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Rifampicin

pharmachologic effect

Rifampin is a broad-spectrum antibiotic. It is active against mycobacteria tuberculosis and leprosy, acts on gram-positive (especially staphylococci) and gram-negative (meningococci, gonococci) cocci, and is less active against gram-negative bacteria.
Rifampin is well absorbed from the gastrointestinal tract. The maximum concentration in the blood is reached 2-2"/2 hours after oral administration.
When administered intravenously, the maximum concentration of rifampicin is observed at the end of the infusion (infusion). At the therapeutic level, the concentration of the drug when administered orally and intravenously is maintained for 8-12 hours, for highly sensitive pathogens - for 24 hours. Rifampicin penetrates well into the tissues and fluids of the body and is found in therapeutic concentrations in pleural exudate (accumulating between the membranes, protein-rich fluid surrounding the lungs), sputum, the contents of caverns (cavities in the lungs formed as a result of tissue necrosis), bone tissue. The highest concentration of the drug is created in the tissues of the liver and kidneys. It is excreted from the body with bile and urine.
Resistance to rifampicin develops rapidly. Cross-resistance with other antibiotics is not observed (with the exception of rifamiin).

Indications for use

The main indication for use is tuberculosis of the lungs and other organs.
In addition, the drug is used for various forms of leprosy and inflammatory diseases of the lungs and respiratory tract: bronchitis (inflammation of the bronchi), pneumonia (pneumonia) - caused by multiresistant (resistant to most antibiotics) staphylococci; with osteomyelitis (inflammation of the bone marrow and adjacent bone tissue); urinary and biliary tract infections; acute gonorrhea and other diseases caused by pathogens sensitive to rifampicin.
Due to the rapid development of microbial resistance, rifampicin is prescribed for non-tuberculosis diseases only in cases where other antibiotics are ineffective.
Rifampicin has a virulocidal (accompanied by complete or partial loss of biological activity of the virus) effect on the rabies virus, suppresses the development of rabies encephalitis (inflammation of the brain caused by the rabies virus); in this regard, it is used for the complex treatment of rabies in the incubation period (the period between the moment of infection and the appearance of the first signs of the disease).

Mode of application

Rifampin is taken orally on an empty stomach (2-1 hour before meals) or administered intravenously (adults only).
To prepare the solution, dilute 0.15 g of rifampicin in 2.5 ml of sterile water for injection, shake the ampoules with powder vigorously until completely dissolved, and dilute the resulting solution in 125 ml of 5% glucose solution. Inject at a rate of 60-80 drops per minute.
When treating tuberculosis, the average daily dose for adults is 0.45 g orally once a day. In patients (especially during an exacerbation) with a body weight above 50 kg, the daily dose can be increased to 0.6 g. The average daily dose for children over 3 years of age is 10 mg/kg (but not more than 0.45 g per day) 1 once a day. If rifampicin is poorly tolerated, the daily dose can be divided into 2 doses.
Intravenous administration of rifampicin is recommended for acutely progressive and widespread forms of destructive pulmonary tuberculosis (pulmonary tuberculosis that occurs with a violation of the structure of the lung tissue), severe purulent-septic processes (microbial contamination of the blood with subsequent formation of ulcers in the tissues), when it is necessary to quickly create a high concentration of the drug in the blood and if taking the drug orally is difficult or poorly tolerated by the patient.
When administered intravenously, the daily dose for adults is 0.45 g, for severe rapidly progressing (developing) forms - 0.6 g and is administered in 1 dose. The drug is administered intravenously for 1 month. or more, followed by a transition to oral administration, depending on the tolerability of the drug. The total duration of use of rifampicin for tuberculosis is determined by the effectiveness of treatment and can reach 1 year.
When treating tuberculosis with rifampicin (intravenously) in patients with diabetes mellitus, it is recommended to administer 2 units of insulin for every 4-5 g of glucose (solvent).
Monotherapy (treatment with one drug) of tuberculosis with rifampicin is often accompanied by the development of pathogen resistance to the antibiotic, so it should be combined with other antituberculosis drugs (streptomycin, isoniazid, ethambutol, etc., 770, 781), to which the sensitivity of Mycobacterium tuberculosis (the causative agent of tuberculosis) is preserved. . For leprosy, rifampicin is used according to the following regimens: a) a daily dose of 0.3-0.45 g is administered in 1 dose: if poorly tolerated, in 2 doses. Duration of treatment is 3-6 months, courses are repeated at intervals of 1 month; b) against the background of combination therapy, a daily dose of 0.45 g is prescribed in 2-3 doses for 2-3 weeks. at intervals of 2-3 months. for 1 year - 2 years or at the same dose 2-3 times every 1 week. within 6 months.
Treatment is carried out in combination with immunostimulating (increasing the body's defenses) agents.
For non-tuberculosis infections, adults take rifampicin orally at 0.45-0.9 g per day, and children - 8-10 mg/kg in 2-3 doses. Administered intravenously to adults in a daily dose of 0.3-0.9 g (2-3 injections). Administer over 7-10 days. As soon as the opportunity arises, switch to taking the drug orally.
For acute gonorrhea, it is prescribed orally at a dose of 0.9 g per day once or for 1-2 days.
To prevent rabies, adults are given 0.45-0.6 g per day orally; for severe injuries (bite to the face, head, hands) - 0.9 g per day; children under 12 years old - 8-10 mg/kg. The daily dose is divided into 2-3 doses. Duration of use: 5-7 days. Treatment is carried out simultaneously with active immunization (vaccinations).

Side effects

Treatment with rifampicin should be carried out under close medical supervision. Allergic reactions (of varying severity) are possible, although they are relatively rare; in addition, dyspeptic symptoms (digestive disorders), dysfunction (impaired function) of the liver and pancreas. With long-term use of the drug, it is necessary to periodically examine liver function and conduct blood tests (due to the possibility of developing leukopenia / decreased level of leukocytes in the blood /).
With rapid intravenous administration, blood pressure may decrease, and with prolonged administration, phlebitis (inflammation of the vein) may develop.
The drug reduces the activity of indirect anticoagulants (drugs that inhibit blood clotting), oral hypoglycemic drugs (drugs taken by mouth that lower blood sugar), and digitalis preparations. When taking anticoagulants and rifampicin simultaneously, the dose of anticoagulants should be reduced when the latter is discontinued.
The drug has a bright brown-red color. It colors (especially at the beginning of treatment) urine, sputum, and tear fluid an orange-reddish color.

Contraindications

Rifampicin is contraindicated in infants, pregnant women, jaundice, kidney disease with decreased excretory function, hepatitis (inflammation of liver tissue) and hypersensitivity to the drug. Intravenous administration is contraindicated in pulmonary heart failure (insufficient oxygen supply to body tissues due to heart and lung disease) and phlebitis.

Modern drugs: a complete practical guide. Moscow, 2000. S. A. Kryzhanovsky, M. B. Vititnova.

Attention!
Description of the drug " Rifampicin"on this page is a simplified and expanded version of the official instructions for use. Before purchasing or using the drug, you should consult your doctor and read the instructions approved by the manufacturer.
Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.

Gross formula

C 43 H 58 N 4 O 12

Pharmacological group of the substance Rifampicin

Nosological classification (ICD-10)

CAS code

13292-46-1

Characteristics of the substance Rifampicin

Semi-synthetic derivative of natural rifamycin. Crystalline powder of brick or brick-red color, odorless. Practically insoluble in water, sparingly soluble in formamide, slightly soluble in ethyl alcohol, soluble in ethyl acetate and methyl alcohol, readily soluble in chloroform. Sensitive to oxygen, light and air moisture.

Pharmacology

pharmachologic effect- bactericidal, anti-tuberculosis, broad-spectrum antibacterial, anti-leprosy.

