The mechanism of action is associated with inhibition of the synthesis of amino acids by inhibiting DNA-dependent RNA polymerase. Rifabutin is active against Mycobacterium tuberculosis, both sensitive and rifampicin resistant strains. Its activity against microorganisms resistant to rifampicin, due to its ability to inhibit thymidine incorporation into the DNA of sustanon 350 tuberculosis. In addition, rifabutin is active against non-tuberculous (atypical) bacteria, including Mycobacterium avium intracellular complex (MAC).
The spectrum of activity of rifabutin includes Gram-positive and Gram-negative bacteria.
Rifabutin is rapidly absorbed and the maximum plasma concentration of the drug (Cmax) is reached approximately 2-4 hours after ingestion. Plasma drug levels maintained above the minimum inhibitory concentration (MIC) for M. tuberculosis and 30 hours after admission. As was shown in healthy volunteers with single dose of 300, 450 and 600 mg of rifabutin pharmacokinetics is linear, while Cmax is determined in the range of 0.4-0.7 g / ml.
Rifabutin actively penetrate into the cells. The ratio of its intra- and extracellular concentrations ranged from 9 in neutrophils to 15 in human monocytes.
High intracellular levels are likely to have a key to maintaining the activity of rifabutin against intracellular pathogens such as mycobacteria. Rifabutin and its metabolites are excreted primarily by the kidneys. Among the 5 known main metabolites of rifabutin are 25-and 31-dezatsetilrifabutin gidroksirifabutin. First on the antibacterial activity comparable with rifabutin. The half-life of rifabutin is about 35-40 hours.
Sustanon 350 indicated for the treatment of infections caused by mycobacteria M. tuberculosis, MAC complex, as well as other atypical mycobacteria as M. xenopi (including 1The in immunocompromised patients). Mikobutin indicated for
- treatment of pulmonary tuberculosis: a new-onset, chronic and resistant;
- prophylaxis of infections caused by MAC complex in immunocompromised patients with the number of CD4 cells <200 .mu.l;
- treatment of disseminated M avium infection in patients with AIDS.
Mikobutin is contraindicated in patients with hypersensitivity to rifabutin or other rifamycin (eg, rifampicin) in history.
Due to lack of clinical experience in pregnant women, nursing mothers and children, Mikobutin should not be used in these patient groups.
Liver failure, kidney failure.
Dosing and Administration
Mikobutin administered orally once a day, regardless of meals.
- Pulmonary tuberculosis: 150 mg / day (1 capsule) for 6-9 months, or within 6 months after receipt of the negative results of the analysis. Patients chronically resistant tuberculosis increase the dose to 300-450 mg / day (2-3 capsules).
- Nontuberculous mycobacterial infection: 450-600 mg (3-4 capsules) up to 6 months after receiving a negative cultures. If Mikobutin used in combination with clarithromycin (eg., In the treatment of MAC), after the first month of treatment, the dose should be reduced to 300 mg (see. Section Special warnings and special precautions, and section Interactions with other drugs and other forms of interaction) .
- Prevention of MAC infection in immunocompromised patients: 300 mg (two capsules).
Dosage adjustment in the elderly is not required.
The most frequently occurring side effects, arranged by frequency in descending order, are related to:
- the gastrointestinal system, such as nausea, vomiting, increased liver enzymes, jaundice;
- Blood and lymphatic system, such as leucopenia, thrombocytopenia, and anemia;
- Musculoskeletal system: arthralgia and myalgia.
Also may experience fever, rash, and, rarely, other individual hypersensitivity reactions such as eosinophilia, bronchospasm, shock, reversible uveitis. We describe a limited number of cases, changes in skin color.
If overdose apply gastric lavage, symptomatic therapy is used and prescribed diuretics.
Interaction with other drugs and other forms of interaction
Treatment with rifabutin was accompanied by the induction of hepatic enzymes, belonging to the subfamily CYP450 FOR. The main metabolite of rifabutin (25 dezatsetilrifabutin; LM 565) also has this effect.The induction of metabolism influenced rifabutin can lower plasma levels of other drugs (which are metabolized by the action of isoenzymes CYP450 WA) was shown that the enzyme induction is completed within 5 days after treatment rifabutin and is independent of dose when used in the range of 300 to 600 mg. Drugs that competitively inhibit the activity of CYP450 FOR may increase circulating levels of rifabutin. Table. 1 summarizes the interaction of other drugs with rifabutin. The clinical significance of these interactions and the need for dose adjustment should be assessed taking into account the characteristics of the patient, severity of the disease, the spectrum of the drugs and the possible impact on the ratio of risk / benefit. Although rifabutin and rifampin have sustanon 350 similar structures, their physicochemical properties (in particular the degree of ionization and distribution coefficient) indicate significant differences in the distribution and the ability to induce isoenzymes CYP450. By inducing activity against enzymes is considerably inferior to rifampicin, rifabutin. Available evidence suggests that rifabutin inducing properties of 2-3 times weaker. Consequently, if the changes of circulating levels of the drug may affect the patient’s response to treatment, the clinical significance of possible interaction with rifabutin application should be lower than for rifampicin.