Farbutin^® (Capsules) Instructions for Use

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

ATC Code

J04AB04 (Rifabutin)

Active Substance

Rifabutin (Rec.INN registered by WHO)

Dosage Form

Farbutin®

Capsules 150 mg: 10, 30, 50, or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin size No. 0, brown in color; capsule contents – red-violet powder.

Excipients: microcrystalline cellulose – 117 mg, sodium lauryl sulfate – 7.5 mg, sodium carboxymethyl starch (sodium starch glycolate) – 3 mg, colloidal silicon dioxide (aerosil, grade A-300) – 6.25 mg, magnesium stearate – 6.25 mg.

Hard gelatin capsules size No. 0 (capsule body: iron oxide black – 0.39%, iron oxide red – 0.5%, titanium dioxide – 1%, iron oxide yellow – 0.27%, gelatin – up to 100%; capsule cap: iron oxide black – 0.39%, iron oxide red – 0.5%, titanium dioxide – 1%, iron oxide yellow – 0.27%, gelatin – up to 100%).

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the rifamycin group. Antituberculosis drug

Pharmacotherapeutic Group

Agents active against mycobacteria; antituberculosis agents; antibiotics

Pharmacological Action

Semi-synthetic 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 by inhibiting 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

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%. Penetrates the blood-brain barrier. T_1/2 – 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. Prevention 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 dosage regimen is set individually based on the indication and patient status.

For tuberculosis treatment, the typical adult dose is 150 mg to 300 mg once daily as part of a combination antituberculosis regimen.

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

For treatment of disseminated MAC disease, the dose is typically 300 mg to 600 mg once daily in combination with other antimycobacterial agents.

The maximum daily dose should not exceed 600 mg.

Adjust the dose when co-administered with strong CYP3A4 inhibitors such as fluconazole or clarithromycin; a 50% dose reduction is often required.

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

Take capsules with a full glass of water. Administer at the same time each day to maintain consistent plasma levels.

Swallow capsules whole; do not chew, crush, or open them.

Adverse Reactions

From the digestive system: nausea, vomiting, taste alteration, dyspepsia, belching, flatulence, diarrhea, abdominal pain, increased activity of liver 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 failure, viral hepatitis, severe atherosclerosis.

Use in Pregnancy and Lactation

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

Use in Hepatic Impairment

Contraindicated for use in hepatic failure, viral hepatitis.

Use in Renal Impairment

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

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Special Precautions

To prevent the rapid development of resistance, Rifabutin is used simultaneously with macrolides; in AIDS patients with associated 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.

Folic acid intake 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 not belonging to the rifamycin group.

With simultaneous use 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, protionamide, and isoniazid is indicated due to pronounced synergy at the microbiological level.

Simultaneous use of 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.