It disrupts RNA synthesis in a bacterial cell: it binds to the beta subunit of DNA-dependent RNA polymerase, preventing it from joining DNA, and inhibits RNA transcription. Has no effect on human RNA polymerase. Effective against extra- and intracellular microorganisms, especially rapidly multiplying extracellular pathogens. There is evidence of blocking the last stage of poxvirus formation, possibly due to disruption of the formation of the outer shell. In low concentrations it acts on Mycobacterium tuberculosis, Brucella spp., Chlamidia trachomatis, Legionella pneumophila, Rickettsia typhi, Mycobacterium leprae, Staphylococcus aureus, incl. methicillin-resistant strains, Staphylococcus epidermidis, streptococci; in high concentrations - on some gram-negative microorganisms (Escherichia coli, Klebsiella, Proteus, Neisseria meningitidis, Neisseria gonorrhoeae, incl. beta-lactamase-forming). Active regarding Haemophilus influenzae(including those resistant to ampicillin and chloramphenicol), Haemophilus ducreyi, Bordetella pertussis, Bacillus anthracis, Listeria monocytogenes, Francisella tularensis, Clostridia difficile and other gram-positive anaerobes. Does not affect Mycobacterium fortuitum, family members Enterobacteraceae non-fermentative gram-negative bacteria (Pseudomonas spp., Acinetobacter spp., Stenothrophomonas spp.). In lesions it creates concentrations almost 100 times higher than the MIC for Mycobacterium tuberculosis(0.125-0.25 µg/ml). With monotherapy, pathogen resistance develops relatively quickly, due to a decrease in the penetration of rifampicin into the cell or a mutation of the DNA-dependent RNA polymerase. Cross-resistance with other antibiotics (except for the rifamycin group) is not observed.

Quickly and completely absorbed from the gastrointestinal tract; Eating food, especially one rich in fat, reduces absorption (by 30%). After absorption, it is quickly excreted in bile and undergoes enterohepatic recirculation. Bioavailability decreases with long-term treatment. Plasma protein binding - 84-91%. Cmax in the blood after oral administration of 600 mg of rifampicin is achieved after 2-2.5 hours and is 7-9 mcg/ml in adults, and 11 mcg/ml in children after taking a dose of 10 mg/kg. With intravenous administration, Cmax is reached by the end of the infusion and is 9-17.5 mcg/ml; The therapeutic concentration is maintained for 8-12 hours. The apparent volume of distribution in adults is 1.6 l/kg, in children - 1.2 l/kg. Most of the fraction of plasma not bound to proteins in non-ionized form penetrates well into tissues (including bone) and body fluids. Found in therapeutic concentrations in pleural and peritoneal exudate, cavity contents, sputum, saliva, nasal secretions; the highest concentration is created in the liver and kidneys. Penetrates well into cells. It passes through the BBB only in the case of inflammation of the meninges; in tuberculous meningitis, it is found in the cerebrospinal fluid in concentrations of 10-40% of those in the blood plasma. Metabolized in the liver to pharmacologically active 25-O-deacetylrifampicin and inactive metabolites (rifampinquinone, deacetylrifampinquinone and 3-formylrifampin). A strong inducer of microsomal enzymes of the cytochrome P450 system and intestinal wall enzymes. It has self-inductive properties, accelerates its biotransformation, as a result of which systemic clearance, after taking the first dose of 6 l/h, increases to 9 l/h after repeated dosing. T1/2 after oral administration of 300 mg is 2.5 hours; 600 mg - 3-4 hours, 900 mg - 5 hours; shortens with long-term use (600 mg - 1-2 hours). In patients with impaired renal excretory function, T1/2 is prolonged if the dose exceeds 600 mg; if liver function is impaired, there is an increase in plasma concentration and prolongation of T1/2. It is excreted from the body with bile in the form of metabolites (60-65%) and with urine, unchanged (6-15%), in the form of 25-O-deacetylrifampicin (15%) and in the form of 3-formylrifampin (7%). With increasing dose, the proportion of renal excretion increases. Small amounts of rifampicin are excreted in tears, sweat, saliva, sputum, and other fluids, turning them orange-red.

Rifampicin has been shown to be effective in the treatment of atypical mycobacteriosis, incl. in HIV-infected people, and for the prevention of infection caused by Haemophilus influenzae type b(Hib). There is evidence of a virucidal effect on the rabies virus and suppression of the development of rabies encephalitis.

Use of the substance Rifampicin

Tuberculosis (all forms) - as part of combination therapy. Leprosy (in combination with dapsone - multibacillary types of the disease). Infectious diseases caused by sensitive microorganisms (in case of resistance to other antibiotics and as part of combination antimicrobial therapy). Brucellosis - as part of combination therapy with a tetracycline antibiotic (doxycycline). Meningococcal meningitis (prevention in people who have been in close contact with patients with meningococcal meningitis; in bacilli carriers Neisseria meningitidis).

Contraindications

Hypersensitivity, incl. to other drugs of the rifamycin group, impaired liver and kidney function, infectious hepatitis suffered less than 1 year ago, jaundice, incl. mechanical.

IV administration: cardiopulmonary insufficiency of II-III degree, phlebitis, childhood.

Restrictions on use

Age under 1 year, alcoholism (risk of hepatotoxicity).

Use during pregnancy and breastfeeding

Contraindicated in the first trimester of pregnancy. In the second and third trimesters, it is possible only according to strict indications, after comparing the expected benefit to the mother and the potential risk to the fetus.

Rifampicin crosses the hematoplacental barrier (the concentration in the fetal blood serum at birth is 33% of the concentration in the maternal blood serum). Teratogenicity has been established in animal studies. In rabbits receiving doses up to 20 times higher than the usual daily dose for humans, osteogenesis disorders and toxic effects on the embryo were noted. Experiments on rodents showed that rifampicin in doses of 150-250 mg/kg/day caused congenital malformations, mainly cleft lip and palate, and spina bifida. When used in the last weeks of pregnancy, it may cause postpartum hemorrhage in the mother and bleeding in the newborn.

It is excreted in breast milk, with the child receiving less than 1% of the dose taken by the mother. Although no adverse reactions have been reported in humans, breastfeeding should be avoided during treatment.

Women of childbearing age need reliable contraception (including non-hormonal) during treatment.

Side effects of the substance Rifampicin

From the nervous system and sensory organs: headache, blurred vision, ataxia, disorientation.

From the cardiovascular system and blood (hematopoiesis, hemostasis): decreased blood pressure (with rapid intravenous administration), phlebitis (with long-term intravenous administration), thrombocytopenic purpura, thrombo- and leukopenia, bleeding, acute hemolytic anemia.

From the gastrointestinal tract: oral candidiasis, decreased appetite, nausea, vomiting, erosive gastritis, indigestion, abdominal pain, diarrhea, pseudomembranous colitis, increased levels of liver transaminases and bilirubin in the blood, jaundice (1-3%), hepatitis, damage to the pancreas.

From the genitourinary system: tubular necrosis, interstitial nephritis, acute renal failure, menstrual irregularities.

Allergic reactions: skin rash, itching, urticaria, fever, Quincke's edema, bronchospasm, lacrimation, eosinophilia.

Others: arthralgia, muscle weakness, herpes, induction of porphyria, influenza-like syndrome (with intermittent or irregular therapy).

Interaction

Being a strong inducer of cytochrome P450, it can cause potentially dangerous interactions.

Reduces the activity of indirect anticoagulants, corticosteroids, oral hypoglycemic agents, digitalis drugs, antiarrhythmic drugs (including disopyramide, quinidine, mexiletine), antiepileptic drugs, dapsone, methadone, hydantoins (phenytoin), hexobarbital, nortriptyline, haloperidol, benzodiazepines, drugs sex hormones, incl. oral contraceptives, thyroxine, theophylline, chloramphenicol, doxycycline, ketoconazole, itraconazole, terbinafine, cyclosporine A, azathioprine, beta-blockers, CCBs, fluvastatin, enalapril, cimetidine (due to the induction of microsomal liver enzymes and acceleration of the metabolism of these drugs). Should not be taken simultaneously with indinavir sulfate and nelfinavir, because their plasma concentrations are significantly reduced due to accelerated metabolism. PAS preparations containing bentonite (aluminum hydrosilicate) and antacids, when taken simultaneously, interfere with the absorption of rifampicin. When taken simultaneously with opiates, anticholinergics and ketoconazole, the bioavailability of rifampicin decreases; probenecid and co-trimoxazole increase its concentration in the blood. Concomitant use with isoniazid or pyrazinamide increases the incidence and severity of liver dysfunction (due to liver disease) and the likelihood of developing neutropenia.

