Pharmacodynamics and pharmacokinetics
Low concentrations of the drug have a bactericidal effect on chlamydia, mycobacterium tuberculosis, rickettsia, legionella, and mycobacterium leprosy. High concentrations of the drug are active against gram-negative flora.
Rifampicin is a first-line anti-tuberculosis drug. High activity is observed when exposed to staphylococci, clostridia, gonococci, meningococci. The drug acts on extracellular as well as intracellular bacteria.
The mechanism of action is based on the inhibition of RNA polymerase of microorganisms. Cross-resistance with other antibacterial agents has not been recorded. With drug monotherapy, rapid development of selection of microorganisms to the antibiotic is observed.
Rifampicin[edit | edit code]
Rifamycins are a group of related, structurally complex macrocyclic antibiotics produced by Streptomyces mediterranei (Farr, 2000), and the semisynthetic compounds fampicin, rifabutin, rifapentine derived from them). Rifampicin is a derivative of rifamycin B.
Chemical properties[edit | edit code]
Rifampicin is soluble in organic solvents and aqueous acid solutions. Its structure formula is as follows:
Structural formula of rifampicin
Antimicrobial activity[edit | edit code]
Rifampin inhibits the growth of many gram-negative (Escherichia coli, Pseudomonas spp., Klebsiella spp., indole-positive and indole-negative Proteus spp.) and most gram-positive bacteria. It is very active against staphylococci, including Staphylococcus aureus (MIC ranges from 0.003 to 0.012 μg/ml), works well against Neisseria meningitidis and Haemophilus influenzae (MIC ranges from 0.1 to 0.8 μg/ml), and also has pronounced bacteriostatic effect against Legionella spp. (both in cell culture and in animal experiments).
The MIC for Mycobacterium tuberculosis is 0.005-0.2 μg/ml; for Mycobacterium kansasii it is 0.25-1 μg/ml. The growth of most strains of Mycobacterium scrofulaceum and Mycobacterium avium-intracellulare is inhibited at a rifampicin concentration of 4 µg/ml, although some strains can grow even at a rifampicin concentration of 16 µg/ml. Mycobacterium fortuitum is extremely resistant to the drug. In vitro, rifampicin enhances the antituberculosis activity of streptomycin and isoniazid, but not ethambutol (Hobby and Lenert, 1972).
Stability[edit | edit code]
In vitro, microorganisms can quickly acquire resistance to rifampicin. The probability of the emergence of resistant strains of Mycobacterium tuberculosis is 1 in 107-108. Typically, resistance is caused by a mutation between codons 507 and 533 of the rB gene, which encodes bacterial RNA polymerase (Blanchard, 1996). The same thing apparently happens in vivo, which is why rifampicin is always prescribed to patients with tuberculosis in combination with other anti-tuberculosis drugs. The failure of attempts to eliminate the carriage of meningococci using rifampicin was also due to drug resistance: resistant strains appeared within 2 days. after starting treatment. Some rifampicin-resistant strains have reduced virulence. In patients who have not previously taken anti-tuberculosis drugs, rifampicin-resistant strains of Mycobacterium tuberculosis are isolated extremely rarely, in less than 1% of cases (Cauthen et al., 1988).
Mechanism of action[edit | edit code]
Rifampicin inhibits bacterial RNA polymerase, forming a stable complex with it and preventing the initiation (but not elongation) of transcription. The target of rifampicin is the β-subunit of RNA polymerase; although it only binds to the holoenzyme. Nuclear RNA polymerase of eukaryotic cells is insensitive to rifampicin, but at concentrations significantly higher than bactericidal levels, rifampicin inhibits the synthesis of mitochondrial RNA. At high concentrations, rifampicin also inhibits the activity of viral PH K-polymerases and reverse transcriptases. Rifampicin has a bactericidal effect on both extracellular and intracellular microorganisms.
Side effects of Rifampicin
Digestive tract: pseudomembranous enterocolitis , vomiting, loss of appetite, nausea, increased levels of liver enzymes, hepatitis , hyperbilirubinemia , diarrhea , erosive gastritis .
