush or chew the capsules. Swallow them whole.

The total daily dose should not exceed 600 mg due to an increased risk of adverse reactions. Monitor liver function tests and complete blood counts periodically during long-term therapy.

Adverse Reactions

From the digestive system: nausea, vomiting, taste disturbance, dyspepsia, belching, flatulence, diarrhea, abdominal pain, increased activity of hepatic transaminases, alkaline phosphatase, jaundice, hepatitis, pseudomembranous colitis.

From the hematopoietic organs: leukopenia, including neutropenia, thrombocytopenia, anemia, hemolysis.

From the musculoskeletal system: arthralgia, myalgia, myositis.

From the nervous system: insomnia.

From the respiratory system: dyspnea.

From the immune system: fever, rash, eosinophilia, bronchospasm, anaphylactic shock, uveitis.

Other: asthenia, chest pain, fever, flu-like syndrome, orange discoloration of urine, skin discoloration.

Contraindications

Hypersensitivity to rifabutin and other rifamycins; pregnancy, breastfeeding period; children and adolescents under 18 years of age.

With caution severe renal failure, hepatic insufficiency, viral hepatitis, severe atherosclerosis.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy. If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindicated for use in hepatic insufficiency, viral hepatitis.

Use in Renal Impairment

Contraindicated for use in severe renal failure. With a creatinine clearance of less than 30 ml/min, a 50% dose reduction is indicated.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

To prevent the rapid development of resistance, Rifabutin is used simultaneously with macrolides; in AIDS patients with concomitant MAC infection – with clarithromycin; for the prevention of candidiasis – with antifungal agents. In these cases, the dose of rifabutin should be reduced.

During treatment with rifabutin, liver function and peripheral blood picture should be monitored.

Taking folic acid is effective for the prevention of anemia.

Rifabutin may impart a reddish-orange color to urine, skin, and secreted fluids. Patients taking Rifabutin should not wear contact lenses due to the possibility of them turning orange.

The use of rifabutin as monotherapy for the prevention of disease caused by Mycobacterium avium in tuberculosis patients may lead to the development of cross-resistance to rifabutin and rifampicin.

It is advisable to combine Rifabutin with antituberculosis drugs that do not belong to the rifamycin group.

When used concomitantly with rifabutin, oral contraceptives may be ineffective; other means of contraception should be used.

Effect on ability to drive vehicles and mechanisms

During the use of rifabutin, patients should exercise caution when driving vehicles and mechanisms, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Rifabutin is an inducer of liver microsomal enzymes, therefore it accelerates the metabolism and reduces the activity of glucocorticosteroids, oral hypoglycemic agents, indirect anticoagulants, oral contraceptives, digitalis preparations, beta-blockers, class I antiarrhythmic agents, calcium channel blockers.

With simultaneous use of rifabutin with zidovudine, a slight decrease in the concentration of the latter in blood plasma was noted, which has no clinical significance.

With simultaneous use of fluconazole and clarithromycin, the concentration of rifabutin in plasma increases.

With simultaneous use of rifabutin and zidovudine, the concentration of the latter in plasma decreases.

Combined use of Rifabutin with pyrazinamide, prothionamide and isoniazid is indicated due to pronounced synergy at the microbiological level.

Simultaneous use with fluoroquinolones is not recommended.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.