Overdose

Symptoms: nausea, vomiting, abdominal pain, liver enlargement, jaundice, periorbital or facial swelling, pulmonary edema, blurred consciousness, convulsions, mental disorders, lethargy, “red man syndrome” (red-orange discoloration of the skin, mucous membranes and sclera).

Treatment: gastric lavage, activated charcoal, forced diuresis, symptomatic therapy.

Routes of administration

Inside, intravenously.

Precautions for the substance Rifampicin

For non-tuberculosis diseases, it is prescribed only when other antibiotics are ineffective (rapid development of resistance). Patients with impaired renal function require dose adjustment if it exceeds 600 mg/day. Use with caution in newborns, premature infants (due to age-related immaturity of liver enzyme systems) and in malnourished patients. Newborns should be prescribed simultaneously with vitamin K (prevention of bleeding). Use with caution in HIV-infected patients receiving HIV protease inhibitors. When administering rifampicin intravenously to patients with diabetes, it is recommended to administer 2 units of insulin for every 4-5 g of glucose (solvent). If a flu-like syndrome occurs with an intermittent dosing regimen, you should, if possible, switch to daily dosing; the dose is increased gradually. Whenever possible, you should switch from intravenous administration to oral administration (risk of phlebitis). During treatment, complete blood count, kidney and liver function should be monitored - first once every 2 weeks, then monthly; additional prescription or increase in the dose of glucocorticoids is possible. In case of prophylactic use in bacilli carriers Neisseria meningitidis Strict medical monitoring of the patient is necessary for timely detection of symptoms of the disease (if the pathogen develops resistance). PAS preparations containing bentonite (aluminum hydrosilicate) should be taken no earlier than 4 hours after taking rifampicin. During treatment, alcohol consumption should be avoided (the risk of hepatotoxicity increases).

active substance: rifampicin;

1 capsule contains 150 mg of rifampicin (based on 100% dry matter);

Excipients: Light magnesium carbonate, lactose monohydrate, calcium stearate.

The lid and body of the capsule contain dyes sunset yellow FCF (E 110), ponceau 4R (E 124) and titanium dioxide (E 171).

Dosage form. Capsules.

Basic physical and chemical properties: hard capsules with a cap and body of orange-red color, which contain powder or mass in the form of a partially or fully formed column from pale red to brownish-red with white inclusions.

Pharmacotherapeutic group. Antituberculosis drugs. Antibiotics.

ATX code

Pharmacological properties

Pharmacodynamics.

Rifampicin is a semisynthetic antibiotic of the rifamycin group, a first-line anti-tuberculosis drug. It has a bactericidal effect, the mechanism of which is due to the inhibition of the activity of DNA-dependent RNA polymerase by forming complexes with it, which leads to a decrease in the synthesis of RNA of microorganisms.

Rifampicin is a broad-spectrum antibiotic with the most pronounced activity against Mycobacterium tuberculosis.

The drug is active against atypical mycobacteria of various types (except M. fortuitum), gram-positive cocci (staphylococci, streptococci), anthrax bacilli, clostridia.

Gram-negative cocci - N. meningitidis And N.gonorrhoeae(including β-lactamase-forming) are sensitive, but quickly become resistant. Active regarding H. influenzae(including those resistant to ampicillin and chloramphenicol), H. ducreyi, B. pertussis, B. anthracis, L. monocytogenes, F. tularensis, Legionella pneumophila, Rickettsia prowazekii, Mycobacterium leprae. Rifampicin has a virucidal effect against the rabies virus and suppresses the development of rabies encephalitis.

Representatives of the family Enterobacteriaceae and non-fermentative gram-negative bacteria ( Pseudomonas spp., Acinetobacter spp., Stenothrohomonas spp. etc.) - insensitive. Does not affect anaerobic microorganisms and fungi.

Resistance to rifampicin develops rapidly. Cross-resistance to other anti-tuberculosis drugs (with the exception of other rifamycins) has not been detected.

Pharmacokinetics.

Rifampicin is well absorbed from the gastrointestinal tract, bioavailability when taken on an empty stomach is 95%. When taken with food, bioavailability is reduced. Creates effective concentrations in sputum, saliva, nasal secretions, lungs, pleural and peritoneal exudates, kidneys, and liver. Penetrates well into cells. Penetrates the blood-brain barrier; in tuberculous meningitis, it is found in the cerebrospinal fluid in effective concentrations. Penetrates the placenta and is found in breast milk. Binds to blood plasma proteins by 60-90%, dissolves in lipids. The maximum concentration in the blood is observed 2 hours after administration on an empty stomach, 4 hours after eating. The therapeutic concentration of the drug in the body is maintained

8-12 hours (for highly sensitive microorganisms – 24 hours). Rifampin can accumulate in the lung tissue and remain concentrated in the caverns for a long time. Metabolized in the liver to form an active metabolite. Half-life –

3-5 hours. It is excreted from the body mainly with bile and urine, and in small quantities with feces.

Clinical characteristics.

Indications

In complex therapy:

• tuberculosis of different localization, tuberculous meningitis, as well as atypical mycobacteriosis;
• infectious and inflammatory diseases of a non-tuberculous nature caused by pathogens sensitive to the drug (including severe forms of staphylococcal infection, leprosy, legionellosis, brucellosis);
• asymptomatic carriage N. meningitidis for the elimination of meningococci from the nasopharynx and the prevention of meningococcal meningitis.

Contraindications

• Hypersensitivity to rifampicin, other rifamycins or other components of the drug;
• severe dysfunction of the liver and kidneys;
• jaundice;
• recent (less than 1 year) infectious hepatitis;
• severe pulmonary heart failure;
• concomitant use of saquinavir/ritonavir.

Interaction with other drugs and other types of interactions.

Rifampicin is a potent inducer of liver microsomal enzymes (cytochrome P450) and may lead to potentially dangerous drug interactions. Concomitant use of rifampicin with drugs that are also metabolized by this enzyme system may accelerate the metabolism and reduce the activity of these drugs, therefore maintaining their optimal therapeutic concentration in the blood requires changing the dosage of these drugs when starting rifampicin use and after its discontinuation.

Rifampicin speeds up metabolism:

• antiarrhythmic drugs (for example, disopyramide, mexiletine, quinidine, propafenone, tocainide);
• beta blockers (eg, bisoprolol, propranolol);
• calcium channel blockers (eg, diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisolpidine);
• cardiac glycosides (digitoxin, digoxin);
• antiepileptic, anticonvulsant drugs (for example, phenytoin, carbamazepine);
• psychotropic drugs - antipsychotics (for example, haloperidol, aripiprazole), tricyclic antidepressants (for example, amitriptyline, nortriptyline), anxiolytics and hypnotics (for example, diazepam, benzodiazepines, zopiclone, zolpidem), barbiturates;
• antithrombotic agents (vitamin K antagonists), indirect anticoagulants: it is recommended to monitor the prothrombin time daily or as often as necessary to determine the required dose of the anticoagulant;
• antifungal drugs (eg, terbinafine, fluconazole, itraconazole, ketoconazole, voriconazole);
• antiviral drugs (eg, saquinavir, indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir, nevirapine);
• antibacterial drugs (eg, chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, telithromycin);
• corticosteroids (for systemic use);
• antiestrogens (for example, tamoxifen, toremifene, gestrinone), systemic hormonal contraceptives, estrogens, gestagens; For patients using oral contraceptives, alternative, non-hormonal methods of contraception should be recommended during rifampicin therapy;
• thyroid hormones (for example, levothyroxine);
• clofibrate;
• oral antidiabetic agents (sulfonylurea and its derivatives, for example, chlorpropamide, tolbutamide, thiazolidinediones);
• immunosuppressive drugs (eg, cyclosporine, sirolimus, tacrolimus);
• cytostatics (for example, imatinib, erlotinib, irinotecan);
• losartan;
• methadone, narcotic analgesics;
• praziquantel;
• quinine;
• riluzole;
• selective 5-HT 3 receptor antagonists (for example, ondansetron);
• statins that are metabolized by CYP 3A4 (eg, simvastatin);
• theophylline;
• diuretics (eg eplerenone).

