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

Pharmacodynamics:Semisynthetic broad-spectrum antibiotic, first-line anti-tuberculosis drug. At low concentrations, it has a bactericidal effect on Mycobacterium tuberculosis, Brucella spp., Chlamydia trachomatis, Legionella pneumophila, Rickettsia typhi, Mycobacterium leprae; in high concentrations - on some gram-negative microorganisms. Characterized by high activity against Staphylococcus spp. (including penicillinase-forming and many staffs of methicillin-resistant), Streptococcus spp., Clostridium spp., Bacillus anthracis; Gram-negative cocci: meningococci, gonococci. On gram positive bacteria ^^ act at high concentrations. It is active with respect to intracellular and extracellularly located microorganisms. Selectively inhibits the DNA-dependent RNA polymerase of sensitive microorganisms.When the drug is monotherapy, the selection of rifampicin-resistant bacteria is observed relatively quickly. Cross-resistance with other antibiotics (with the exception of the other rifamycins) does not develop.

Pharmacokinetics:

Absorption - fast, eating reduces the absorption of the drug. When administered on an empty stomach 600 mg, the maximum concentration in the blood - 10 μg / ml, the time to reach the maximum concentration in the blood - 2-3 hours. Communication with plasma proteins - 84-91%.

Quickly distributed to organs and tissues (the highest concentration in the liver and kidneys), penetrates into the bone tissue, the concentration in the saliva - 20% of the plasma. The apparent volume of distribution is 1.6 l / kg in adults and 1.1 l / kg in children.

Through the blood-brain barrier penetrates only in case of inflammation of the meninges. Penetrates through the placenta (plasma concentration of the fetus is 33% of the concentration in the mother's plasma) and excreted in breast milk (breastfeeding, children receive no more than 1% of the therapeutic dose of the drug).

Metabolized in the liver with the formation of pharmacologically active metabolite-25-O-deacetyltrifampicin. It is an autoinducer - it accelerates its metabolism in the liver, as a result of which the creatinine clearance is 6 l / h after the first dose, increases to 9 l / h after repeated administration.When ingestion is also possible, induction and enzymes of the intestinal wall.

The half-life of the drug (Tm) after ingestion is 300 mg - 2.5 h, 600 mg - 3-4 hours, 900 mg - 5 hours. After several days of repeated intake, the bioavailability decreases, and T1 / 2 after repeated administration of 600 mg is shortened to 1 - 2 hours

It is excreted mainly, with bile, 80% - in the form of a metabolite; kidneys - 20%. After taking 150-900 mg of the drug, the amount of rifampidine released by the kidney in unchanged form depends on the value of the dose taken and is 4-20%.

In patients with impaired excretory function of the kidneys, Tx is lengthened only in those cases when its doses exceed 600 mg. It is excreted in peritoneal dialysis and hemodialysis. In patients with impaired hepatic function, an increase in rifampicin plasma concentration and an elongation of T1 / 2 were noted.

Indications:

Tuberculosis of all forms and localizations in combination therapy.

Leprosy (in combination with dapsone and clofazimine - multibacillary types of the disease.

Infectious diseases caused by sensitive microorganisms (in cases of resistance to other antibiotics and in combination antimicrobial therapy, after excluding the diagnosis of tuberculosis and leprosy).

Brucellosis - as part of combination therapy with the antibiotic group of tetracyclines (doxycycline).

Meningococcal meningitis (prophylaxis in persons who were in close contact with meningococcal meningitis who fell ill, in Neisseria meningitidis bacilli carriers).

Contraindications:Hypersensitivity, jaundice, recently transferred (less than 1 year) infectious hepatitis, pregnancy (only for life indications), lactation period, chronic renal failure, pulmonary heart failure II-III st, breast age.

Dosing and Administration:

Inside, on an empty stomach, 30 minutes before meals. For the treatment of tuberculosis, at least one antituberculous agent is combined (isoniazid, pyrazinamide, ethambutol, streptomycin). Adults with a body weight of less than 50 kg - 450 mg / day; 50 kg and more - 600 mg / day. Children and newborns - 10-20 mg / kg per day; the maximum daily dose is 600 mg.

With tuberculous meningitis, disseminated tuberculosis, spinal cord injury with neurological manifestations, with the combination of tuberculosis with HIV infection, the total duration of treatment is 9 months, the drug is used daily, the first 2 months in combination with isoniazid, pyrazinamide and ethambutol (or streptomycin), 7 months - in combination with isoniazid.

In the case of pulmonary tuberculosis and detection of mycobacteria in sputum, the following 3 regimens are used (all with a duration of 6 months):

1. The first 2 months - as indicated above; 4 months - daily, in combination with isoniazid.

2. The first 2 months - as indicated above; 4 months - in combination with isoniazid, 2-3 times during each week.

3. Throughout the course - the reception in combination with isoniazid, pyrazinamide and ethambutol (or streptomycin) 3 times during each week. In cases where anti-TB drugs are used 2-3 times a week (as well as in case of exacerbation of the disease or inefficiency of therapy), they should be taken under the supervision of medical personnel.