Nervous system: disorientation , decreased visual acuity, headache, ataxia .
Genitourinary system: interstitial nephritis , nephronecrosis .
hyperuricemia , myasthenia , leukopenia , allergies , exacerbation of gout , dysmenorrhea is possible .
If the drug is not used regularly, it is possible to develop a flu-like condition and the following side effects: myalgia , chills , fever , dizziness , headaches .
Instructions for use of Rifampicin (Method and dosage)
The drug is taken orally and administered intravenously.
Rifampicin tablets, instructions for use
Take half an hour before meals, on an empty stomach.
In the treatment of tuberculosis, this medicine must be combined with other anti-tuberculosis medications ( Ethambutol , Pyrazinamide , Isoniazid ). Adults are prescribed 10 mg/kg once every 24 hours. No more than 1200 mg per day, for children - no more than 600 mg.
Combination of tuberculosis with HIV , tuberculosis damage to the spinal column with neurological symptoms, disseminated tuberculosis, tuberculous meningitis: 2 months Rifampicin is used with Pyrazinamide , Isoniazid , Ethambutol , Streptomycin , the next 7 months the antibiotic is combined with Isoniazid .
If mycobacteria are detected in sputum or pulmonary tuberculosis, the patient is prescribed one of three antimicrobial therapy regimens, used in combination with other drugs.
Multibacillary types of leprosy (borderline, lepromatous, mixed): 600 mg once a month along with Dapsone 100 mg once a day and clofazimine (300 mg once a month, 50 mg daily).
Pausibacillary types of leprosy (borderline tuberculoid, simple tuberculoid): once a month 600 mg together with Dapsone 100 mg daily, the course of therapy is designed for six months.
Therapy for brucellosis : a single dose of 900 mg on an empty stomach in the morning along with Doxycycline , the course is designed for 45 days.
Prevention of meningococcal meningitis : every 12 hours - 600 mg, course for 2 days.
Using the solution
IV adults are prescribed 600 mg per day, children 10 mg per kg once a day. The maximum dose for intravenous administration is 600 mg.
Rifampicin 150 mg No. 100 Capsules
Rifampicin 150 mg No. 100 capsules
General characteristics international and chemical names: rifampicin; 3-(4-Methyl-1-piperazinyl)imino]methyl]rifamycin; Basic physicochemical properties of 150 mg tablets: light pink-brown, round, biconvex, film-coated tablets; 300 mg tablets: light pink-lilac, round, biconvex, film-coated tablets, with a break line on one side; 450 mg tablets: red, round, biconvex, film-coated tablets; Composition 1 tablet contains rifampicin 150 mg or 300 mg or 450 mg; excipients: for 150 mg tablets: corn starch, colloidal silicon dioxide, sodium lauryl sulfate, microcrystalline cellulose, croscarmellose sodium, purified talc, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide (E 171), dye – red iron oxide (E 172); for tablets of 300 mg: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, corn starch, sodium starch glycolate, purified talc, hydroxypropyl methylcellulose, titanium dioxide (E 171), pink-lilac dye, red iron oxide dye (E 172 ); for tablets of 450 mg: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, corn starch, sodium starch glycolate, talc, hydroxypropyl methylcellulose, titanium dioxide (E 171), dye - red iron oxide (E 172). Release form: Film-coated tablets. Pharmacotherapeutic group Agents acting on mycobacteria. ATC code J04AB02. Pharmacological action Rifampicin is a semisynthetic broad-spectrum antibiotic. Rifampicin has a bacteriostatic and, in high concentrations, a bactericidal effect. Pharmacodynamics. Selectively inhibits DNA-dependent RNA polymerase of sensitive microorganisms. Active against intracellular and subcellular microorganisms. Highly active against Mycobacterium tuberculosis, it is a first-line anti-tuberculosis drug. Active against gram-positive microorganisms: Staphylococcus spp., including multi-resistant ones; Streptococcus spp., Bacillus anthracis, Clostridium spp., as well as against some gram-positive microorganisms: Neisseria meningitidis, Haemophilus influenzae, Brucella spp., Legionella pneumophila. Acts on pathogens Brucella spp., Legionella pneumophila, Salmonella typhi, Mycobacterium