Rifabutin - instructions for use, dose, side effects, contraindications

auxiliary substances: calcium hydrophosphate dihydrate - 83.0 mg, sodium lauryl sulfate - 2.2 mg, silicon dioxide colloid (aerosil) - 2.4 mg, magnesium stearate - 2.4 mg. capsules hard gelatinous 76.0 mg titanium dioxide E 171 0.33333% iron dye oxide red E 172 0.9300% iron dye oxide black E 172 0.5300% iron dye oxide yellow E 172 - 0.2000%, gelatin - up to 100%.

Description:Capsules № 1 brown: Contents of capsules - a powder of violet color with white impregnations.

Pharmacotherapeutic group:Antibiotic-rifamycin.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.04 Rifabutin

Pharmacodynamics:Semisynthetic broad-spectrum antibiotic. The mechanism of action is a selective inhibitor of DNA-dependent RNA polymerase; bactericidin.It is active against extracellular and intracellular microorganisms. Highly active against Mycobacterium spp. (M. tuberculosis, M. avium intracellulare complex (MAJ) and other atypical mycobacteria); many gram-positive and gram-negative bacteria. Rifabutin is active against 25-40% of M. tuberculosis, atypical mycobacteria resistant to rifampicin and other antibacterial drugs, which indicates an incomplete cross-resistance between these drugs. The rate of development of resistance to rifabutin is lower than to rifampicin. It is also active against many conditionally pathogenic microorganisms: Staphylococcus aureus is coagulase-negative, including methicillin-resistant ones; most types of streptococci (Streptococcus pneumoniae, including penicillin-resistant, S.viridans, S.pyogenes, moderately active against Enterococcus spp.). Gram-positive anaerobes are also sensitive to rifabutin: Bacillus anthracis, Clostridium spp., Including C. difficile; some pathogens of dangerous infectious diseases: Francisella tularensis, Brucella spp.

It is used in combination with other antibacterial drugs, in monotherapy - resistance develops rapidly. The activity of rifabutin in vivo in experimental tuberculosis is 10 times higher than that of rifampicin, which corresponds to the data in vitro.

Pharmacokinetics:Ingestion rifabutin quickly absorbed, the maximum concentration in the blood (Cmax) is reached after 2-4 hours, and the concentration in the blood serum, depending on the dose taken (300 mg and 600 mg) is 0.4 and 0.6 mg / l, respectively. The area under the rifabutin concentration curve depends on its dose and is significantly higher on day 1 of treatment than on day 28, due to the activation of metabolism. Taking the drug simultaneously with food reduces the rate of absorption, but its degree remains unchanged. The apparent volume of distribution is about 8-9 l / kg, the connection with blood proteins ranges from 70 to 94%. The concentration of rifabutin in tissues (in 5-12 hours after admission in a dose of 150-300 mg) is 8.5-10 times higher than in serum; However, the association of rifabutin with plasma proteins is not robust and does not prevent the accumulation of free rifabutin by the tissues. Due to its lipophilic properties rifabutin intensively accumulates and is permanently retained by all tissues of the body except for the brain. The concentration in the plasma is maintained above the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis up to 30 hours from the time of admission. It is well distributed in organs and tissues, penetrates into cells.It penetrates the blood-brain barrier (the concentration in the cerebrospinal fluid is about 50% of the concentration in the plasma). The highest concentration is in the lungs (24 hours after taking 5-10 times the plasma concentration). The content of rifabutin in leukocytes, lymphocytes and macrophages is 9-11 times higher than in the extracellular environment. The half-life of rifabutin (T1 / 2) ranges from 32 to 67 hours, which is 10 times more than rifampicin. After a single intake of rifabutin, the total amount of the withdrawn drug (rifabutin + inactive metabolites) in urine is 44% at 72 hours and 53% at 96 hours, in faeces at the same time intervals of 24 and 49%.

Indications:

- Chronic drug-resistant tuberculosis of the lungs, all forms and localization.

- First diagnosed drug-resistant tuberculosis of the lungs, all forms and localization.