Other interactions.

When combined with rifampicin:

• atovaquone - the concentration of atovaquone decreases and the concentration of rifampicin in the blood serum increases;
• ketoconazole - serum concentrations of both drugs decrease;
• enalapril - the concentration in the blood of enalaprilat, the active metabolite of enalapril, decreases. Depending on the clinical condition, dose adjustment of enalapril is possible;
• antacids - the absorption of rifampcin may be reduced. Rifampin should be taken at least 1 hour before taking antacids;
• probenecid and co-trimoxazole - an increase in the level of rifampicin in the blood;
• saquinavir/ritonavir - increases the risk of hepatotoxicity. This combination is contraindicated;
• sulfasalazine - the plasma concentration of sulfapyridine decreases, which may be the result of a disruption of the intestinal bacterial flora responsible for the conversion of sulfasalazine to sulfapyridine and mesalamine;
• halothane, isoniazid - increases the risk of hepatotoxicity. Concomitant use of rifampicin and halothane should be avoided. Patients receiving rifampicin and isoniazid should be closely monitored for liver function;
• pyrazinamide - severe liver injury, including death, has been reported in patients receiving rifampicin and pyrazinamide daily for 2 months; such a combination is possible only with careful monitoring and if the potential benefit outweighs the risk of hepatotoxicity and death;
• clozapine, flecainide - increases the toxic effect on the bone marrow;
• para-aminosalicylic acid preparations containing bentonite (aluminum hydrosilicate) - to ensure satisfactory concentrations of these drugs in the blood, the interval between their administration should be at least 4 hours;
• ciprofloxacin, clarithromycin - possible increase in the concentration of rifampicin in the blood; Cases of lupus-like syndrome have been reported when taken concomitantly with rifampicin.

Laboratory and diagnostic tests.

During treatment with rifampicin, the bromsulfalein test should not be used, since rifampicin changes the parameters of bromsulfalein excretion, which may lead to erroneous ideas about the violation of this indicator. Microbiological methods for determining the concentration of folic acid and vitamin B 12 in blood serum should also not be used.

Cross-reactivity and false-positive results are possible with opiate screening tests performed using the KIMS method, a quantitative immunoassay method; The use of reference tests (eg gas chromatography/mass spectrometry) is recommended.

Features of application

The use of rifampicin requires careful medical supervision.

Monotherapy with rifampicin for tuberculosis often leads to the development of resistant forms of mycobacteria. Therefore, rifampicin should be taken together with isoniazid, ethambutol, pyrazinamide and other anti-tuberculosis drugs.

It is advisable to use rifampicin in a daily rather than intermittent therapy regimen to reduce the risk of severe adverse reactions. Rifampicin is better tolerated when taken daily than when taken intermittently.

Before starting therapy, the level of liver enzymes, bilirubin, creatinine in the blood, the general blood picture, including the number of platelets, should be determined; with long-term use, periodic (preferably monthly) examination of blood composition and liver and kidney function is necessary.

In some patients, hyperbilirubinemia may occur in the first days of treatment as a result of competition between rifampicin and bilirubin for hepatic excretion.

In the event of the development of an influenza-like syndrome uncomplicated by thrombocytopenia, hemolytic anemia, bronchospasm, shortness of breath, shock and renal failure in patients treated with the drug according to an intermittent regimen, the possibility of switching to daily use should be considered. In these cases, the dose should be increased gradually: on the first day, 150 mg is prescribed, reaching the desired therapeutic dose in 3-4 days.

Rifampicin should be prescribed with extreme caution, only when absolutely necessary and under close medical supervision, to patients with liver disease. Severe hepatotoxicity, sometimes fatal, has been reported in patients with impaired liver function or in patients with normal liver function concomitantly taking other hepatotoxic drugs. In these patients, low doses of rifampicin and careful monitoring of liver function are recommended before starting treatment, weekly for the first two weeks, and every two weeks thereafter. If signs of hepatocellular damage appear, rifampicin should be discontinued immediately. Rifampicin therapy should also be discontinued if clinically significant changes in liver function occur.

When re-using rifampicin after normalization of liver function, it must be monitored daily.

Moderate liver dysfunction is usually transient and does not require discontinuation of the drug. It is possible to prescribe allochol, methionine, pyridoxine, vitamin B12.

When drinking alcohol during treatment and when used by patients with a history of alcoholism, the risk of hepatotoxicity increases.

If the treatment regimen is violated, an intentional or accidental interruption in taking the drug, or with an intermittent therapy regimen (less than 2-3 times a week), the risk of developing serious hypersensitivity reactions and other adverse reactions increases (anaphylactic shock, influenza-like syndrome, hemolytic anemia, acute renal failure, severe reactions from the skin, digestive system). Patients should be warned of the consequences of interrupting treatment.

When resuming treatment, you should consider switching to daily use of the drug, starting with a small dose (150 mg/day), gradually increasing it to the required therapeutic level. During this transition period, the functions of the renal and hematopoietic systems should be carefully monitored. The drug should be stopped immediately at the first manifestations of renal failure, thrombocytopenic purpura, or hemolytic anemia. Further use of the drug is contraindicated.

Treatment with antibacterial drugs, especially for severe diseases in the elderly, as well as in weakened patients and children, can lead to antibiotic-associated diarrhea, colitis, including pseudomembranous colitis. Therefore, if diarrhea occurs during or after treatment with rifampicin, it is necessary to exclude these diagnoses, including pseudomembranous colitis. In the absence of necessary treatment, toxic megacolon, peritonitis, and shock may develop.

Long-term use of antibacterial drugs can lead to excessive growth of insensitive microorganisms, fungi and the development of superinfection, requiring appropriate measures.

During treatment with rifampicin, women of reproductive age should use reliable methods of contraception, since taking rifampicin reduces the reliability of hormonal contraceptives (it is recommended to use additional non-hormonal contraceptives).

For gonorrhea, rifampicin, unlike penicillin, does not mask syphilis in mixed infections; serum tests for syphilis remain positive.

Rifampicin has the properties of an enzyme inducer (including delta-aminolevulinic acid synthetase), which can lead to increased metabolism of endogenous substrates, including adrenal hormones, thyroid hormones, vitamin D. There have been isolated reports of an association between exacerbations of porphyria and rifampicin therapy.

In some cases, there was a decrease in the level of circulating vitamin D metabolites, which was accompanied by a decrease in calcium and phosphate, as well as an increase in serum parathyroid hormone levels.

During treatment with rifampicin, the skin, sputum, sweat, feces, tears, and urine become orange-red. Permanent staining of soft contact lenses is possible.

During treatment you should not use:

• test with a load of bromsulfalein, since rifampicin competitively disrupts its excretion;
• microbiological methods for determining the concentration of folic acid and vitamin B 12 in blood serum;
• immunological methods, KIMS method when conducting screening tests for opiates.

The drug contains the excipient lactose monohydrate, so patients with rare hereditary forms of galactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome should not use this drug.

Use during pregnancy or breastfeeding.

Use during pregnancy is possible in exceptional cases for health reasons, if the expected benefit to the woman outweighs the potential risk to the fetus. Taking rifampicin in the last weeks of pregnancy increases the risk of bleeding in newborns and mothers in the postpartum period.

Rifampin passes into breast milk. If it is necessary to use the drug, breastfeeding should be discontinued.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

During treatment with rifampicin, you should refrain from driving vehicles or other mechanisms, given that during treatment there may be impaired coordination of movement, decreased concentration, and blurred vision.

Directions for use and doses

Rifampicin should be taken orally 30 minutes before or 2 hours after a meal, with a sufficient amount of water.

Tuberculosis:

adults prescribe at a dose of 8-12 mg/kg body weight per day. Patients weighing less than 50 kg - 450 mg/day, 50 kg and more - 600 mg/day;

children from 6 to 12 years old− 10-20 mg/kg body weight per day; the maximum daily dose should not exceed 600 mg.