leprae, Chlamydia trachomatis, Rickettsia prowazekia. Resistance to rifampicin develops rapidly. Cross-resistance with other anti-tuberculosis drugs (except for other rifamycin) was not observed. Pharmacokinetics. Rifampicin is well absorbed from the gastrointestinal tract. Eating reduces the absorption of the drug. The maximum concentration in the blood is reached 2-3 hours after ingestion. At a therapeutic level, the concentration of the drug when taken orally is maintained for 8-12 hours, and for highly sensitive pathogens - for 24 hours. Plasma protein binding is high - 84-91%. Rifampicin penetrates well into tissues and body fluids and is found in therapeutic concentrations in pleural exudate, sputum, cavity contents, and bone tissue. It penetrates the BBB only in case of inflammation of the meninges. Penetrates the placenta and is excreted in breast milk. The highest concentration of the drug is created in the tissues of the liver and kidneys. Metabolized in the liver to form a pharmacologically active metabolite. The half-life (T½) is 3-5 hours. It is an autoinducer - it accelerates its metabolism in the liver, resulting in systemic clearance of 6 l/h after taking the first dose, increasing to 9 l/h after repeated dosing. After a few days of repeated administration, bioavailability decreases; half-life after repeated administration is shortened to 1-2 hours. Excreted primarily in bile, 80% as a metabolite; kidneys – 20%. In patients with impaired renal excretory function, T½ is prolonged only in cases where its dose exceeds 600 mg. In patients with impaired liver function, there is an increase in plasma rifampicin concentrations and a prolongation of T½. Indications for use Tuberculosis of various localizations (all forms, including tuberculous meningitis) as part of combination therapy. Infectious and inflammatory diseases caused by microorganisms sensitive to the drug (primarily multi-resistant staphylococci), including: leprosy (in combination with dapsone - multibacillary types of the disease); osteomyelitis; pneumonia, bronchitis; otitis; cholecystitis; pyelonephritis; meningococcal carriage, meningococcal meningitis (prevention for persons who have been in close contact with patients with meningococcal meningitis); gonorrhea. Method of administration and dosage: Inside, on an empty stomach. Rifampicin is taken 30 minutes - 1 hour before meals, 1 time per day. When treating tuberculosis, adult patients weighing less than 50 kg are prescribed Rifampicin at a dose of 450 mg; patients weighing more than 50 kg are prescribed 600 mg/day in 1 dose (if Rifampicin is poorly tolerated, the daily dose can be divided into 2 doses); the maximum daily dose is 1.2 g. The duration of treatment for tuberculosis can be 12 months or more. Children over three years old are prescribed Rifampicin at a dose of 10 mg/kg body weight/day in 1-2 doses; maximum dose for children is 450 mg. For the treatment of leprosy against the background of combination therapy, Rifampicin is used according to two regimens: 1) the daily dose (300-450 mg) is taken in 1 dose, and if poorly tolerated, in 2 doses. Duration of treatment – 3-6 months, courses are repeated with an interval of 1 month; 2) the daily dose (450 mg) is taken in 2-3 doses over 2-3 weeks with an interval of 2-3 months for 1-2 years (or the same dose 2-3 times a week for 6 months). For the treatment of infectious diseases caused by sensitive microorganisms, it is prescribed in combination with other antimicrobial agents. Daily dose for adults – 450-900 mg/day; for children and infants – 8-10 mg/kg. The frequency of administration is 2-3 times a day. For the treatment of brucellosis – 900 mg/day once, in the morning on an empty stomach, in combination with doxycycline; The 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 over 1 month – 10 mg/kg; for newborns – 5 mg/kg. For acute gonorrhea, it is prescribed orally at a dose of 900 mg/day once for 1-2 days. Side effects With daily use of Rifampicin, its tolerability is better than with intermittent treatment. From the digestive system: nausea, vomiting, diarrhea, loss of appetite, erosive gastritis, increased levels of liver transaminases, bilirubin in the blood