- Mycobacteriosis caused by Mycobacterium avium intracellular complex (MAIC), Mycobacterium xenopiu.

- Prevention and treatment of MAIC infections in immunosuppressed patients (CD4 count of 200 / μl and below).

Rifabutin is prescribed in combination with other antituberculosis drugs.

Contraindications:Hypersensitivity to rifampines, pregnancy, lactation,children's age (due to the lack of clinical experience of the drug).

Carefully:With caution appoint rifabutin patients with severe atherosclerosis; liver diseases (including viral hepatitis B and C).

Pregnancy and lactation:Contraindicated for use during pregnancy (adequate and strictly controlled clinical studies of the safety of rifabutin during pregnancy have not been conducted). The drug is contraindicated for use in the lactation period (if you need to use the drug during lactation should stop breastfeeding).

Dosing and Administration:

Inside, 1 time per day, regardless of food intake. Prevention of infection in patients with immunosuppression - 300 mg / day.

In combination with other drugs: with non-tuberculous mycobacterial infection - 450-600 mg / day, up to 6 months from the time of receiving negative seeding. In chronic multidrug-resistant pulmonary tuberculosis - 300-450 mg / day, up to 6 months from the time of receiving negative seeding.

With newly diagnosed pulmonary tuberculosis - 150-300 mg / day, for 6 months.

When the creatinine clearance is below 30 ml / min, the dose is reduced by 50%.With moderate violations of the liver and / or kidneys do not require dose adjustment.

Side effects:

Nausea, vomiting, change in taste (dysgeusia), diarrhea, abdominal pain, increased activity of "liver" enzymes, jaundice.

Leukopenia, thrombocytopenia, anemia.

Arthralgia, myalgia.

Allergic reactions: fever, rash, rarely eosinophilia g, bronchoconstriction, anaphylactic shock, uveitis.

Overdose:Symptoms: increased side effects. Treatment: gastric lavage, symptomatic therapy, the appointment of diuretics.

Interaction:It induces cytochrome P450, accelerates the metabolism of drugs metabolized by this system. It is unlikely the development of clinically significant interactions with ethambutol, theophylline, sulfonamides, fluconazole, zalcitabine.

Fluconazole and clarithromycin increase the concentration of the drug in the plasma (with a simultaneous reception with clarithromycin, the daily dose is reduced to 150 mg). Rifabutin reduces the concentration of zidovudine in plasma.

Use of rifabutin in combination with pyrazinamide, isoniazid and prothionamide shown pronounced synergism due to microbiological level.It is not recommended simultaneous administration of fluoroquinolones.

PASC reduces the absorption of rifabutin. If it is necessary to use them together, the drugs are prescribed alternately (every other day).

Special instructions:

During the treatment period, it is necessary to periodically monitor the number of leukocytes, platelets in the peripheral blood, the activity of "liver" enzymes. The risk of uveitis increases with combination with clarithromycin or in high doses. With the development of uveitis, consultation of an ophthalmologist, temporary withdrawal of the drug is indicated.

May impart a reddish-orange color to urine, skin and decretible fluids. Patients taking the drug should not wear contact lenses because of the possibility of their coloring in orange. To prevent the development of anemia, folic acid is advisable. The use of rifabutin as a monotherapy for the prevention of M.avium disease in patients with tuberculosis can lead to the development of cross-resistance to rifabutin and rifampicin. It is advisable to combine with anti-tuberculosis drugs that do not belong to the rifamycin group.

Oral contraceptives may be ineffective, other contraceptive methods should be used.

Effect on the ability to drive transp. cf. and fur:Given the possible side effects, when taking the drug should be careful during work drivers of vehicles and people whose profession requires increased concentration and speed of psychomotor reactions.

Form release / dosage:

Capsules of 150 mg.

Packaging:

10 capsules in a contour cell box made of polyvinylchloride film and aluminum foil printed lacquered. 10 capsules in polymer cans complete with lids.

Each bank, 3 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002283

Date of registration:17.08.2011

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp03.05.2016

Illustrated instructions

Instructions

Rifabutin (Rifabutin)