Expiration date: 02/2029
Packaging and release form
Lyophilizate for the preparation of a solution for infusions of 150 mg in ampoules with a capacity of 5 ml - 10 pcs per pack.
Composition
Composition per ampoule:
Active ingredient: rifampicin sodium 154.01 mg, obtained according to the following formula: rifampicin - 150.0 mg and sodium hydroxide - 4.01 mg;
auxiliary substances. ascorbic acid - 14.0 mg; sodium sulfite - 2.8 mg; sodium hydroxide solution 2 M - up to pH 8.0-9.0.
The dosage form
is a porous mass or powder of brownish-red color, marbling is allowed, odorless.
Pharmacotherapeutic group
antibiotic-rifamycin
Pharmacodynamics
A semi-synthetic broad-spectrum antibiotic, antituberculous drug of the first series. In low concentrations, it has a bactericidal effect on Mycobacterium tuberculosis, Brucella spp., Chlamydia trachomatis, Legionella pneumophila, Rickettsia typhi, Mycobacterium leprae, in high concentrations - on some gram-negative microorganisms. It is characterized by high activity against Staphylococcus spp. (including penicillinase-forming and many strains of methicillin-resistant), Streptococcus spp., Clostridium spp., Bacillus anthracis; gram-negative cocci: Neisseria meningitidis, Neisseria gonorrhoeae. It acts on gram-positive bacteria in high concentrations. It is active against intracellularly and extracellularly located microorganisms. Selectively inhibits DNA-dependent RNA polymerase of sensitive microorganisms. With rifampicin monotherapy, the selection of rifampicin-resistant bacteria is relatively rapid. Cross-resistance with other antibiotics (with the exception of other rifamycins) does not develop.
Pharmacokinetics
With intravenous drip, the maximum concentration (Cmax) is observed by the end of the infusion. With intravenous administration, the therapeutic concentration is maintained for 8-12 hours, for highly sensitive pathogens - for 24 hours. The binding to plasma proteins is 84-91%. It is rapidly distributed to organs and tissues (the highest concentration is in the liver and kidneys), penetrates into bone tissue, and the concentration in saliva is 20% of plasma. It is found in therapeutic concentrations in pleural exudate (protein-rich fluid accumulating between the membranes surrounding the lungs), sputum, and contents of cavities (cavities in the lungs formed as a result of tissue necrosis). The highest concentration of the drug is created in the tissues of the liver and kidneys.
Penetrates through the blood-brain barrier only in case of inflammation of the meninges. It penetrates through the placenta (the concentration in fetal plasma is 33% of the concentration in maternal plasma) and is excreted in breast milk (breast-fed infants receive no more than 1% of the therapeutic dose of the drug). It is metabolized in the liver to form a pharmacologically active metabolite, 25-O-deacetylrifampicin. It is an auto-inducer - it accelerates its metabolism in the liver, resulting in a systemic clearance of 6 l / h after the first dose, which increases to 9 l / h after repeated administration. It is mainly excreted in bile, 80% as a metabolite; 20% by the kidneys.
In patients with impaired renal excretory function, the elimination half-life is prolonged only when its doses exceed 600 mg. It is excreted during peritoneal dialysis and hemodialysis. In patients with impaired liver function, there is an increase in the concentration of rifampicin in plasma and an elongation of the half-life.
Indications
Tuberculosis (all forms) - as part of combination therapy.
Leprosy (multibacillary types of the disease) - in combination with other antimicrobial drugs active against Mycobactcrium leprae. Infectious diseases caused by microorganisms sensitive to rifampicin (in cases of resistance to other antibiotics and as part of combined antimicrobial therapy; after excluding the diagnosis of tuberculosis and leprosy).
Brucellosis is used in combination therapy with an antibiotic of the tetracycline group (doxycycline).
Meningococcal meningitis (prevention in people who have been in close contact with meningococcal meningitis patients: in the case of Neisseria meningitidis bacilli).
Contraindications
Hypersensitivity to rifampicin and other rifamycins or to any of the components of the drug; recent jaundice (less than
1 year old) infectious hepatitis; pregnancy (only for "vital" indications); breastfeeding; chronic renal failure (CRF); pulmonary heart failure II-III degrees; children under 1 year old.
With caution
In patients who abuse alcohol; with indications of liver disease in the anamnesis; with porphyria; in exhausted patients when resuming treatment with rifampicin after a break.
Use during pregnancy during breastfeeding
During pregnancy, it is used only if the intended benefit to the mother exceeds the potential risk to the fetus.
Therapy during pregnancy (especially in the first trimester) is possible only for
"vital" indications. When prescribed in the last weeks of pregnancy, there may be postpartum bleeding in the mother and bleeding in the newborn. In this case, vitamin K is prescribed.
