Rifampicin

General characteristics. Structure:

Active agent: 150 mg of rifampicin.

Excipients: ascorbic acid, sodium sulfite anhydrous.

Rifampicin — a semi-synthetic antibiotic of a wide range of antimicrobic action from group of Rifamycinums (ansamitsin).

Pharmacological properties:

Pharmacodynamics. Works bakteritsidno. Breaks synthesis of RNA in a bacterial cell, inhibiting RNA DNA-dependent - a polymerase. It is highly active concerning Mycobacterium tuberculosis, is an antituberculous remedy of the I row.

It is active concerning gram-positive bacteria (Staphylococcus spp, including polyresistant strains, Streptococcus spp., Bacillus anthracis, Clostridium spp.) and some gram-negative bacteria (Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Brucella spp., Legionella pneumophila). Rickettsia prowazekii, Mycobacterium leprae is active concerning Chlamydia trachomatis. He affects mushrooms. Rifampicin has virulitsidny effect on a rhabdovirus, suppresses development of rabichesky encephalitis.

Rifampicin resistance develops quickly. Cross stability with other antibacterial drugs (except for other rifampitsin) is not revealed.

Pharmacokinetics. The pharmacokinetics at adults and children is similar. Rifampicin is found in therapeutic concentration in pleural exudate, a phlegm, contents of cavities of a bone tissue; the greatest concentration is created in a liver and kidneys. Most untied fractions in not ionized look and freely extend in fabrics. Linkng with proteins of a blood plasma makes 80-90%.

Rifampicin gets through a blood-brain barrier, a placenta, it is found in breast milk. It Biotransformirutsya in a liver. The elimination half-life — about 3 hours, at a dose of 600 mg also increases till 5.1 o'clock, after a dose of 900 mg. At repeated, introduction the elimination half-life decreases and makes about 2-3 hours. In a dose to 600 mg/days with a renal failure of dose adjustment it is not required to patients. At in introduction therapeutic concentration of rifampicin remains during 8-12 h; concerning highly sensitive activators - during 24 h. It is brought out of an organism with bile, a stake and urine.

During this process rifampicin is exposed to an active dezatsetilirovaniye and almost all medicines as a part of bile are in such state about 6 hours. This metabolite keeps total antibacterial activity. The intestinal reabsorption decreases a dezatsetilirovaniye and removal is facilitated. To 30% of drug it is removed with urine.

Indications to use:

Medicine is shown to use for the patients who are not transferring oral therapy by drug (postoperative patients, a coma, absorption disturbance).

Tuberculosis: medicine is applied in combination with other antitubercular drugs. It is used for treatment of all forms of tuberculosis, including drug resistant. Drug is effective also against the majority of atypical strains of mycobacteria.

Leprosy: medicine is applied in combination with other protivoprokazny drugs.

Other infections: treatment of a brucellosis, disease of legionaries, serious staphylococcal infections. For prevention of emergence of resistant strains of microorganisms, reception of rifampicin needs to be combined with other antibacterial drugs.

Due to the bystry development of antibiotic resistance in the course of treatment, use of rifampicin at diseases of not tubercular etiology is limited to the cases which are not giving in to therapy by other antibiotics.

Route of administration and doses:

For preparation of solution part 0,15 g of rifampicin in 2,5 ml of sterile water for injections, vigorously stir up an ampoule with powder before full dissolution, the received solution dissolve 5% of solution of glucose in 125 ml. Enter intravenously with a speed of 60 — 80 thaws a minute.

At treatment of tuberculosis the daily dose for adults makes 0,45 g, at the severe fast-progressing forms — 0,6 g. The drug is administered 1 time a day within 1 month and more with the subsequent purpose of drug inside.

At infections of not tubercular nature intravenously enter the adult in a daily dose 0,3 — 0,9 g (2 — 3 introductions). Duration of treatment is defined individually depending on efficiency and portability of drug and can make 7 — 10 days. At emergence of an opportunity pass to administration of drug inside.