The duration of anti-tuberculosis therapy is individual, determined by the therapeutic effect and can be 1 year or more. To avoid the development of mycobacterial resistance to rifampicin, the drug should be prescribed, as a rule, together with other first- and second-line anti-tuberculosis drugs in their usual doses.

Infectious and inflammatory diseases of non-tuberculosis nature caused by pathogens sensitive to the drug- brucellosis, legionellosis, severe forms of staphylococcal infection (together with another appropriate antibiotic to prevent the emergence of resistant strains):

adults prescribe 900-1200 mg per day in 2-3 doses, the maximum daily dose is 1200 mg. After the symptoms of the disease disappear, the drug should be taken for another 2-3 days.

Leprosy: the drug (in combination with immunostimulating agents) is prescribed orally at 600 mg per day in 1-2 doses for 3-6 months (repeated courses are possible with an interval of 1 month). According to another scheme (against the background of combined anti-leprosy therapy), the drug is prescribed in a daily dose of 450 mg, divided into 3 doses over 2-3 weeks with an interval

2-3 months for 1-2 years.

Carriage N. meningitidis: Rifampicin is prescribed for 4 days. Daily dose adults− 600 mg, children− 10-12 mg/kg body weight.

Liver dysfunction: the daily dose should not exceed 8 mg/kg for patients with impaired liver function.

Use in elderly patients: in elderly patients, the renal excretion of rifampicin decreases in proportion to the decrease in physiological renal function, and therefore the hepatic excretion of the drug increases compensatoryly. Caution should be exercised when prescribing rifampicin to patients of this age, especially if there are signs of liver dysfunction.

The drug in this dosage form should not be used by children under 6 years of age.

Overdose

Symptoms: nausea, vomiting, abdominal pain, headache, increased fatigue, increasing drowsiness, allergic reactions, increased body temperature, shortness of breath, fever, leukopenia, thrombocytopenia, acute hemolytic anemia, renal failure, skin reactions, itching, which may occur during short time after taking the drug.

Possible transient increases in the level of bilirubin, liver transaminases, enlarged liver, jaundice, loss of consciousness with serious liver dysfunction. A characteristic reddish tint to the skin, urine, sweat, saliva, tears and feces, the intensity of which is proportional to the amount of the drug taken.

There have been reports of facial or periorbital edema, usually in children.

Hypotension, sinus tachycardia, ventricular arrhythmia, seizures, and cardiac arrest have been reported in some fatal cases.

Treatment: discontinuation of the drug, gastric lavage during the first 2-3 hours, use of activated carbon, symptomatic therapy. In severe cases - forced diuresis, possibly hemodialysis, intensive supportive care and monitoring of hematological, renal, hepatic functions until the patient's condition is stabilized. There is no specific antidote.

Adverse reactions

Digestive tract. Nausea, vomiting, anorexia, diarrhea, heartburn, dyspepsia, discomfort, abdominal cramps/pain, flatulence, esophagitis, pseudomembranous enterocolitis, erosive gastritis, loss of appetite; with prolonged use, dysbacteriosis may develop.

Hepatobiliary system. Transient increases in liver transaminases, alkaline phosphatase, plasma bilirubin, jaundice with signs of hepatocellular damage, hepatitis, potentially fatal severe hepatotoxicity (eg, shock-like syndrome), usually in patients with impaired liver function or in patients with normal liver function who were simultaneously taking other hepatotoxic drugs. Baseline and further periodic liver function testing is recommended for all patients receiving long-term rifampicin therapy.

Hematopoietic system. Transient leukopenia, neutropenia, thrombocytopenia with or without purpura (more often with intermittent therapy with high doses or after restoration of interrupted therapy, with combined use with ethambutol), eosinophilia, decreased hemoglobin, hemolytic anemia, agranulocytosis, erythrocyte aplasia, methemoglobinemia, hemolysis, intravascular coagulation syndrome , hemorrhages. At the first manifestation of purpura, rifampicin therapy should be discontinued, as there have been reports of cerebral hemorrhage (including cerebral hemorrhage) and death when rifampicin therapy is continued or restarted after the development of purpura.

Nervous system. Headache, dizziness, paresthesia, weakness, asthenia, confusion, drowsiness, fatigue, ataxia, changes in behavior, decreased concentration, impaired coordination of movements, disorientation, myopathies, muscle weakness, pain in the extremities, generalized numbness.

Mental disorders. Psychoses.

The immune system. If the drug dosage regimen is violated or if treatment is resumed after a temporary break, with an intermittent treatment regimen, a flu-like syndrome is possible (petechiae, myalgia, arthralgia, episodes of fever, chills, nausea, vomiting, feeling of malaise). The development of dyspnea, bronchospasm, anaphylaxis reactions, including anaphylactic shock, other hypersensitivity reactions, including itching, urticaria, Quincke's edema, skin hyperemia, rash (including exanthema), pemphigoid reaction, exfoliative dermatitis has been reported , erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis (including leukocytoclastic), stomatitis, glossitis, conjunctivitis.

Urinary system. Impaired renal function (transient increases in blood urea nitrogen levels, hyperuricemia). Hemoglobinuria, hematuria, interstitial nephritis, glomerulonephritis, acute tubular necrosis, renal failure, including acute renal failure. These reactions may be a manifestation of hypersensitivity reactions, usually occur when taking the drug irregularly or when resuming treatment after a break, with an intermittent treatment regimen, and are usually reversible when rifampicin therapy is stopped and appropriate treatment is carried out.

Other. Decreased blood pressure (associated with hypersensitivity reactions), hot flashes, swelling of the face and extremities, adrenal insufficiency in patients with adrenal dysfunction, menstrual irregularities (breakthrough bleeding, spotting, amenorrhea, prolongation of the menstrual cycle), blurred vision, orange-red coloring of skin, urine, feces, saliva, sputum, sweat, mucus, induction of porphyria, exacerbation of gout, lacrimation, herpes, wheezing.

Best before date

Storage conditions

In original packaging at a temperature not exceeding 25 ºС.

Keep out of the reach of children.

Package

10 capsules in a blister, 2 blisters in a pack; 90 capsules per container, 1 container per pack; 1000 capsules per container.

Manufacturer

Public Joint Stock Company "Research and Production Center "Borshchagovsky Chemical and Pharmaceutical Plant".

The location of the manufacturer and its address of place of business.

Ukraine, 03134, Kyiv, st. Mira, 17.

Rifampicin disrupts the formation of RNA in a bacterial cell: it binds to DNA-dependent RNA polymerase (beta subunit), preventing it from joining DNA, and inhibits RNA transcription. Rifampicin does not affect human RNA polymerase. Rifampicin is effective against intra- and extracellular microorganisms, especially against extracellular pathogens that multiply rapidly. There is evidence that rifampicin blocks the last stage of poxvirus formation, most likely due to disturbances in the formation of the outer shell.

In low concentrations, rifampicin acts on Brucella spp., Mycobacterium tuberculosis, Legionella pneumophila, Chlamidia trachomatis, Mycobacterium leprae, Rickettsia typhi, Staphylococcus epidermidis, Staphylococcus aureus (including methicillin-resistant strains), streptococci; in high concentrations it acts on some gram-negative microorganisms (Klebsiella, Neisseria meningitidis, Escherichia coli, Proteus, Neisseria gonorrhoeae, including beta-lactamase-forming ones). Rifampicin is also active against Haemophilus influenzae (including those resistant to chloramphenicol and ampicillin), Bordetella pertussis, Clostridia difficile, Haemophilus ducreyi, Bacillus anthracis, Francisella tularensis, Listeria monocytogenes and other gram-positive anaerobes. Rifampicin has no effect on members of the family Enterobacteraceae, Mycobacterium fortuitum, non-fermenting gram-negative bacteria (Stenothrophomonas spp., Acinetobacter spp., Pseudomonas spp.). In lesions, rifampicin creates concentrations that are almost 100 times higher than the MIC for Mycobacterium tuberculosis (0.125–0.25 μg/ml).

