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

active substance: rifampicin sodium - 462.2 mg (corresponding to 450 mg of rifampicin) and Excipients: sodium ascorbate-51.3 mg, sodium sulfite-9 mg

1 bottle of lyophilizate for the preparation of a solution for infusions 600 mg contains

active substance: rifampicin sodium - 616.2 mg (corresponding to 600 mg of rifampicin) and Excipients: sodium ascorbate - 68.4 mg, sodium sulfite - 12 mg

Description:Porous mass or a mixture of porous mass and powder of brick or brownish-red color, marble color is allowed.

Pharmacotherapeutic group:Antibiotic-rifamycin.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.02 Rifampicin

Pharmacodynamics:Semisynthetic broad-spectrum antibiotic, antituberculous drug of the 1st series. At low concentrations, it has a bactericidal effect on Mycobacterium tyberculosis, Brucella spp., Chlamydia trachomatis, Legionella pneumophila, Rickettsia typhi, Mycobacterium leprae; in high concentrations - on some gram-negative organisms.Characterized by high activity against Staphylococcus spp. (including penicillinase-forming and many strains of methicillin-resistant), Streptococcus spp., Clostridium spp., Bacillus antracis; Gram-negative cocci: meningococci, gonococci. Gram-positive bacteria acts in high concentrations. It is active with respect to intracellular and extracellularly located microorganisms. Suppresses the DNA-dependent RNA polymerase of microorganisms. When the drug is monotherapy, the selection of rifampicin-resistant bacteria is observed relatively quickly. Cross-resistance with other antibiotics (with the exception of the other rifamycins) does not develop.

Pharmacokinetics:

With intravenous administration, the therapeutic concentration is maintained for 8-12 hours. Communication with blood plasma proteins - 84-91%.

Quickly distributed to organs and tissues (the highest concentration - in the liver and kidneys), penetrates into the bone tissue, concentration in the saliva - 20% of the plasma. The apparent volume of distribution is 1.6 l / kg in adults and 1.1 l / kg in children.

Through the blood-brain barrier penetrates only in case of inflammation of the meninges. Penetrates through the placenta (concentration in the plasmafetal blood - 33% of the concentration in the blood plasma of the mother) 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%. After taking 150-900 mg of the drug, the amount of rifampicin excreted by the kidneys in an unchanged form depends on the value of the dose taken and is 4-20%.

In patients with impaired renal excretory function, the elimination half-life is prolonged only when the dose of rifampicin exceeds 600 mg. It is excreted in peritoneal dialysis and hemodialysis. In patients with impaired hepatic function, an increase in the concentration of rifampicin in the blood plasma and an increase in the half-life.

Indications:

Tuberculosis (all forms) - as part of combination therapy. Leprosy (in combination with dapsone - multibacillary types of the disease).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 antibiotics of the tetracycline group (doxycycline).

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

Contraindications:Hypersensitivity to the components of the drug, jaundice, recently transferred (less than 1 year) infectious hepatitis, chronic renal failure, severe pulmonary heart failure, breast age.

Pregnancy and lactation:

Therapy during pregnancy (especially in I trimester) is possible only for health reasons. In the appointment of the last weeks of pregnancy may experience post-partum haemorrhage in the mother and the newborn bleeding. In this case, prescribe vitamin K.

The drug is contraindicated during lactation.

Dosing and Administration:

Rifampicin is administered parenterally - intravenously drip.The rate of administration is 60-80 drops per minute.

Intravenous administration of the drug is recommended for the acute and progressive forms of destructive pulmonary tuberculosis, severe purulent-septic processes, when it is necessary to quickly create high concentrations of the drug in the blood and in the focus of infection, in cases where the drug is difficult to take or poorly tolerated by patients.

Preparation of solutions for intravenous infusion

For a dosage of 300 mg:

dilute the lyophilizate, adding 5 ml of water for injection into the vial with the drug, shake the vial to ensure complete dissolution of the contents of the vial. The resulting solution is mixed with 250 ml of a 5% solution of dextrose.

For a dosage of 450 mg:

dilute the lyophilizate, adding 7.5 ml of water for injection into the vial with the drug, shake the vial to ensure complete dissolution of the contents of the vial. The resulting solution is mixed with 375 ml of a 5% dextrose solution

For a dosage of 600 mg:

dilute the lyophilizate by adding 10 ml of water for injection into the vial with the drug, shake the vial to ensure complete dissolution of the contents of the vial. The resulting solution is mixed with 500 ml of a 5% dextrose solution

During the dissolution of the preparation in water for injection, a large number of vesicles are formed, which disappear when the preparation is completely dissolved. The contents of the vial completely dissolve within 5 minutes.

