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

Pharmacodynamics:Semisynthetic broad-spectrum antibiotic, rifamycin derivative. Suppression of the synthesis of bacterial RNA by binding of the beta-subunit of DNA-dependent RNA polymerase, which prevents the enzyme from attaching to DNA, thus blocking the initiation of RNA transcription. Anti-tuberculosis drug I of the series.

Pharmacokinetics:

It is well absorbed from the digestive tract. It is distributed in most tissues and body fluids, excreted by breast milk. Being lipid soluble, it can act on intracellularly sensitive bacteria, including the Mycobacterium genus. VD 1.6 l / kg (in adults) and 1.1 l / kg (in children). The connection with plasma proteins is very high (89%). Biotransformation in the liver. T1 / 2 (abstention) ~ 0.6 h. T1 / 2 (elimination) 3-5 h (at the beginning of application), with repeated admission is reduced to 2-3 h. TCmax after oral administration 1.5-4 h, can slow down and decrease Cmax when taken with food. Cmax in adults with oral administration of 600 mg - 7-9 μg / ml; in children (6-58 months) with 10 mg / kg, mixed with apple juice or simple syrup, ~ 11 μg / ml. Cmax after iv introduction for 30 min: 600 mg in adults ~ 17.5 μg / ml; 300 mg / m2 in children (3 months to 12 years) ~ 26 μg / ml. Elimination with feces (60-65%, there is intestinal-hepatic recycling of rifampicin,but not its active metabolite); kidneys (6-15% as unchanged substance, 15% as active metabolite and 7% as inactive 3-formyl derivative). Does not accumulate if the kidney function is impaired; the rate of excretion rises during the first 6-10 days of therapy, possibly due to autoinduction of microsomal liver enzymes; when taking high doses, excretion may slow down due to saturation of the excretory pathway with bile. It is not removed during hemo- or peritoneal dialysis. According to preliminary data, when HIV is coinfected with mycobacteria (M. tuberculosis or M. avium), the pharmacokinetics change: in particular, malabsorption of rifampicin is often present, which can significantly affect the effectiveness of treatment.

Indications:Tuberculosis (including tuberculous meningitis) as part of combination therapy.
MAS infection.
Infectious-inflammatory diseases caused by susceptible to rifampicin pathogens (including osteomyelitis, pneumonia, pyelonephritis, leprosy, meningococcal carriage).

ICD-10

I.A15-A19.A16.8 Tuberculosis of other respiratory organs without mention of bacteriological or histological confirmation

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

I.A15-A19.A15.8 Tuberculosis of other respiratory organs, confirmed bacteriologically and histologically

I.A30-A49.A30 Leprosy [Hansen's disease]

I.A30-A49.A39 Meningococcal infection

X.J10-J18.J15 Bacterial pneumonia, not elsewhere classified

XIII.M86-M90.M86 Osteomyelitis

XIV.N10-N16.N10 Acute tubulointerstitial nephritis

XIV.N10-N16.N11 Chronic tubulointerstitial nephritis

Contraindications:Hypersensitivity.
Jaundice, recently transferred (<1 year) infectious hepatitis.
Chronic renal failure.
Severe pulmonary heart failure.
Lactation.

Carefully:

Alcoholism, a violation of the liver.

Pregnancy and lactation:

FDA recommendation category C.

Rifampicin penetrates the placenta and in rare cases causes postnatal bleeding in the mother and newborn during treatment in the last weeks of pregnancy; may require the appointment of vitamin K. A thorough examination of the newborn for side effects. Rifampicin excreted in breast milk. If necessary, use during lactation should stop breastfeeding.

Dosing and Administration:

When you receive inwards adults and children - 10 mg / kg 1 time / day or 15 mg / kg 2-3 times a week. Take on an empty stomach, the duration of treatment is set individually.

Intravenously adults - 600 mg 1 time / day or 10 mg / kg 2-3 times a week, children - 10-20 mg / kg 1 time / day or 2-3 times a week.

maybe introduction to the pathological focus (by inhalation, intracavitary administration, as well as the introduction of a skin lesion into the focus) for 125-250 mg.

Maximum doses: for adults, daily intake is 1.2 g, for children 600 mg, for intravenous administration for adults and children - 600 mg.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, decreased appetite; increased levels of hepatic transaminases, bilirubin in blood plasma, pseudomembranous colitis, hepatitis.