Resistance of the pathogen to rifampicin develops relatively quickly during monotherapy, which is caused by a mutation of the DNA-dependent RNA polymerase or a decrease in the penetration of the drug into the cell. Cross-resistance with other antibiotics (except for drugs of the rifamycin group) has not been observed.

Rifampin is completely and quickly absorbed from the gastrointestinal tract; foods, especially those rich in fat, reduce the absorption of rifampicin by 30%. After absorption, rifampicin is rapidly excreted in the bile and undergoes enterohepatic recirculation. The bioavailability of rifampicin decreases with prolonged therapy. Rifampicin is 84–91% bound to plasma proteins. The maximum concentration of rifampicin in the blood when taken 600 mg orally is reached after 2–2.5 hours and is (in adults) 7–9 mcg/ml, in children when taken 10 mg/kg - 11 mcg/ml. When administered intravenously, the maximum concentration is reached at the end of the infusion and is equal to 9–17.5 mcg/ml; The therapeutic level of rifampicin in the blood lasts 8–12 hours. The apparent volume of distribution is 1.2 l/kg in children and 1.6 l/kg in adults. The main part of the rifampicin fraction, which is not bound to plasma proteins, penetrates well in non-ionized form into fluids and tissues (including bone) of the body. Rifampin is found in therapeutic concentrations in the contents of caverns, peritoneal and pleural exudate, sputum, nasal secretions, saliva; the highest concentrations are created in the kidneys and liver. Rifampicin penetrates well into cells. Rifampicin penetrates the blood-brain barrier only during inflammation of the meninges, during tuberculous meningitis and in the cerebrospinal fluid and is found in concentrations that are 10–40% of those in the blood plasma. Rifampicin is metabolized in the liver to inactive metabolites (deacetylrifampinquinone, rifampinquinone and 3-formylrifampin) and the pharmacologically active 25-O-deacetylrifampicin. Rifampicin is a strong inducer of intestinal wall enzymes and microsomal enzymes of the cytochrome P450 system. It has self-inductive properties, accelerates its biotransformation, as a result, systemic clearance when taking the first dose is 6 l/h, and when taken again it increases to 9 l/h. The half-life of rifampicin when taken 300 mg orally is 2.5 hours; 600 mg - 3–4 hours, 900 mg - 5 hours; with prolonged use it is shortened (600 mg - 1–2 hours). In patients with impaired renal excretory function, the half-life increases if the dose is more than 600 mg; in case of violations of the functional state of the liver, an increase in the content of rifampicin in plasma and an increase in the half-life are observed. Rifampicin is excreted from the body in the urine: in the form of 3-formylrifampin (7%), in the form of 25-O-deacetylrifampicin (15%), unchanged (6–15%) and with bile in the form of metabolites (60–65%) . With increasing dose, the proportion of renal excretion increases. Small amounts of rifampicin are excreted in sweat, tears, sputum, saliva and other fluids, turning them orange-red. Rifampicin has been shown to be effective in the treatment of atypical mycobacteriosis (including in HIV-infected patients) and for the prevention of infectious diseases caused by Haemophilus influenzae type b (Hib). There is information about the virucidal effect of rifampicin on the rabies virus and the suppression of the development of rabies encephalitis.

Indications

All forms of tuberculosis - as part of combination treatment; leprosy (together with dapsone - multibacillary types of the disease); brucellosis - as part of a combination treatment with tetracycline antibiotics (doxycycline); infectious diseases that are caused by sensitive microorganisms (if they are resistant to other antibiotics, as well as as part of combined antimicrobial treatment); meningococcal meningitis (prevention in people who have been in close contact with patients with meningococcal meningitis; in carriers of Neisseria meningitidis bacilli).

Method of administration of rifampicin and dose

Rifampicin is taken orally on an empty stomach (2 hours after a meal or 30–60 minutes before a meal), washed down with a full glass of water, and administered intravenously (the rate of administration is 60–80 drops per minute). The daily dose can be divided into 2 administrations/administrations if rifampicin is poorly tolerated. Tuberculosis: orally or intravenously (with further transition to oral administration): adults weighing 50 kg or more - 600 mg, less than 50 kg - 450 mg 1 time per day 3 times a week or daily; the maximum daily dose is 600 mg; children: the dose is determined depending on age and body weight, but not more than 450 mg/day. The duration of treatment is 6–9–12 months or more. Leprosy: orally, adults - 600 mg, children - 10 mg/kg once a month, along with clofazimine and dapsone, for 2 years or more. Brucellosis: orally, adults - 900 mg/day for 45 days (together with doxycycline). Prevention of meningococcal meningitis: orally, every 12 hours, adults - 600 mg, children - a single dose of 10 mg/kg, newborns - 5 mg/kg for 2 days. Other infections: orally, adults - 450-900 mg/day, children - 8-10 mg/kg/day in 2-3 doses; intravenously for 7–10 days 300–900 mg/day.

For non-tuberculosis diseases, rifampicin is used only when other antibiotics are ineffective (due to the rapid development of resistance). Patients with impaired renal function require dose adjustments if they exceed 600 mg/day. Rifampicin is used with caution in premature and newborn infants (due to age-related immaturity of liver enzyme systems), as well as in malnourished patients. Newborns should be given rifampicin along with vitamin K to prevent bleeding. Rifampicin should be used with caution in HIV-infected patients receiving HIV protease inhibitors. When administering rifampicin intravenously to patients with diabetes, it is recommended to administer 2 units of insulin for every 4–5 g of glucose (solvent). If a flu-like syndrome develops during an intermittent dosing regimen, it is necessary, if possible, to switch to taking the drug every day; in this case, the dose must be increased gradually. When the opportunity arises, it is necessary to switch from intravenous administration to oral administration (due to the risk of developing phlebitis). During rifampicin therapy, it is necessary to monitor a general blood count, the functional state of the liver and kidneys - initially once every 2 weeks, then every month; additional prescription or increase in the dose of glucocorticoids is possible. When used prophylactically in carriers of the Neisseria meningitidis bacilli, strict medical monitoring of the patient is necessary for timely detection of symptoms of the disease (if the pathogen develops resistance). During rifampicin therapy, alcohol consumption should be avoided (the risk of hepatotoxicity increases). PAS preparations and products containing bentonite should be taken no earlier than 4 hours after taking rifampicin. To prepare a solution for intravenous administration, every 0.15 g of rifampicin is dissolved in 2.5 ml of water for injection, shaken well until completely dissolved and then mixed with 125 ml of a 5% glucose solution. Continuous use of rifampicin is better tolerated than intermittent use (2-3 times a week). When used in patients who are unable to swallow the entire capsule, as well as in children, the contents of the capsule can be mixed with apple jelly or puree. Rifampicin turns stool, urine, sputum, sweat, tears, nasal secretions, and skin orange-red. Rifampin can also permanently stain soft contact lenses. During treatment, it is not recommended to use microbiological methods for determining the content of vitamin B12 and folic acid in blood serum.

Contraindications for use

Hypersensitivity (including to other drugs of the rifamycin group), impaired functional state of the kidneys and liver, jaundice (including mechanical), infectious hepatitis, which was suffered less than 1 year ago; for intravenous administration: phlebitis, cardiopulmonary failure of 2 - 3 degrees, children's age.

Restrictions on use

Alcoholism, age under 1 year.

Use during pregnancy and breastfeeding

Taking rifampicin is contraindicated in the 1st trimester of pregnancy. Taking rifampicin in the 2nd and 3rd trimesters of pregnancy is possible only under strict indications and only after comparing the expected benefit to the mother and the possible risk to the fetus. Rifampin crosses the placental barrier. Rifampicin has been shown to be teratogenic in animal studies. In rabbits that received doses up to 20 times higher than the MRDC, toxic effects on the embryo and osteogenesis disorders were noted. In rodent studies, 150–250 mg/kg/day rifampicin was found to cause congenital malformations, mainly cleft palate and upper lip, and spina bifida. When rifampicin is used in the last weeks of pregnancy, bleeding in the newborn and postpartum hemorrhage in the mother may occur. Rifampin is excreted in breast milk. Although no adverse reactions have been reported in humans, breastfeeding should be avoided during rifampicin therapy. Women of childbearing age must use reliable contraception (including non-hormonal) during treatment.