plasma, pseudomembranous enterocolitis, hepatitis. From the hematopoietic system: rarely - thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, hemolytic anemia. From the central nervous system: headache, decreased visual acuity, ataxia, impaired coordination of movements, disorientation. From the urinary system: necrosis of the renal tubules, interstitial nephritis, acute renal failure. From the endocrine system: dysmenorrhea. Allergic reactions: urticaria, Quincke's edema, bronchospasm. Influenza-like syndrome: arthralgia, fever, myalgia (with intermittent or irregular therapy or when resuming treatment after a break). Others: red-brown coloring of urine, feces, saliva, sputum, sweat, tears. Contraindications : liver and kidney disease (with reduced excretory function); recent (less than 1 year) infectious hepatitis; severe renal dysfunction; pregnancy, breastfeeding period; hypersensitivity to rifampicin or other components of the drug. Overdose Symptoms: pulmonary edema, confusion, convulsions. Treatment: gastric lavage, administration of activated carbon; symptomatic therapy, forced diuresis. It is excreted during peritoneal dialysis and hemodialysis. Peculiarities of use In newborns and premature infants, rifampicin is used only for health reasons. With long-term use of the drug, systematic monitoring of peripheral blood patterns and liver and kidney function is indicated. When treating non-tuberculosis infections, rapid development of microbial resistance is possible. In the case of prophylactic use of bacilli and meningococcus, close monitoring of patients is necessary in order to promptly identify symptoms of the disease in the event of resistance to rifampicin. In the case of the development of influenza-like syndrome, uncomplicated by thrombocytopenia, hemolytic anemia, bronchospasm, shortness of breath, shock and renal failure, in patients receiving the drug according to an intermittent regimen, the possibility of switching to daily dosing should be considered. If the above serious complications are observed, rifampicin should be discontinued. If it is necessary to resume treatment with Rifampicin after a break, then you should start with a dose of 75 mg/day, gradually increasing it by 75 mg/day until the desired dose is reached. In this case, renal function should be monitored. During the treatment period, microbiological methods for determining the concentration of folic acid and vitamin B12 in blood serum should not be used. During treatment, the skin, sputum, sweat, feces, tear fluid, and urine become orange-red. Can permanently stain soft contact lenses. Use with caution in debilitated patients. Use during pregnancy and lactation. Women of reproductive age should use reliable methods of contraception (oral hormonal contraceptives and additional non-hormonal methods of contraception) during treatment. Rifampin is excreted in breast milk. If necessary, use during lactation should stop breastfeeding. Interaction with other drugs and other types of interactions Rifampicin helps to reduce the activity (causes induction of liver enzyme systems, accelerates metabolism) theophylline, oral anticoagulants, oral antidiabetic drugs, hormonal contraceptives, digitalis drugs, β-blockers, enalapril, disopyramide, mexiletine, verapamil, phenytoin, quinidine, corticosteroids, chloramphenicol, dapsone, azathioprine, cimetidine, antifungal drugs (ketoconazole, itraconazole), benzodiazepines, cyclosporine A. Antacids, opiates, anticholinergics and ketoconazole reduce (in case of simultaneous oral administration) the bioavailability of rifampicin. Isoniazid and/or pyrazinamide increase the incidence and severity of liver dysfunction more than with rifampicin alone in patients with a history of liver disease. PAS preparations containing bentonite (hydrosilicate of aluminum) should be prescribed no earlier than 4 hours after taking Rifampicin, because absorption may be impaired. You cannot use a test with a bromsulfalein load, since rifampicin competitively inhibits its excretion. Conditions and shelf life Store at a temperature not exceeding 25ºС, out of reach of children, in a dry place protected from light. Shelf life – 3 years. Conditions of release By prescription.