Features of use:

Monotherapy of tuberculosis rifampicin often is followed by development of resistance of the activator to an antibiotic therefore it should be combined with other antituberculous remedies. At treatment of not tuberculosis infections perhaps bystry development of resistance of microorganisms; this process can be prevented if to combine rifampicin with other chemotherapeutic means.

Administration of drug can be followed by urine coloring, a calla, saliva, sweat, the lacrimal liquid, contact lenses in red color. Intravenous infusion is carried out under control of the ABP.

Use during pregnancy and in the period of a lactation. Use of Rifampicin is contraindicated during pregnancy and in the period of a lactation. In the period of a lactation use of drug is possible only if the potential advantage for mother exceeds potential risk for the child.

Precautionary measures. With care apply at a pulmonary heart of the II-III degree, at the exhausted patients, at the patients abusing alcohol at a porphyria.

Treatment by rifampicin has to be carried out under careful medical observation. At long introduction development of phlebitis is possible. At development of thrombocytopenia, a purpura, hemolitic anemia, renal failure and other serious undesirable reactions administration of rifampicin is stopped. Precautionary measures have to be taken in case of a renal failure at a drug dose more than 600 mg/days.

At TB patients before an initiation of treatment it is necessary to check function of a liver. At adults: the following indicators have to be checked: liver enzymes, level of bilirubin, creatinine, general blood test and quantity of thrombocytes. At children to carry out basic tests there is no need, except for the explicit or clinically suspected serious condition of the patient. At patients with an abnormal liver function drug should be accepted only in case of need and under careful medical observation. At such persons it is necessary to adjust a drug dose and to control function of a liver, especially alaninaminotranspherase (ALT) and aspartate aminotransferase (ACT). Researches have to be conducted prior to therapy, weekly within 2 weeks, then every 2nd weeks in the next 6 weeks. At emergence of signs of an abnormal liver function drug has to be cancelled. It is necessary to consider to use other antitubercular drugs, after consultation of the specialist. If after normalization of function of a liver rifampicin reception was appointed again, it is necessary to control function of a liver daily. At patients with an abnormal liver function, at patients of advanced age, the exhausted patients and, perhaps, at children up to 2 years it is necessary to be careful at simultaneous use with an isoniazid (the risk of a hepatotoxic increases).

At some patients the hyperbilirubinemia can arise in the first days of treatment. Moderate increase in level of bilirubin and/or level of transaminases is not the indication for treatment interruption. It is necessary to control function of a liver and a clinical condition of the patient in dynamics. Rifampicin can lead to disturbance of a zhelchevydeleniye of the contrast means used for visualization of a gall bladder because of the competition for a zhelchevydeleniye. Thus, the research needs to be conducted before administration of drug.

Because of a possibility of immunological reaction, including an acute anaphylaxis, arising in connection with discontinuous therapy (from 2 to 3 weekly), patients have to be observed carefully and have to be informed on danger of discontinuous treatment.

At prolonged use of drug it is necessary to control a blood pattern in connection with a possibility of development of a leukopenia.

In case of preventive use for bacilli carriers of a meningokokk strict control of the state of health of patients is necessary timely to reveal disease symptoms in case of resistance to rifampicin. During treatment it is impossible to apply microbiological methods of definition of concentration of folic acid and B12 vitamin in blood serum. It is necessary to consider alternative methods of the analysis. Administration of drug can strengthen metabolism of endogenous substrates, including hormones of adrenal glands, hormones of a thyroid gland and vitamin D.

Rifampicin should not be applied intramusculary or subcutaneously. It is necessary to avoid hemorrhage during an injection; the local irritation and an inflammation because of infiltration can be observed.

If it occurred, it is necessary to make an injection in other place. Therapy during pregnancy (especially in the I trimester) is possible only according to vital indications. At purpose in recent weeks of pregnancy puerperal bleeding at mother and bleeding at the newborn can be observed. In this case appoint vitamin K. At researches on animals it was shown that rifampicin renders teratogenic effect. Drug gets through a placental barrier, however its impact on a human fruit is not known. Women of reproductive age during treatment should apply reliable methods of contraception (oral hormonal contraceptives and additional non-hormonal methods of contraception).