If a smaller dose of rifampicin is needed, the required number of milliliters of vials of the dissolved preparation (10 ml = 600 ml of rifampicin, 7.5 ml = 450 mg, 5 ml = 300 mg of rifampicin, etc.) and mixed with 5% solution dextrose. For intravenous administration, the daily dose for adults - 450 mg, in severe, rapidly progressive forms - 600 mg, administered in one portion. The duration of intravenous administration depends on the tolerability of the drug and is 1 month or more (with a subsequent transition to oral administration). The total duration of use for tuberculosis is determined by the effectiveness of treatment and can reach 1 year.

With infections of non-tuberculous etiology, the daily dose of Rifampicin is 0.3-0.9 g (maximum - 1.2 g). 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 tuberculosis rifampicin combined with at least one antituberculous 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. Children and newborns - 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 and ethambutol (or streptomycin), 7 months - in combination with isoniazid.

In the case of pulmonary tuberculosis and detection of mycobacteria in sputum, one of the following 3 regimens (all of 6 months) is used:

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

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

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

For treatment of multibacillary types of leprosy (lepromatous, borderline, lepromatous and borderline) adults - 600 mg once a month in combination with dapsone (100 mg once a day) and clofazimine (50 mg once a day + 300 mg once a month ); children - 10 mg / kg

1 once a month in combination with dapsone (1-2 mg / kg / day) and clofazimine (50 mg every other day + 200 mg once a month). The minimum duration of treatment is 2 years.

To treat pausibacillary types of leprosy (tuberculoid and border tuberculoid) adults - 600 mg once a month, in combination with dapsone - 100 mg (1-2 mg / kg) once a day; children - 10 mg / kg once a month, in combination with dapsone - 1-2 mg / kg / day. Duration of treatment - 6 months.

To treat infectious diseases caused by sensitive microorganisms, it is prescribed in combination with other antimicrobial drugs. The daily intake for adults is 0.6-1.2 g; for children and newborns - 10-12 mg / kg. Multiplicity of admission - 2 times a day.

For 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 - 10 mg / kg; for newborns - 5 mg / kg.

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

Side effects:Side effects are presented with the following assessment of the frequency of development: very frequent -1/10 appointments (>10%;) Frequent - 1/100 appointments (>1% and <10%); not frequent - 1/1000 appointments (>0.1% and <1%); rare - 1/10000 prescriptions (>0.01% and <0.1%); very rare - 1/10000 prescriptions (<0.01%).

From the side of the digestive system, often - loss of appetite, abdominal pain, nausea, vomiting, flatulence and diarrhea; rarely acute pancreatitis; very rarely - pseudomembranous colitis.

From the liver and biliary tract: often or very often - increased activity of "liver" transaminases, alkaline phosphatase, gamma-glutamylpeptidase, less often bilirubin; in very rare cases (especially in patients with existing violations of liver function, alcoholism, the elderly,with simultaneous administration of other hepatotoxic anti-tuberculosis drugs): jaundice and hepatomegaly, which in most cases are transient.

On the part of the blood system: rarely - eosinophilia, leukopenia, granulocytopenia, thrombocytopenia, thrombocytopenic purpura, hypoprothrombinemia and hemolytic anemia; very rarely disseminated coagulopathy.

From the immune system: often - reactions of hypersensitivity (fever, exudative erythema multiforme, exanthema nosopodobnaya erythema, pruritis, urticaria); rarely - lupus-like symptoms such as fever, weakness, pain in muscles and ligaments, the appearance of antinuclear antibodies; very rarely (with combined therapy): severe allergic reactions from the skin, such as necrolysis epidermal toxic (Lyell's syndrome), exfoliative dermatitis, ordinary pemphigus; rarely - shallow breathing, asthma-like reactions, pulmonary edema and shock. Grippopodobny syndrome (only with the intermittent treatment regimen or with irregular use of rifampicin, the more often,the longer the intervals between application of the drug): fever, chills, exanthema, nausea, vomiting, pain in the muscles and joints, headache and weakness. It develops 3-6 months after the initiation of therapy in the intermittent mode. Symptoms appear 1-2 hours after the drug is administered and last up to 8 hours, and in some cases even longer. In almost all cases, the flu-like syndrome occurs when intermittent treatment is replaced with daily rifampicin. At the same time, the daily dose of the drug is gradually increased from 50-150 mg on the first day to 50-150 mg per day until the required dose is reached. You can use corticosteroids.