Interaction
Rifampicin reduces the activity of digitalis drugs, oral hypoglycemic medications, anticoagulants, contraceptives, antiarrhythmic drugs ( tocainide , pyrmenol , disopyramide , mexiletine , quinidine ), phenytoin , dapsone , glucocorticosteroids, ketoconazole , chloramphenicol , sex hormones, benzodiazepines, nor triptyline , , cyclosporine , cimetidine , Enalapril , BMCC, beta-blockers, Azathioprine (rifampicin can accelerate metabolism due to the induced induction of certain enzymes of the liver system).
Ketoconazole , anticholinergics, opiates and antacids reduce the bioavailability of the antibiotic.
When taking Pyrazinamide or Isoniazid , the hepatotoxic effect increases.
The drug Pask can be prescribed 4 hours after using Rifampicin to prevent absorption.
special instructions
Antibacterial therapy can lead to a reddish coloration of urine, tears, feces, sweat, skin and sputum. Permanent staining of contact lenses is possible.
Intravenous infusions of Rifampicin are carried out under blood pressure monitoring. Long-term therapy leads to the formation of phlebitis . To prevent resistance, the drug is used in combination with other antibiotics and antimicrobial agents.
When registering a flu-like syndrome (without bronchospasm , hemolytic anemia , shortness of breath, renal failure , shock, thrombocytopenia ) in patients who are taking medication on an intermittent regimen, the attending physician should consider switching to daily use of an antibiotic. In this case, the dose increase occurs slowly, titration takes 3-4 days. Regular monitoring of the state of the renal system is required, and the use of glucocorticosteroids is possible.
Rifampin during pregnancy is used exclusively for health reasons. Prescribing an antibiotic in the last days of pregnancy can cause bleeding in the newborn, as well as postpartum bleeding in the mother. , vitamin K is recommended . Women during the period of antibacterial therapy should be reliably protected from pregnancy.
When carrying out prophylaxis against meningococcal bacilli, strict control over the group is required for timely detection of symptoms in the development of resistance to the antibacterial drug.
Long-term therapy requires regular monitoring of the state of the hepatic system and peripheral blood.
The medication affects the level of vitamin B12 and folic acid in the blood serum.
Pharmacokinetics[edit | edit code]
The maximum serum concentration of rifampicin is achieved 2-4 hours after oral administration and varies widely. When taken at a dose of 600 mg, it is about 7 mcg/ml. Food and aminosalicylic acid slow the absorption of rifampicin, reducing its serum concentration.
When administered simultaneously, the interval between taking rifampicin and aminosalicylic acid should be 8-12 hours (Radner, 1973).
After absorption from the gastrointestinal tract, rifampicin quickly enters the bile and participates in the enterohepatic circulation. At the same time, it is gradually deacetylated, and after 6 hours only the deacetylated derivative of rifampicin is detected in the bile. The latter almost completely retains its antimicrobial activity, but is poorly reabsorbed in the intestine and excreted in the feces. The half-life (T1/2) of rifampicin ranges from 1.5 to 5 hours. In liver diseases, this figure increases, and in individuals with low activity of acetylating enzymes who are simultaneously receiving isoniazid, it decreases.
During treatment, the elimination of rifampicin is accelerated (by approximately 40% for the first 14 days) due to the induction of liver microsomal enzymes that deacetylate the drug. Up to 30% of rifampicin is excreted in the urine, 60-65% in feces, and the unchanged drug accounts for less than half of this amount. In case of renal failure, the dose of rifampicin is not reduced.
Rifampicin is distributed throughout the body, reaching therapeutic concentrations in many tissues and body fluids, including the CSF (Sippel et al., 1974). Patients should be warned that the drug turns urine, feces, saliva, sputum, tears and sweat orange. The metabolism of rifampicin is described in more detail, for example, in Furesz (1970), Farr (2000).
Rifampicin price, where to buy
The price of Rifampicin in 150 mg capsules is about 60 rubles. per pack 20 pcs.
A package of Rifampicin 10 ampoules of 150 mg each costs approximately 500 rubles.
- Online pharmacies in RussiaRussia
LuxPharma* special offer
- Rifampicin caps.
150 mg 100 pcs 3950 rub. order