Influence on ability to control of motor transport and other potentially dangerous mechanisms: patients should abstain from all types of activity requiring special attention, bystry mental and motor reaction.

Side effects:

Drug, as a rule, is well transferred. Development of reactions of hypersensitivity, fever, сьшь on skin, nausea/vomiting is possible. Development of phlebitis and pain in the place of infusion is possible.

At discontinuous treatment the following side reactions are possible:

Skin reactions: a dermahemia, an itch, сьшь, a small tortoiseshell, it is rare - exfoliative dermatitis, pemfigoidny reactions, a multiformny erythema, Stephens-Johnson's syndrome, a Lyell's disease, a vasculitis.

Gastrointestinal reactions: anorexia, nausea, vomiting, discomfort in a stomach, diarrhea, pseudomembranous colitis. Development of hepatitis is possible (it is necessary to control function of a liver, watch the section "Precautionary measures").

Central nervous system: exceptional cases of psychoses.

Thrombocytopenia (with or without purpura), as a rule, arises at discontinuous therapy. Development of a hematencephalon is possible if treatment by rifampicin was continued after emergence of a purpura.

Exceptional cases of an intravascular blood coagulation, eosinophilia, leukopenia, hypostases, muscular weakness, myopathy, agranulocytosis, adrenal insufficiency at patients with insufficiency of function of adrenal glands are recorded.

At discontinuous treatment development is possible:

- "a grippopodobny syndrome": fever, a fever, a headache, dizziness, ostealgias develop most often within 3-6 months of therapy. Frequency of emergence of a syndrome changes, however this syndrome arises at 50% of the patients receiving drug once a week in a dose of 25 mg/kg and more,

- asthma and goose breathing,

- lowering of arterial pressure and shock,

- acute anaphylaxis,

- acute hemolitic anemia,

- the acute renal failure caused by an acute canalicular necrosis or acute intersticial nephrite.

If there are serious complications, for example, a renal failure, thrombocytopenia and hemolitic anemia, use of drug should be stopped.

Sometimes at prolonged treatment rifampicin at women recorded cases of disturbance of a menstrual cycle.

Rifampicin can lead to reddish coloring of urine, sweat, a phlegm and tear. The patient should be warned about it. Soft contact lenses can be also painted.

Interaction with other medicines:

Rifampicin - the strong inductor of R-450 cytochrome, can cause potentially dangerous medicinal interactions. Simultaneous use of rifampicin with other drugs which are also metabolized by R-450 cytochrome can accelerate their metabolism and decrease in action. In this case correction of a dose of these medicines can be required. Examples of the drugs which are metabolized R-450 cytochrome:

-   antiarrhytmic drugs (for example, Disopyramidum, мексилетин, quinidine, пропафенон, токаинид),

-   antiepileptic (for example, Phenytoinum),

-   antagonist of hormone (anti-estrogen, for example, Tamoxifenum, торемифен, гестинон),

-   neuroleptics (for example, haloperidol, арипипразол),

-   anticoagulants (for example, coumarins),

-   antifungal drugs (for example, флуконазол, итраконазол, кетоконазол, вориконазол),

-   antiviral drugs (for example, саквинавир, индинавир, эфавиренз, ампренавир, нелфинавир, атазанавир, лопинавир, not Virapinum),

-   barbiturates,

-   beta-blockers (for example, бисопролол, propranolol),

-   anxiolytics and hypnagogues (for example, diazepam, benzodiazepines, золпиколон, zolpidy),

-   blockers of calcium channels (for example, diltiazem, nifedipine, verapamil, нимодипин, исрадипин, никардипин, низолдипин),

-   antibacterial drugs (for example, chloramphenicol, кларитромицин, dapsone, doxycycline, ftorkhinolona, телитромицин),