For treatment of multibacillary types of leprosy (lepromatous, borderline, lepromatous and borderline) adults - 600 mg once a month in combination with dapsone (100 mg once a day) and clofazimine (50 mg once a day + 300 mg once a month ); Children -10 mg / kg once a month in combination with dapsone (1-2 mg / kg / day) and clofazimine (50 mg every other day + 200 mg once a month). The minimum duration of treatment is 2 years.

To treat multibacillary types of leprosy (tuberculoid and border tuberculoid) adults - 600 mg once a month,in combination with dapsone - 100 mg (1-2 mg / kg) once a day; Children - 10 mg / kg once a month, in combination with dapsone - 1-2 mg / kg / day. Duration of treatment - 6 months.

For the treatment of infectious diseases caused by sensitive microorganisms, it is prescribed in combination with other antimicrobial agents. The daily intake for adults is 0.6-1.2 g; for children and newborns - 10-20 mg / kg. Multiplicity of admission - 2 times a day.

For treatment of brucellosis - 900 mg / day once, in the morning on an empty stomach, in combination with doxycycline; average duration of treatment is 45 days:

For the prevention of meningococcal meningitis - 2 times a day every 12 hours for 2 days. Single doses for adults - 600 mg; for children -10 mg / kg; for newborns - 5 mg / kg.

Patients with impaired renal excretory function and preserved liver function need to adjust the dose only when it exceeds 600 mg / day.

Side effects:Nausea, vomiting, diarrhea, anorexia, erosive gastritis, pseudomembranous enterocolitis; increased activity of "hepatic" transaminases in the blood serum, hyperbilirubinemia; allergic reactions (urticaria, eosinophilia, Quincke's edema, and bronchospasm, arthralgia,fever); leukopenia, dysmenorrhea, headache, hepatitis; induction of porphyria; interstitial nephritis, decreased visual acuity, ataxia, disorientation, muscle weakness. With intermittent or irregular therapy or with the resumption of treatment after a break, flu-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.

Overdose:Symptoms: pulmonary edema, confusion, convulsions. Treatment: gastric lavage, the appointment of activated charcoal; symptomatic therapy, forced diuresis.

Interaction:Antacids, opiates, anticholinergics and ketoconazole reduce (in the case of simultaneous ingestion) bioavailability of rifampicin. Isoniazid and / or pyrazinamide increase the frequency and severity of liver function disorders to a greater extent than with the appointment of a single rifampicin, in patients with a previous liver disease. Preparations of PASC containing bentonite (aluminum hydrosilicate), should be prescribed not earlier than 4 hours after taking the drug, tk. absorption impairment is possible.Reduces the activity of oral anticoagulants, oral hypoglycemic drugs, hormonal contraceptives, digitalis preparations, antiarrhythmics (disopyramide, pirmenol, quinidine, mexiletine, tokainid), glucocorticosteroids, dapsone, hydantoins (phenytoin), hexobarbital, nortriptyline, benzodiazepines, sex hormones, theophylline, chloramphenicol, ketoconazole, itraconazole, cyclosporin A, azathioprine, beta adrenoblockers, slow calcium channel blancers, enalapril, cimetidine (rifampicin causes the induction of the enzyme system of the liver of the cytochrome P-450 system, accelerating the metabolism of drugs).

Special instructions:

During treatment the skin, mucus, sweat, feces, lacrimal fluid, urine becomes orange-red color. Can persistently stain soft contact lenses.

To prevent the development of microbial resistance, must be used in combination with others. Antimicrobials.

In the case of a flu-like syndrome, not complicated by thrombocytopenia, hemolytic anemia, bronchospasm, dyspnea, shock, and renal failure in patients receiving medication for intermittent scheme, you should consider switching to a daily intake.In these cases, the dose is increased slowly on the first day prescribe 75-150 mg, and the desired therapeutic dose is achieved in 3-4 days. In the event that the above serious complications are noted, rifampicin cancel.

It is necessary to monitor kidney function; possibly an additional appointment (especially in glucocorticosteroids.

Therapy during pregnancy (especially in I trimester) is possible only for health reasons. In the appointment of the last weeks of pregnancy may experience post-partum haemorrhage in the mother and the newborn bleeding. In this case, prescribe vitamin K.

Women of childbearing age during treatment should use reliable methods of contraception (oral hormonal contraceptives and additional non-hormonal methods of contraception).

In the case of prophylactic use, meningococcal bacilli carriers require strict monitoring of patients in order to timely identify the symptoms of the disease in the event of rifampicin resistance.

With prolonged use, a systematic control of the peripheral blood picture and liver function is shown.

During the treatment period, it is impossible to apply microbiological methods for determining the concentration of folic acid and vitamin B12 in the blood serum.

Form release / dosage:

Capsules 0,15 g.

Packaging:

Packing: 10 capsules per circuit pack; 20 or 30 capsules in cans of orange glass or cans of polymer or polymer bottles.

Each jar or bottle, or 2 contour mesh packages together with the instruction for use, is placed in a pack of cardboard.

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

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002210/07

Date of registration:15.08.2007

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp20.05.2016

Illustrated instructions

Instructions

Rifampicin (Rifampicin)