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

Pharmacodynamics:Semisynthetic broad-spectrum antibiotic, antituberculous drug of the 1st series. At low concentrations, it has a bactericidal effect on Mycobacterium tuberculosis, Brucella spp., Chlamydia trachomatis, Legionella pneumophila, Rickettsia typhi, Mycobacterium leprae; in high concentrations - on some gram-negative microorganisms. Characterized by high activity against Staphylococcus spp. (including penicillinase-forming and many strains of methicillin-resistant), Streptococcus spp., Clostridium spp., Bacillus anthracis; Gram-negative coca: Neisseria meningitidis, Neisseria gonorrhoeae. Gram-positive bacteria acts in high concentrations. It is active with respect to intracellular and extracellularly located microorganisms. Selectively inhibits the 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 the other rifamycins) does not develop.

Pharmacokinetics:

At intravenous drip introduction the maximum concentration (Сmах) is observed by the end of infusion. At the therapeutic level, the concentration of the drug with intravenous administration is maintained for 8-12 hours, for highly sensitive pathogens - within 24 hours. The connection with blood plasma proteins is 80 - 90%. Rifampicin penetrates well into tissues and body fluids and is found in therapeutic concentrations in pleural exudate (accumulating between the membranes surrounding the lungs, a protein-rich fluid), sputum, cavern contents (cavities in the lungs resulting from necrosis of tissue), bone tissue. The greatest concentration of the drug is created in the tissues of the liver and kidneys.

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

Metabolized in the liver with the formation of pharmacologically active metabolite-25-O-deacetyltrifampicin. It is an autoinducer - it accelerates its metabolism in the liver, resulting in a systemic clearance of 6 l / h after the first dose, increases to 9 l / h after repeated administration. It is excreted mainly with bile, 80% - in the form of a metabolite; kidneys - 20%.

In patients with impaired renal excretory function, the half-life period (T1 / 2) is prolonged only when its doses exceed 600 mg. It is excreted in peritoneal dialysis and hemodialysis. In patients with impaired hepatic function, an increase in rifampicin plasma concentration and an elongation of T1 / 2 were noted. Resistance to rifampicin develops rapidly. Cross-resistance with other antibiotics is not observed (with the exception of rifamycin).

Indications:Tuberculosis (all forms) - as part of combination therapy.

Leprosy (multibacillary types of the disease) - in combination with other antimicrobial drugs, active against Mycobacterium leprae.

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

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

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

Contraindications:

- increased sensitivity to rifampicin and other rifamycins or to any of the components of the drug;

- jaundice, recently transferred (less than a year) infectious hepatitis;

- chronic renal failure;

- pulmonary heart failure, II - III degree;

- pregnancy (only for life indications);

- lactation period;

- children under the age of 1 year.

Carefully:They are used with caution in patients who abuse alcohol, with evidence of liver disease in the anamnesis, in depleted patients with the resumption of rifampicin treatment after a break.

Pregnancy and lactation:The use of the drug during pregnancy is possible if the intended benefit for the mother exceeds the potential risk to the fetus (only for "vital" indications). During the period of drug use it is necessary to stop breastfeeding.

Dosing and Administration:Intravenous (IV) is drip, the rate of administration is 60-80 cap / min. Intravenous administration of the drug is recommended for acute and progressive forms of destructive pulmonary tuberculosis, severe purulent-septicif necessary, the rapid creation of high concentrations of the drug in the blood and in the focus of the infection, in cases where taking the drug inside is difficult or badly tolerated by patients. Dosage regimen is set by the doctor individually depending on the severity of the disease and the patient's response to treatment. If the doctor is not assigned otherwise, the following dosing regimens are recommended:

Adults and children over 12 years of age:

10 mg / kg body weight, the maximum daily dose - 600 mg.

Children over 1 year and up to 6 years of age: 15 mg / kg of body weight per day.

Children from 6 to 12 years: 10-20 mg / kg per day, with long-term therapy, the daily dose should not exceed 450 mg.

For the treatment of tuberculosis With IV administration, the daily dose for adults is 450 mg, with severe, rapidly progressive forms - 600 mg is administered in one dose. The duration of IV administration depends on the tolerance and is 1 month or more (with the subsequent transition to oral administration).The total duration of use for tuberculosis is determined by the effectiveness of treatment and can reach 1 year.