On the part of the endocrine system, rarely - violation of menstruation.

From the side of the nervous system, rarely - myopathy; very rarely - headache, ataxia, impaired concentration, increased fatigue, muscle weakness, pain in the limbs, numbness.

From the side of the organ of vision: rarely - deterioration of vision, loss of vision, optic neuritis.

On the part of the respiratory system, very rarely - acute respiratory distress syndrome and pneumonitis.

From the urinary system: very rarely - acute renal failure, nephronecrosis, interstitial nephritis.

From the skin: very rarely - a burning sensation of the skin.

Overdose:

Symptoms: pulmonary edema, lethargy, confusion, convulsions.

Treatment: symptomatic; gastric lavage, Activated carbon; forced diuresis.

Interaction:Reduces the activity of oral anticoagulants, oral hypoglycemic drugs, hormone contraceptives, digitalis drugs, antiarrhythmic drugs (disopyramide, pirmenol, quinidine, mexiletine, tokainid), glucocorticosteroids, dapsone, phenytoin, hexobarbital, nortriptyline, benzodiazepines, sex hormones, theophylline, chloramphenicol, ketoconazole, itraconazole, cyclosporine A, azathioprine, beta adrenoblockers, slow calcium channel blockers, enalapril, cimetidinerifampicin causes the induction of certain enzyme systems of the liver, accelerates metabolism). Antacids, opiates, anticholinergic drugs and ketoconazole reduce (in the case of simultaneous ingestion) bioavailability of rifampicin. Isoniazid and / or pyrazinamide increase the frequency and severity of liver function disorders to a greater extent than with the appointment of a single rifampicin, in patients with a previous liver disease. Paraaminosalicylic acid preparations containing bentonite (aluminum hydrosilicate) should be administered no earlier than 4 hours after taking the drug, since absorption impairment is possible.

Special instructions:

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

Intravenous infusion is carried out under the control of arterial pressure, with prolonged administration, the development of phlebitis is possible.

To prevent the development of resistance of microorganisms, it is necessary to use the drug 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 are noted, rifampicin cancel. It is necessary to monitor kidney function; possibly additional appointment of glucocorticosteroids.

Women of reproductive age during treatment should use reliable methods of contraception (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.

With prolonged use, a systematic control of the peripheral blood picture and liver function is shown. During the treatment period, it is impossible to apply microbiological methods for determining folic acid and vitamin B12 in the blood serum.

Effect on the ability to drive transp. cf. and fur:Data confirming the effect of rifampicin on the ability to engage in potentially hazardous activities that require increased attention, no.

Form release / dosage:Lyophilizate for the preparation of a solution for infusions 300 mg, 450 mg 600 mg.

Packaging:For 300 mg, 450 mg of rifampicin in bottles of neutral glass grade HC-3 with a capacity of 10 ml or 20 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps or caps with aluminum combined or imported combination caps with plastic disks. For 600 mg of rifampicin in bottles of neutral glass grade NS-3 with a capacity of 20 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps or caps with aluminum combined or imported combination caps with plastic disks. 1 bottle with instructions for use in a pack of cardboard. 5 bottles in a contour plastic packaging (pallet) or in a planar cell package. 1, 2 contour plastic packages (pallets) or contour mesh packages together with instructions for use in a pack of cardboard. 10 vials together with instructions for use in a pack or box with a liner for fixing vials of cardboard.

10, 25 bottles together with instructions for use in the box. Vials are separated between the rows by cardboard pads.

Packing for hospitals

10, 20 contour plastic packages (pallets) or contour mesh packages together with an equal number of instructions for use in a cardboard box. 25, 50, 100 bottles together with an equal number of instructions for use in a cardboard box. Vials are separated between the rows by cardboard pads.

Storage conditions:In dry, 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001924

Date of registration:06.12.2012/02.02.2016

Date of cancellation:2017-12-06

The owner of the registration certificate:BINERGIYA, CJSC BINERGIYA, CJSC Russia

Manufacturer: & nbsp

RAFARMA, JSC Russia

Information update date: & nbsp14.05.2016

Illustrated instructions

Instructions

Rifampicin-Binergic (Rifampicin-Binergia)