If it is necessary to use the drug during lactation, breastfeeding should be discontinued.
Method of administration and dosage
The drug is administered intravenously, the rate of administration is 60-80 drops / min. Intravenous administration of the drug is recommended for acute progressive and widespread forms of destructive pulmonary tuberculosis, severe purulent-septic processes, if it is necessary to quickly create high concentrations of the drug in the blood and in the focus of infection, in cases where ingestion of the drug is difficult or poorly tolerated by patients.
The dose and duration of therapy should be adjusted depending on the type and severity of the infection and the patient's condition. The following dosage regimens are recommended:
Adults and children over 12 years old. 10 mg / kg of body weight, the maximum daily dose is 600 mg.
Children from 1 to 6 years of age: 15 mg/kg of body weight per day.
Children from 6 to 12 years of age. 10-20 mg / kg of body weight per day, with long-term therapy, the daily dose should not exceed 450 mg.
For the treatment of tuberculosis. For intravenous administration, the daily dose for adults is 450 mg; for severe, rapidly progressive forms, 600 mg is administered in one dose.
The duration of intravenous administration depends on tolerability and is 1 month or more (followed by a switch to oral administration). The total duration of the drug's use in tuberculosis is determined by the effectiveness of treatment and can reach one year.
In the treatment of tuberculosis, it is combined with at least one anti-tuberculosis drug (isoniazid, pyrazinamide, ethambutol, streptomycin). Adults with a body weight of less than 50 kg - 450 mg / day; 50 kg and more - 600 mg / day.
For children over 1 year of age - 10-20 mg / kg / day, the maximum daily dose is 600 mg. With tuberculous meningitis, disseminated tuberculosis, spinal lesions with neurological manifestations. When tuberculosis is combined with HIV infection, the total duration of treatment is 9 months. The drug is used daily, for the first 2 months in combination with isoniazid, pyrazinamide, ethambutol (or streptomycin), 7 months in combination with isoniazid.
In the case of pulmonary tuberculosis and the detection of mycobacteria in sputum, the following 3 regimens are used (all lasting 6 months):
1. The first 2 months - as indicated above; 4 months - daily in combination with isoniazid.
2. The first 2 months - as indicated above; 4 months - daily in combination with isoniazid, 2-3 times during each week.
3. Throughout the course, it is taken in combination with isoniazid, pyrazinamide, ethambutol (or streptomycin) 3 times a week. In cases where anti-tuberculosis drugs are used 2-3 times a week (as well as in case of exacerbation of the disease or ineffectiveness of therapy), their use should be carried out under the supervision of medical personnel.
For infections of non-tuberculosis etiology caused by sensitive microorganisms, the daily dose for adults is 300-900 mg (maximum - 1.2 g), for children over 1 year - 10-20 mg / kg. The daily dose is divided into 2-3 injections. The duration of treatment is set individually, depends on the effectiveness and can be 7-10 days. Intravenous administration should be discontinued as soon as possible for oral administration.
For the treatment of leprosy. For the treatment of multibacillar types of leprosy (lepromatous, borderline, borderline-lepromatous): adults - 600 mg once a month, children over 1 year - 10 mg / kg once a month in combination with other antimicrobial drugs active against Mycobacterium leprae. The minimum duration of treatment is 2 years.
For the treatment of multibacillary types of leprosy (tuberculoid and borderline tuberculoid): adults - 600 mg once a month, children over 1 year old
- 10 mg/ kg once a month in combination with other antimicrobial drugs active against Mycobacterium leprae. The duration of treatment is 6 months.
For the treatment of brucellosis in adults - 900 mg / day once in combination with doxycycline. The average duration of treatment is 45 days.
For the prevention of meningococcal meningitis 2 times a day for 2 days. Single doses: adults - 600 mg, children over 1 year - 10 mg / kg.
With impaired kidney and/or liver function. In patients with impaired renal excretory function and preserved liver function, dose adjustment is required only if it exceeds 600 mg / day.
Features of application after interruption of therapy. After discontinuation of therapy, rifampicin is prescribed with a gradual increase in dose. Monitoring of renal function is necessary, and the appointment of glucocorticosteroids is recommended if necessary.
Preparation of the solution
The contents of 1 ampoule / vial (150 mg rifampicin) are dissolved in 2.5 ml of water for injection, shaken vigorously until completely dissolved; the resulting solution is mixed with 125 ml of 5% dextrose solution. The rate of administration is 60-80 drops/min.
The contents of 1 vial (600 mg of rifampicin) are dissolved in 10 ml of water for injection, shaken vigorously until completely dissolved; the resulting solution is mixed with 500 ml of 5% dextrose solution. The injection rate is 60-80 drops/min.