For the treatment of tuberculosis, at least one antituberculous drug is combined (isoniazid, pyrazinamide, ethambutol, streptomycin).

Adults with a body weight of less than 50 kg - 450 mg / day; 50 kg and more - 600 mg / day.

Children older than 1 year 10-20 mg / kg / day, the maximum daily dose - 600 mg. With tuberculous meningitis, disseminated tuberculosis, spinal cord injury with neurological manifestations, with the combination of tuberculosis with HIV infection, the total duration of treatment is 9 months, the drug is used daily, the first 2 months in combination with isoniazid, pyrazinamide, ethambutol (or streptomitsin), 7 months - in combination with isoniazid.

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

- The first 2 months are as above; 4 months - daily in combination with isoniazid.

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

- Throughout the course - the reception in combination with isoniazid, pyrazinamide, ethambutol (or streptomycin) 3 times during each week.In those cases when anti-TB drugs are used 2-3 times a week (as well as in case of an exacerbation of the disease or inefficiency of therapy), their application must be carried out under the supervision of medical personnel.

With infections of non-tuberculous etiology, caused by the sensorymicroorganisms, 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 of cucumbers to 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 multibacillary 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 antimicrobials active against Mykobacterium 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 - 10 mg / kg once a month in combination with other antimicrobials active against Mykobacterium leprae. Duration of treatment - 6 months.

For the treatment of brucellosis 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 to adults - 600 mg, children over 1 year - 10 mg / kg.

Patients with impaired hepatic and / or renal function.

Patients with impaired renal excretory function and preserved liver function dose adjustment is required only when it exceeds 600 mg / day.

Features of application after interruption of therapy

After interruption of therapy rifampicin is prescribed with a gradual increase in the dose. It is necessary to monitor the function of the kidneys, if necessary, we recommendadministration of glucocorticosteroids.

Preparation and administration of drug solutions: in the vial with the drug is added water for injection, vigorously shaken until completely dissolved; The resulting solution is mixed with an infusion solution: 5% dextrose solution, or 5% fructose solution, or 0.9% sodium chloride solution. Water for injection and infusion solutions are used in the following dilution:

Dose of the drug in the vial	The volume of water for injection	The volume of the infusion solution
150 mg	2.5 ml	125 ml
300 mg	5 ml	250 ml
450 mg	7.5 ml	375 ml
600 mg	10 ml	500 ml

The rate of administration is 60-80 drops per minute.

Side effects:

Side effects are shown below in terms of frequency of decrease in incidence: often (1-10% of patients), infrequently (0.1-1%), rarely (0.01-0.1%) very rarely (less than 0.01%), including individual messages.

Allergic reactions: urticaria, eosinophilia, Quincke's edema, bronchospasm, arthralgia, fever.

From the gastrointestinal tract: often: nausea, vomiting, diarrhea, anorexia; rarely: erosive gastritis, pseudomembranous colitis, increased activity of "liver" transaminases and alkaline phosphatase in the blood serum, hyperbilirubinemia, hepatitis, acute pancreatitis,

From the side of the organs of vision: rarely: decreased visual acuity.

From the nervous system: rarely: dizziness, headache, ataxia,

disorientation, muscle weakness.

From the hematopoiesis: rarely: leukopenia.

From the side of the urinary system: interstitial nephritis, nephronecrosis.

Other: induction of porphyria, disorders of the menstrual cycle, myasthenia gravis, hyperuricemia, exacerbation of gout.

Local reactions: phlebitis at the site of administration.

With intermittent or irregular therapy, or with the resumption of treatment after an interruption, 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 indicated in the instruction are aggravated, or you notice any other side effects not specified in the instructions, inform the doctor about it.

Overdose:Symptoms: pulmonary edema, confusion, convulsions.

Treatment: symptomatic; forced diuresis.