Side effects of rifampicin

Sense organs and nervous system: ataxia, headache, disorientation, visual impairment; blood and circulatory system: decreased blood pressure (with rapid intravenous administration), phlebitis (with prolonged intravenous administration), thrombo- and leukopenia, thrombocytopenic purpura, acute hemolytic anemia, bleeding;
digestive system: oral candidiasis, decreased appetite, nausea, erosive gastritis, vomiting, digestive disorders, diarrhea, abdominal pain, pseudomembranous colitis, jaundice, increased levels of liver transaminases and bilirubin in the blood, damage to the pancreas, hepatitis;
genitourinary system: acute renal failure, interstitial nephritis, tubular necrosis, menstrual irregularities;
allergic reactions: itching, skin rash, urticaria, Quincke's edema, fever, lacrimation, bronchospasm, eosinophilia;
others: muscle weakness, arthralgia, induction of porphyria, herpes, influenza-like syndrome (with irregular or intermittent treatment).

Interaction of rifampicin with other substances

Since rifampicin is a potent inducer of cytochrome P450, potentially dangerous interactions may develop. Rifampicin reduces the activity of corticosteroids, indirect anticoagulants, oral hypoglycemic drugs, antiepileptic drugs, antiarrhythmic drugs (including disopyramide, quinidine, mexiletine), digitalis drugs, dapsone, hydantoins (phenytoin), methadone, hexobarbital, benzodiazepines, haloperidol, nortriptyline, sex hormone drugs ov (including oral contraceptives), theophylline, thyroxine, chloramphenicol, ketoconazole, doxycycline, itraconazole, cyclosporine A, terbinafine, azathioprine, calcium channel blockers, beta-blockers, fluvastatin, cimetidine, enalapril (due to induction of hepatic microsomal enzymes and acceleration of metabolism of these drugs). Do not take rifampicin together with nelfinavir and indinavir sulfate because their plasma concentrations are significantly reduced due to accelerated metabolism. Antacids, PAS preparations containing bentonite, when taken together with rifampicin, interfere with its absorption. When rifampicin is used concomitantly with opiates, ketoconazole and anticholinergics, the bioavailability of rifampicin is reduced; Co-trimoxazole and probenecid increase the concentration of rifampicin in the blood. The combined use of rifampicin with pyrazinamide or isoniazid increases the severity and incidence of liver dysfunction (in liver disease), as well as the possibility of developing neutropenia.

Overdose

In case of an overdose of rifampicin, nausea, abdominal pain, vomiting, jaundice, enlarged liver, swelling of the face or periorbital edema, pulmonary edema, convulsions, confusion, lethargy, mental disorders, “red man syndrome” (red-orange coloring of the mucous membranes, skin and sclera). Necessary: ​​gastric lavage, intake of activated carbon, forced diuresis and symptomatic treatment.

Tradename

Rifampicin

International nonproprietary name

Rifampicin

Dosage form

Capsules, 300 mg

Compound

One capsule contains

active substance- rifampicin 300 mg,

Excipients: lactose monohydrate, petroleum jelly (liquid paraffin), potato starch, sodium lauryl sulfate, colloidal anhydrous silicon dioxide (Aerosil), talc, magnesium stearate.

capsule shell: gelatin, titanium dioxide (E 171), azorubine (E 122).

Description

Hard gelatin capsules with a red body and cap.

The contents of the capsules are red-brown or brick-red powder or granules.

Pharmacotherapeutic group

Anti-tuberculosis drugs. Antibacterial drugs. Rifampicin.

ATX code J04AB02

Pharmacological properties

Pharmacokinetics

Rifampicin is well absorbed from the gastrointestinal tract. When taken, the maximum concentration of the drug in plasma is achieved after 2-4 hours and remains at a detectable level for up to 8 hours. However, in the blood and tissues, effective concentrations can persist for 12-24 hours. Plasma protein binding is 80-90%. The half-life is 2-5 hours. Rifampicin is metabolized in the liver. Rifampicin penetrates well into tissues and body fluids and is found in therapeutic concentrations in pleural exudate, sputum, cavity contents, and bone tissue. The highest concentration of the drug is created in the tissues of the liver and kidneys. It is excreted from the body with bile and urine.

Pharmacodynamics

Rifampicin is a semisynthetic broad-spectrum antibiotic from the rifamycin group. Inhibits the synthesis of ribonucleic acid (RNA).

It has a bacteriostatic and, in high concentrations, a bactericidal effect. Highly active against M. tuberculosis, it is a first-line anti-tuberculosis drug. Active against Escherichia coli, Pseudomonas, Indole-positive and Indole-negative, Proteus, Klebsiella, Staphilococcus aureus, Coagulase - negative staphylococci, Neisseria meningitides, Haemophilus influenzae, Legionella species, M.tuberculosis, M.kansassi, M.scrofulaceum, M .intracellulare and M.avium.

Indications for use

Tuberculosis of the lungs and other organs (all forms) as part of complex therapy.

Directions for use and doses

Rifampin is taken orally on an empty stomach (1/2-1 hour before meals).

When treating tuberculosis in adults: daily therapy (once a day) or intermittent therapy (3 times a week)

The maximum daily dose should not exceed 750 mg.

With insufficient liver function the daily dose should not exceed 8 mg/kg.

Use in elderly patients: In elderly patients, renal excretion of rifampicin decreases in proportion to the decline in physiological renal function, but due to a compensatory increase in liver excretion, the half-life of the drug is the same as in younger patients. However, caution should be exercised when using the drug in such patients, especially if there is evidence of liver dysfunction.

The duration of the course is 6-9-12 months or more. The duration of treatment is determined individually. If rifampicin is poorly tolerated, the daily dose can be divided into 2 doses.

Use as directed by a doctor.

Side effects

• skin hyperemia, itching, rash, urticaria, exfoliative dermatitis, pemphigoid reactions, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome, vasculitis
• loss of appetite, anorexia, erosive gastritis, heartburn, nausea, vomiting, flatulence, epigastric pain, abdominal discomfort, intestinal colic, diarrhea, pseudomembranous colitis, constipation
• visual impairment
• hepatitis, jaundice
• exacerbation of gout (increased serum uric acid)
• fatigue, drowsiness, rare cases of psychosis, depression
• Thrombocytopenia (with or without purpura) usually occurs with intermittent therapy. Possible fatal cerebral hemorrhage if treatment with rifampicin is continued after the onset of purpura
• rare cases of intravascular coagulation, eosinophilia, leukopenia, edema, muscle weakness, myopathy, agranulocytosis, adrenal insufficiency in patients with adrenal insufficiency, dysuria
• gynecomastia in patients with diabetes mellitus
• rarely possible dysmenorrhea, induction of porphyria
• Herpes is extremely rare

With intermittent treatment, the following may develop:

• “flu-like syndrome”: fever, chills, headache, dizziness, bone pain appear most often within 3-6 months of therapy. The incidence of the syndrome varies, but this syndrome occurs in 50% of patients receiving the drug once a week, at a dose of 25 mg/kg or more
• shortness of breath and wheezing
• decreased blood pressure and shock
• anaphylactic shock
• acute hemolytic anemia
• acute renal failure caused by acute tubular necrosis or acute interstitial nephritis, hematuria

If serious complications occur, such as renal failure, thrombocytopenia and hemolytic anemia, the drug should be discontinued.

With long-term treatment with rifampicin, women may experience menstrual irregularities.

Rifampin may cause a reddish coloration of the skin, urine, stool, sweat, sputum, and tears. Soft contact lenses can also stain.