Special instructions
During treatment, the skin, sputum, sweat, feces, tear fluid, and urine turn orange-red. It can permanently stain soft contact lenses. Intravenous infusion is carried out under the control of blood pressure; with prolonged administration, phlebitis may develop.
To prevent the development of microbial resistance, it must be used in combination with other antimicrobial drugs. If an influenza-like syndrome develops that is not complicated by thrombocytopenia, hemolytic anemia, bronchospasm, shortness of breath, shock, and renal failure, patients receiving the drug on an intermittent schedule should consider switching to daily intake. In these cases, the dose is increased slowly: 75-150 mg is prescribed on the first day, and the required therapeutic dose is reached in 3-4 days. If the above serious complications persist, rifampicin is discontinued. It is necessary to monitor kidney function; additional administration of glucocorticosteroids is possible.
In the case of preventive use in meningococcal
bacilli, strict monitoring of patients is necessary in order to identify the symptoms of the disease in a timely manner in case of resistance to rifampicin.
With prolonged use, systematic monitoring of peripheral blood and liver function is indicated.
Women of reproductive age should use reliable methods of contraception (oral hormonal contraceptives and additional non-hormonal methods of contraception) during treatment.
Microbiological methods for determining the concentration of folic acid and vitamin B12 in blood serum should not be used during treatment. A false positive result is possible in the immunological determination of opiates in the blood.
Influence on the ability to drive vehicles, mechanisms
During treatment, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.
Side effects
From the digestive system: nausea, vomiting, diarrhea, decreased appetite, abdominal pain, flatulence, erosive gastritis, pseudomembranous colitis; increased activity of "liver" transaminases and alkaline phosphatase in blood serum, hepatitis, jaundice, hyperbilirubinemia, acute pancreatitis.
Allergic reactions: urticaria, eosinophilia, angioedema, bronchospasm, arthralgia, fever.
Nervous system disorders: dizziness, headache, ataxia, disorientation, muscle weakness.
Urinary system disorders: nephronecrosis, interstitial nephritis.
From the organs of vision: decreased visual acuity, optic neuritis.
Others: leukopenia, dysmenorrhea, porphyria induction, myasthenia gravis, hyperuricemia, gout exacerbation.
Local reactions: phlebitis at the injection site.
With intermittent or irregular therapy, or when resuming treatment after a break, flu-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.
If any of the side effects listed in the instructions worsen, or you notice any other side effects not listed in the instructions, tell your doctor.
Drug interaction
Rifampicin induces cytochrome P450 isoenzymes, accelerating drug metabolism. and, accordingly, it removes the activity of indirect anticoagulants, oral hypoglycemic drugs, cardiac glycosides (digoxin), antiarrhythmic drugs (disopyramide, pyrmenol, quinidine, mexiletine, tocainide, propafenone), glucocorticosteroids, dapsone, hydantoines (phenytoin), carbamazepine, buspirone, barbiturates (phenobarbital, hexobarbital), some tricyclic antidepressants (nortriptyline), antiviral drugs (including nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, stavudine); (incl. non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine), benzodiazepines (diazepam), theophylline, chloramphenicol, antipsychotics (haloperidol), antifungal drugs (itraconazole, terbinafine), cyclosporine, azathioprine, beta-blockers (propranolol), blockers of "slow" calcium channels (nifedipine, verapamil, diltiazem), hypolipidemic drugs (simvastatin), antimalarial drugs (mefloquine), cytostatics (ta-moxifen), cyclooxygenase-2 inhibitors (celecoxib), losartan, enalapril, cyietidine, thyroxine, sex hormones.
Concomitant use with HIV protease inhibitors (indinavir, nelfinavir) should be avoided. Rifampicin accelerates the metabolism of estrogens and progestogens (reduces the effect of oral contraceptives).
With the simultaneous use of rifampicin (600 mg / day), ritonavir (100 mg twice daily) and saquinavir (1000 mg), severe hepatotoxicity may develop. When combined, rifampicin significantly reduces plasma concentrations of atazanavir, darunavir, fosamprenavir, saquinavir and tipranavir, which may lead to a decrease in antiviral activity.
Isoniazid and/or pyrazinamide increase the frequency and severity of liver dysfunction to a greater extent than with rifampicin alone in patients with previous liver disease.
Co-trimoxazole (sulfamethoxazole/trimethoprim) increases the concentration of rifampicin in the blood.
Rifampicin interacts with contrast agents used in cholecystography. Under its influence, the results of X-ray examinations may be distorted.
Overdose
Symptoms: pulmonary edema, lethargy, confusion, seizures.
Treatment: symptomatic therapy; forced diuresis.
Storage temperature
from 2℃ to 25℃