Allergic reactions: urticaria, angioedema, bronchospasm, flu-like syndrome.

On the part of the hematopoiesis system: rarely - thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, hemolytic anemia.

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

From the urinary system: necrosis of the kidney canals, interstitial nephritis, acute renal failure.

From the endocrine system: violation of the menstrual cycle.

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

Overdose:No data.

Interaction:

Aminophylline, oxtriphylline - acceleration due to their metabolism induction of hepatic microsomal enzymes and enhancing their clearance.

Amprenavir, indinavir, nelfinavir, ritonavir, saquinavir - acceleration of their metabolism with a decrease in their concentration in the blood plasma due to the induction of cytochrome P450 enzymes; In addition, antiretroviral drugs slow the metabolism of rifabutin with an increase in its concentration in the blood plasma; it may be necessary to adjust the dose of both agents.

General anesthetics, inhaled hydrocarbons except isoflurane - prolonged use of hepatic enzyme inducers to anesthesia accelerates the metabolism of anesthetics and increases the risk of hepatotoxicity.

Anticoagulants, derivatives of coumarin or indanedione - acceleration of their metabolism with a significant decrease in their effectiveness; MF may require monitoring at least 1 time per day and dose correction anticoagulant before and after treatment with rifampicin.

Barbiturates, β-adrenoblockers - accelerate the metabolism of these agents and reduce their effectiveness by inductionmicrosomal liver enzymes; a dose adjustment may be required.

Hepatotoxic agents [abacavir, aldesleukin, amiodarone, anabolic steroids, androgens, asparaginase, acetaminophen (with long-term high-dose therapy or acute overdose), acitretin, valproic acid, sodium valproate, retinol with chronic overdose, halothane, dantrolene, dapsone, daunorubicin, disulfiram, fat emulsions (with intravenous long-term use), iron preparations (with overdose), zidovudine, gold compounds, ACE inhibitors, HMG-CoA reductase inhibitors, imatinib, itraconazole, carbamazepine, carmustine, ketoconazole (ingestion), lamivudine, mercaptopurine, methotrexate, methyldopa, naltrexone (with prolonged use in high doses), nevirapine, a nicotinic acid (when used in high doses as a hypolipidemic agent in a sustained release dosage form), nilutamide, nitrofurans, NSAIDs, plikamycin, rosiglitazone, a combination of sulfamethoxazole and trimethoprim, sulfonamides (for systemic use), tizanidine, tolcapone, toremifene, tretinoin, phenothiazines, phenytoin, fluconazole, flutamide, cytarabine, epirubicin, erythromycin, estrogens, ethanol, ethionamide, etretinat] - increased hepatotoxicity of isoniazid; Combinations should be avoided.

Special instructions:

Rifampicin in monotherapy is not indicated for the treatment of meningococcal infections due to the possibility of rapid development of resistance.

The combination of rifampicin with pyrazinamide is generally not recommended for the treatment of latent tuberculosis, regardless of the presence of HIV co-infection, due to the high incidence of hepatotoxicity.

The maximum dose (for adults and children) is 600 mg / day.

To ensure optimal absorption, it is preferable to take rifampicin on an empty stomach (for> 1 h before or> 2 hours after ingestion), with enough water (240 ml). However, with the development of irritation of the gastrointestinal tract, it is possible to take the drug with food.

If the capsules are swallowed, their contents can be mixed with apple juice or jelly.

Intravenous infusion is performed under the control of blood pressure; with prolonged administration, it is possible to develop phlebitis.

Since monotherapy of tuberculosis with rifampicin may lead to rapid development of resistance, the drug should be administered only in combination with other anti-tuberculosis drugs.

Rifampicin is the main component of currently recommended tuberculosis therapy regimens. The effective regimen in HIV-infected patients includes rifampicin and isoniazid for ≥6 months, then pyrazinamide + ethambutol / streptomycin for the first 2 months. Adequate treatment of tuberculosis in HIV-infected patients is particularly relevant, since tuberculosis in this category of persons is potentially fatal, but treatment should be individualized and conducted with the advice of an expert with experience of therapy of this association. In addition, all HIV-infected patients are at risk of tuberculosis infection and should be carefully screened for the need for isoniazid preventive therapy regardless of the treatment with protease inhibitors.

Instructions

Rifampicin (Rifampicinum)