Contraindications

• hypersensitivity to the components of the drug
• visual impairment (diabetic retinopathy, optic nerve damage)
• epilepsy, tendency to seizures
• history of poliomyelitis
• history of infectious hepatitis, jaundice
• thrombophlebitis
• severe atherosclerosis
• liver dysfunction
• renal dysfunction
• pregnancy, lactation period
• children under 18 years of age
• simultaneous use with saquinavir/ritonavir drugs

Drug interactions

Rifampicin is a strong cytochrome P-450 inducer and may cause potentially dangerous drug interactions. Concomitant use of rifampicin with other drugs that are also metabolized by cytochrome P-450 may accelerate their metabolism and decrease their effect. In this case, the dose of these medications may need to be adjusted. Examples of drugs metabolized by cytochrome P-450:

• antiarrhythmic drugs (eg, disopyramide, mexiletine, quinidine, propafenone, tocainide)
• antiepileptics (eg, phenytoin)
• hormone antagonist (antiestrogens, e.g. tamoxifen, toremifene, gestinone)
• antipsychotics (eg, haloperidol, aripiprazole)
• anticoagulants (eg, coumarins)
• antifungals (eg, fluconazole, itraconazole, ketoconazole, voriconazole)
• antivirals (eg, saquinavir, indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir, nevirapine)
• barbiturates (phenobarbital)
• beta blockers (eg, bisoprolol, propranolol)
• anxiolytics and hypnotics (eg, diazepam, benzodiazepines, zolpicolone, zolpidem)
• calcium channel blockers (eg, diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisoldipine)
• antibacterial drugs (for example, chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, telithromycin),
• corticosteroids
• cardiac glycosides (digitoxin, digoxin)
• clofibrate
• hormonal contraceptives
• estrogens
• antidiabetic drugs (eg, chlorpropamide, tolbutamide, sulfonylurea, rosiglitazone)
• immunosuppressants (eg, cyclosporine, sirolimus, tacrolimus)
• irinotecan
• thyroid hormone (eg, levothyroxine)
• losartan
• analgesics (eg, methadone, narcotic analgesics)
• praziquantel
• progestogens
• quinine
• riluzole
• 5-NT3 receptor antagonists (eg, ondansetron)
• statins metabolized by CYP3A4 (eg, simvastatin)
• theophylline
• tricyclic antidepressants (eg, amitriptyline, nortriptyline)
• cytotoxic drugs (eg, imatinib)
• diuretics (eg, eplerenone)

Patients taking oral contraceptives should be advised to use alternative, non-hormonal methods of contraception.

When taking rifampicin, it becomes more difficult to control the condition of patients with diabetes.

If rifampicin is taken concomitantly with saquinavir/ritonavir combination, the risk of hepatotoxicity is increased. Concomitant use of rifampicin with saquinavir/ritonavir is contraindicated.

The simultaneous use of ketoconazole and rifampicin leads to a decrease in the concentrations of both drugs.

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

Concomitant use of antacids may reduce the absorption of rifampicin. Daily doses of rifampicin should be taken at least 1 hour before taking antacids.

If the drug is used simultaneously with halothane or isoniazid, the risk of hepatotoxicity increases. Concomitant use of rifampicin and halothane should be avoided.

Liver function should be closely monitored in patients receiving rifampicin and isoniazid concomitantly.

Para-aminosalicylic acid interferes with the absorption of rifampicin. Para-aminosalicylic acid preparations containing bentonite (hydrosilicate of aluminum) should be prescribed no earlier than 4 hours after taking rifampicin.

Avoid combined use with HIV protease inhibitors (indinavir, nelfinavir).

It should also be taken into account that rifampicin interacts with contrast agents used in cholecystography. Under its influence, the results of radiographic studies may be distorted.

special instructions

Continuous administration of rifampicin is better tolerated than intermittent administration (2-3 times a week).

Monotherapy for tuberculosis with rifampicin is often accompanied by the development of pathogen resistance to the antibiotic, so it should be combined with other antituberculosis drugs.

Use with caution in pulmonary heart failure of II-III degree, in debilitated patients, in patients who abuse alcohol, and with porphyria.

Treatment with rifampicin should be carried out under close medical supervision. With prolonged administration, phlebitis may develop. With the development of thrombocytopenia, purpura, hemolytic anemia, renal failure and other serious adverse reactions, the administration of rifampicin is stopped. Precautions should be taken in case of renal failure at a dose of the drug more than 600 mg/day.

In patients with tuberculosis, liver function should be checked before starting treatment. In adults: The following parameters should be checked: liver enzymes, bilirubin, creatinine, complete blood count and platelet count. In patients with impaired liver function, the drug should be taken only when necessary and under close medical supervision. In such individuals, it is necessary to adjust the dose of the drug and monitor liver function, especially alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Studies should be carried out before starting therapy, weekly for 2 weeks, then every 2 weeks for the next 6 weeks. If signs of liver dysfunction appear, the drug should be discontinued. Other anti-tuberculosis drugs should be considered after consulting a specialist. If rifampicin is reintroduced after normalization of liver function, liver function should be monitored daily. In patients with impaired liver function, in elderly patients, in debilitated patients, caution should be exercised when used simultaneously with isoniazid (the risk of hepatotoxicity increases).

In some patients, hyperbilirubinemia may occur in the first days of treatment. A moderate increase in bilirubin and/or transaminase levels is not an indication for interruption of treatment. It is necessary to dynamically monitor liver function and the clinical condition of the patient. Rifampin may interfere with the bile flow of the contrast agent used for gallbladder imaging due to competition for bile flow. Thus, the study must be carried out before administering the drug.

Because of the possibility of an immunological reaction, including anaphylactic shock, occurring in connection with intermittent therapy, patients should be closely monitored and advised of the dangers of intermittent treatment.

With long-term use of the drug, it is necessary to monitor the blood count due to the possibility of developing leukopenia.

In the case of prophylactic use in meningococcal bacilli carriers, strict monitoring of the patient's health is necessary in order to promptly identify symptoms of the disease in the event of resistance to rifampicin. During the treatment period, microbiological methods for determining the concentration of folic acid and vitamin B 12 in blood serum should not be used. Alternative methods of analysis need to be considered. Taking the drug can enhance the metabolism of endogenous substrates, including adrenal hormones, thyroid hormones and vitamin D.

Pregnancy and lactation period

In animal studies, rifampicin has been shown to have a teratogenic effect. The drug crosses the placental barrier, but its effect on the human fetus is unknown.

Women of childbearing age need reliable contraception (including non-hormonal) during treatment.

The use of rifampicin is contraindicated during pregnancy and lactation.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms.

During the treatment period, you should avoid driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: nausea, vomiting, abdominal pain, itching, headache, increased lethargy, increased activity of liver enzymes and/or bilirubin, brownish-red or orange coloration of the skin, urine, sweat, saliva, tears, feces (color intensity is proportional to the amount of rifampicin taken) , with liver disease, loss of consciousness may occur, in pediatric practice, facial or periorbital edema is possible, hypotension, sinus tachycardia, ventricular arrhythmia, convulsions, cardiac arrest and even death are possible.

The minimum acute or toxic dose has not been established. However, non-fatal acute overdoses in adults range from 9 to 12 g of rifampicin. Fatal acute overdoses in adults range from 14 to 60 g. Some fatal cases of rifampicin poisoning have been associated with alcohol consumption.

Treatment - symptomatic (there is no specific antidote): gastric lavage, inducing vomiting, taking activated charcoal, for nausea and vomiting - antiemetic drugs, hemodialysis, forced diuresis.

Release form and packaging

10 capsules per blister pack made of polyvinyl chloride film and printed varnished aluminum foil.

2 blister packs each, together with instructions for medical use in the state and Russian languages, are placed in cardboard packaging for consumer packaging.

Primary or secondary packaging, together with the appropriate number of instructions for medical use in the state and Russian languages, is placed in a corrugated cardboard box.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

Keep out of the reach of children!

Shelf life

Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

Pavlodar Pharmaceutical Plant LLP.

Registration Certificate Holder

Pavlodar Pharmaceutical Plant LLP, Kazakhstan

Address of the organization that accepts claims from consumers regarding the quality of products (goods) on the territory of the Republic of Kazakhstan )

Pavlodar Pharmaceutical Plant LLP

Kazakhstan, Pavlodar, 140011, st. Kamzina, 33.

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