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

Semisynthetic antibiotic of the rifamycin group. Has a wide range of action. The mechanism of action is probably related to inhibition of amino acid synthesis by inhibiting DNA-dependent RNA polymerase.

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

Rifabutin is also active against gram-positive bacteria: Staphylococcus spp. (including multidrug-resistant), 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).

Stability of strains of pathogens to rifabutin develops rapidly.

Pharmacokinetics:

It is well absorbed from the digestive tract (fatty food slows absorption, but does not affect its degree). Lipofilen, widely distributed in tissues, penetrates through the BBB, concentration in the CSF ~ 50% of that in blood plasma. VD 9.3 ± 1.5 l / kg. The highest concentration is in the lungs (24 hours after ingestion it is 5-10 times higher than the plasma one). Relationship with proteins 85% (high). Biotransformation in the liver with the formation of 5 inactive metabolites. It is the inducer of the isoenzymes CYP3A4, CYP3A5 and CYP3A7 in the liver. Half-life (terminal phase) 45 (16-69) h. TCmax 2-4 h. Cmax after a single dose of 300 mg - 375 ng / ml (in the dose range 300-600 mg the pharmacokinetics is linear). Concentration in plasma is maintained above the MIC for M. tuberculosis until 30 hours after administration. Elimination with feces (30%, 5% unchanged), kidneys (5% in the form of unchanged substance, 53% in the form of metabolites).

Indications:Prevention of infection caused by the complex Mycobacterium avium (MAC-infection), in persons with reduced immunity.
Treatment of secondary attached mycobacterial infection (including MAC infection).
Tuberculosis (as part of combination therapy).

ICD-10

I.A15-A19.A16 Tuberculosis of respiratory organs, not confirmed bacteriologically or histologically

I.A15-A19.A17.0 Tuberculous meningitis (G01 *)

I.A15-A19.A18 Tuberculosis of other organs

I.A30-A49.A31.0 Pulmonary infection caused by Mycobacterium

Contraindications:

Hypersensitivity to rifabutin, rifampicin or rifapentin.

Pregnancy, breast-feeding.

Carefully:

Renal failure, severe hepatic impairment.

Pregnancy and lactation:

Recommendations FDA category B.

Controlled studies in humans have not been conducted. In rats and rabbits, in doses ≤200 mg / kg (40 times higher than recommended for humans), it does not exhibit teratogenicity, but it reduces the viability of fetuses in rats at a dose of 200 mg / kg per day. At a dose of 40 mg / kg per day increases the frequency of skeletal development options in rats. Rabbits are toxic to the mother and increase the frequency of skeletal anomalies at a dose of 80 mg / kg per day. There is no information on the penetration into breast milk.

Dosing and Administration:

Inside adults and adolescents - 150-600 mg / day. Duration and frequency of reception are determined by the treatment regimen.

Side effects:

From the digestive system: nausea, vomiting, decreased appetite, diarrhea,pain in the epigastric region, erosive gastritis, pseudomembranous colitis; transient violations of the liver, hyperbilirubinemia, increased level of alkaline phosphatase, jaundice.

On the part of the hematopoiesis system: leukopenia, anemia, thrombocytopenia.

From the side of the central nervous system: headache, fatigue, ataxia.

From the musculoskeletal system: myalgia, arthralgia.

Allergic reactions: skin rash, itching.

From the side of the organ of vision: uveitis.

Other: red-brown staining of urine, feces, saliva, sputum, sweat, tears.

Overdose:Not studied.

Interaction:

Rifabutin is the inducer of microsomal liver enzymes, therefore accelerates metabolism and reduces the activity of SCS, hypoglycemic agents for oral administration, anticoagulants of indirect action, oral contraceptives, digitalis preparations, beta-blockers, class I antiarrhythmics, calcium channel blockers.

With the simultaneous use of rifabutin and zidovudine, there was a slight decrease in the concentration of the latter in blood plasma, which is not clinically significant.

Special instructions:

Rifabutin should not be used in monotherapy as a prophylaxis for the dissemination of Mycobacterium avium infection in patients with active tuberculosis due to the possibility of resistance1.

There is no information on the effectiveness of rifabutin in the prevention of tuberculosis. If it is necessary to prevent against M. tuberculosis and M. avium, a combination of isoniazid and rifabutin is also possible.

The daily dose of rifabutin 300 mg can be taken either during meals or independently, but with the development of nausea, vomiting, or other signs of irritation of the digestive tract, it may be useful to divide the daily dose in half into 2 divided doses and take with meals.

In severe renal failure (CK <30 ml / min), a reduction in the dose of rifabutin by 50% is necessary.

A change in the color of the tear fluid can lead to an irreversible change in the color of the contact lenses.

To facilitate the ingestion of capsules, their contents are recommended to mix with apple juice.

Antiretroviral agents significantly interact with rifamycins (rifampicin, rifabutin and rifapentin). Rifamycins accelerate the metabolism of antiretroviral agents, inducing cytochrome P450 oxidases, which can lead to a decrease in their concentration to a subtherapeutic level.In addition, antiretroviral agents slow the metabolism of rifamycins with an increase in their plasma concentration and the likelihood of toxic effects. Rifabutin to a lesser extent than rifampicin, induces cytochrome P450 enzymes and therefore can be combined with most antiretroviral agents. Inhibitors of reverse transcriptase (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir) are not metabolized by cytochrome P450 isoenzymes and therefore can be combined with rifamycins without dose adjustment.

Instructions

Rifabutin (Rifabutinum)