Interaction:

Rifampicin induces the induction of the enzyme system of the liver of the cytochrome P-450 system, accelerating the metabolism of drugs. Rifampicin accelerates the metabolism (the concentration in the blood plasma decreases and, accordingly, the effect decreases: antiarrhythmic agents (disopyramide, pyrmenol, quinidine, mexiletine, tokainid), theophylline, some tricyclic antidepressants, oral hypoglycemic drugs, indirect anticoagulants, azathioprine, barbiturates (phenobarbital, hexobarbital, etc.), buspirone, blockers of "slow" calcium channels (diltiazem, nifedipine, verapamil), antifungal drugs (intraconazole, etc.), cimetidine, thyroxine, glucocorticosteroids, carbamazepine, hydantoins (phenytoin), zidovudine, dapsone, chloramphenicol, terbinafine, neuroleptics (haloperidol and others), tranquilizers (diazepam and others), beta-blockers (propranolol and others), cardiac glycosides, (digoxin and others), propafenone, cyclosporine, sex hormones, enalapril, cyclooxygenase-2 inhibitors (celecoxib , etc.), hypolipidemic drugs (simvastatin and others), losartan, antimalarial drugs (mefloquine and others), cytostatics (tamoxifen and etc.). Joint use should be avoided with HIV protease inhibitors (indinavir, nelfinavir). Rifampicin accelerates the metabolism of estrogens and gestagens (the effect of oral contraceptives decreases).

Isoniazid and / or pyrizinamide increases the frequency and severity of liver function disorders more than with the administration of a single rifampicin in patients with a previous liver disease. Co-trimoxazole (sulfamethoxazole / trimethoprim) increases the concentration of rifampicin in the blood.

Special instructions:

Treatment with rifampicin should be done under close medical supervision. Intravenous infusion is carried out under the control of arterial pressure, with prolonged administration, the development of phlebitis is possible.

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

Treatment with the drug should begin after a study of liver function (determination of the concentration of bilirubin, and the activity of aminotransferases in the blood, thymol assay), and in the process of treatment, conduct it on a monthly basis. With increasing phenomena of liver function disorder, the use of the drug should be discontinued.

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

To prevent the development of resistance, microorganisms must be used in combination with other antimicrobial drugs. In the case of a flu-like syndrome, not complicated by thrombocytopenia, hemolytic anemia, bronchospasm, dyspnea, shock, and renal failure in patients receiving medication for intermittent scheme, you should consider switching to a daily intake.In these cases, the dose is increased slowly on the first day prescribe 75-150 mg, and the desired therapeutic dose is achieved in 3-4 days. In the event that the above serious complications persist, rifampicin cancel. It is necessary to monitor kidney function; an additional prescription of glucocorticosteroids is possible.

Therapy during pregnancy (especially in the first trimester) is possible only by "vital" indications. When appointing in the last weeks of pregnancy, postpartum bleeding in the mother and bleeding in the newborn can be observed, in this case vitamin K is prescribed. Women of reproductive age should be treated with reliable contraceptive methods (oral hormonal contraceptives and additional non-hormonal methods of contraception).

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

During the treatment period, it is impossible to apply microbiological methods for determining the concentration of folic acid and vitamin B12 in the blood serum.A false-positive result is possible in the immunological determination of opiates in the blood. It should be borne in mind that rifampicin interacts with contrast preparations used in cholecystography. Under its influence, the results of X-ray diffraction can be distorted.

During the treatment period, to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

After the expiry date of the drug, unused vials should be carefully opened, the contents dissolved in a large amount of water and drained into the drain.

Form release / dosage:

Lyophilizate for the preparation of a solution for infusions of 150 mg, 300 mg, 450 mg, 600 mg of active substance /

Packaging:

Liofilizate for the preparation of a solution for infusions of 150 mg, 300 mg, 450 mg, 600 mg of active substance in bottles with the capacity of 10 ml, 20 ml, 30 ml. 1 or 10 bottles with instructions for use in a cardboard box. For hospitals:

- 50 bottles with an equal number of instructions for use in a cardboard box;

- from 1 to 50 bottles with an equal number of instructions for use in a cardboard box.

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

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002304

Date of registration:14.11.2013/02.04.2014

Date of cancellation:2018-11-14

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp13.05.2016

Illustrated instructions

Instructions

Rifampicin (Rifampicin)