-   corticosteroids,

-   cardiac glycosides (digitoxin, digoxin),

-   Clofibratum,

-   hormonal contraceptives,

-   estrogen,

-   drugs anti-diabetic (for example, Chlorproramidum, Tolbutamidum, sulphonylurea, розиглитазон),

-   immunodepressants (for example, cyclosporine, сиролимус, такролимус),

-   иринотекан,

-   hormone of a thyroid gland (for example, left thyroxine),

-   лозартан,

-   analgetics (for example, methadone, narcotic analgetics),

-   praziquantel, progestogens,

-   quinine,

-   riluzoly,

-   antagonists of 5-NTZ receptors (for example, ондансетрон),

-   the statines which are metabolized CYP3A4 (for example, симвастатин),

-   theophylline,

-   tricyclic antidepressants (for example, amitriptyline, нортриптилин),

-   cytotoxic drugs (for example, иматиниб),

-   diuretics (for example, эплеренон).

The patients accepting oral contraceptives should recommend to use alternative, non-hormonal methods of contraception.

At reception of rifampicin it becomes more difficult to control a condition of the patients suffering from a diabetes mellitus. If rifampicin is accepted along with a combination sakvinavir/ritonavir, the risk of a hepatotoxic increases. It is necessary to avoid such simultaneous use of medicines.

Simultaneous use of a ketokonazol and rifampicin leads to reduction of concentration of both drugs.

Parallel use of rifampicin and enalapril leads to decrease in concentration of enalaprilat, an active metabolite of enalapril. It is necessary to adjust a drug dosage.

Simultaneous use of antacids can reduce rifampicin absorption. Daily doses of rifampicin should be accepted, at least, in 1 hour prior to reception of antacids.

If drug is used along with a halothane or an isoniazid the risk of a hepatotoxic increases. It is necessary to avoid a concomitant use of rifampicin and a halothane. At the patients receiving at the same time rifampicin and an isoniazid it is necessary to monitor function of a liver carefully. P-aminosalicylic acid breaks rifampicin absorption. It is necessary to avoid combined use with HIV protease inhibitors (индинавир, нельфинавир).

Contraindications:

Hypersensitivity to rifampicin or other Rifamycinums, to any of excipients, jaundice (including mechanical), recently postponed (less than 1 year) infectious hepatitis, diseases of a liver and kidneys, pregnancy and a lactation (the refusal of breastfeeding is obligatory), a pulmonary heart, phlebitis.

At development of thrombocytopenia, a purpura, hemolitic anemia, an acute anaphylaxis, a renal failure and other serious undesirable reactions treatment by rifampicin is stopped. Use of drug is contraindicated at simultaneous introduction with a combination саквинавир / ритонавир.

Overdose:

Symptoms: nausea, vomiting, abdominal pains, an itch, a headache, the increased slackness, increase in activity of liver enzymes and/or bilirubin, brownish-red or orange coloring of skin, urine, sweat, saliva, tears, excrements (intensity of coloring is proportional to amount of the accepted rifampicin), at diseases of a liver can occur a loss of consciousness, in pediatric practice front or periorbital hypostasis is possible, development of hypotension, sinus tachycardia, ventricular arrhythmia, spasms, cardiac standstills and even death is possible.

The minimum acute or toxic dose is not established. However, not the deadly acute overdose at adults varies from 9 to 12 g of rifampicin. The deadly acute overdose at adults varies from 14 to 60 g. Some fatal cases of poisoning with rifampicin were connected with alcohol intake.

Not deadly overdose in pediatric practice aged from 1 up to 4 years of-100 mg/kg of body weight, 1-2 doses.

Treatment: Symptomatic therapy (there is no specific antidote): a gastric lavage, calling of vomiting, reception of absorbent carbon, at nausea and vomiting - antiemetic drugs, a hemodialysis, an artificial diuresis.

Storage conditions:

In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

In ampoules in packaging No. 10 or in bottles in packaging No. 1, No. 40.