Eremfat (Tablets, Lyophilisate) Instructions for Use

ATC Code

J04AB02 (Rifampicin)

Active Substance

Rifampicin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic of the rifamycin group. Antituberculosis drug

Pharmacotherapeutic Group

Antibiotic-rifamycin

Pharmacological Action

[I] – Instructions for medical use approved by the Pharmacological Committee of the Ministry of Health of the Russian Federation

A broad-spectrum semisynthetic antibiotic, a first-line antituberculosis agent.

In low concentrations, it exerts 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-producing and many methicillin-resistant strains), Streptococcus spp., Clostridium spp., Bacillus anthracis; gram-negative cocci: meningococci, gonococci.

It acts on gram-positive bacteria in high concentrations. It is active against both intracellularly and extracellularly located microorganisms.

It selectively inhibits DNA-dependent RNA polymerase of susceptible microorganisms. With monotherapy, selection of rifampicin-resistant bacteria occurs relatively quickly.

Cross-resistance with other antibiotics (except for other rifamycins) does not develop.

Pharmacokinetics

Rapidly distributed to organs and tissues (the highest concentration in the liver and kidneys), penetrates into bone tissue, concentration in saliva is 20% of plasma concentration.

V_d is 1.6 L/kg in adults and 1.1 L/kg in children. Plasma protein binding is 84-91%.

It penetrates the blood-brain barrier only in case of meningeal inflammation. It crosses the placenta (concentration in fetal plasma is 33% of the concentration in maternal plasma) and is excreted in breast milk (breastfed 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-desacetylrifampicin. It is an autoinducer – it accelerates its own metabolism in the liver, resulting in a creatinine clearance of 6 L/h after the first dose, increasing to 9 L/h after repeated administration.

When taken orally, induction of intestinal wall enzymes is also likely. T_1/2 of the drug after oral administration of 300 mg is 2.5 hours, 600 mg is 3-4 hours, 900 mg is 5 hours.

After several days of repeated administration, bioavailability decreases, and T_1/2 after multiple doses of 600 mg shortens to 1-2 hours.

It is excreted mainly with bile, 80% as a metabolite; by the kidneys – 20%. After administration of 150-900 mg of the drug, the amount of rifampicin excreted by the kidneys unchanged depends on the dose taken and is 4-20%.

In patients with impaired renal excretory function, T_1/2 is prolonged only when its doses exceed 600 mg. It is removed by peritoneal dialysis and hemodialysis. In patients with impaired liver function, an increase in the plasma concentration of rifampicin and a prolongation of T_1/2 are noted.

Indications

• Tuberculosis of all forms and localizations as part of combination therapy;
• Leprosy (in combination with dapsone and clofazimine – multibacillary types of the disease);
• Infectious diseases caused by susceptible microorganisms (in cases of resistance to other antibiotics and as part of combined antimicrobial therapy; after excluding the diagnosis of tuberculosis and leprosy);
• Brucellosis – as part of combination therapy with an antibiotic of the tetracycline group (doxycycline);
• Meningococcal meningitis (prevention in persons who have been in close contact with patients with meningococcal meningitis; in carriers of Neisseria meningitidis).

ICD codes

Dosage Regimen

Lyophilisate

Parenterally – IV drip. IV – for acutely progressive and widespread 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 at the site of infection, in cases where oral administration of the drug is difficult or poorly tolerated by patients.

For IV administration, the daily dose for adults is 450 mg, for severe, rapidly progressive forms – 600 mg, administered in one dose.

The duration of IV administration depends on tolerance and is 1 month or more (with 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 infections of non-tuberculous etiology, the daily dose is 300-900 mg (maximum – 1.2 g). The daily dose is divided into 2-3 administrations.

The duration of treatment is set individually, depends on effectiveness and can be 7-10 days. IV administration should be discontinued as soon as oral administration becomes possible.

To prepare a solution for IV administration, every 150 mg is 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 infusion rate is 60-80 drops/min.

Preparation of solution for IV infusion: dilute the lyophilized powder by adding 10 ml of sterile water for injection to the vial with the drug. Shake the vial to ensure complete dissolution of the vial contents.

For treatment of tuberculosis, it is combined with at least one other antituberculosis drug (isoniazid, pyrazinamide, ethambutol, streptomycin). Adults weighing less than 50 kg – 450 mg/day; 50 kg and more – 600 mg/day. Children and newborns – 10-20 mg/kg/day; maximum daily dose – 600 mg.

For tuberculous meningitis, disseminated tuberculosis, spinal involvement with neurological manifestations, in 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 case of pulmonary tuberculosis and detection of mycobacteria in sputum, the following 3 regimens are used (all lasting 6 months)

1. First 2 months – as above; 4 months – daily, in combination with isoniazid.
2. First 2 months – as above; 4 months – in combination with isoniazid, 2-3 times per week.
3. Throughout the course – administration in combination with isoniazid, pyrazinamide and ethambutol (or streptomycin) 3 times per week. In cases where antituberculosis drugs are used 2-3 times a week (as well as in case of exacerbations of the disease or ineffectiveness of therapy), their administration should be carried out under the supervision of medical personnel.

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

For the treatment of multibacillary types of leprosy (tuberculoid and borderline tuberculoid)adults – 600 mg once a month, in combination with dapsone – 100 mg (1-2 mg/kg) once/day; children – 10 mg/kg once a month, in combination with dapsone – 1-2 mg/kg/day.

Duration of treatment is 6 months.

For the treatment of infectious diseases caused by susceptible microorganisms, it is prescribed in combination with other antimicrobial agents. The daily dose for adults is 0.6-1.2 g, for children and newborns – 10-20 mg/kg. Frequency of administration – 2 times/day.

For the treatment of brucellosis – 900 mg/day once in combination with doxycycline; average duration of treatment is 45 days.

For the prevention of meningococcal meningitis – 2 times/day every 12 hours for 2 days. Single doses for adults – 600 mg; for children – 10 mg/kg; for newborns – 5 mg/kg.

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

Tablets

Orally, on an empty stomach, 30 minutes before meals. For treatment of tuberculosis, it is combined with at least one other antituberculosis drug (isoniazid, pyrazinamide, ethambutol, streptomycin). Adults weighing less than 50 kg – 450 mg/day; 50 kg and more – 600 mg/day. Children and newborns – 10-20 mg/kg/day; maximum daily dose – 600 mg.

For tuberculous meningitis, disseminated tuberculosis, spinal involvement with neurological manifestations, in 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 case of pulmonary tuberculosis and detection of mycobacteria in sputum, the following 3 regimens are used (all lasting 6 months)

1. First 2 months – as above; 4 months – daily, in combination with isoniazid.
2. First 2 months – as above; 4 months – in combination with isoniazid, 2-3 times per week.
3. Throughout the course – administration in combination with isoniazid, pyrazinamide and ethambutol (or streptomycin) 3 times per week. In cases where antituberculosis drugs are used 2-3 times a week (as well as in case of exacerbations of the disease or ineffectiveness of therapy), their administration should be carried out under the supervision of medical personnel.

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

For the treatment of multibacillary types of leprosy (tuberculoid and borderline tuberculoid)adults – 600 mg once a month, in combination with dapsone – 100 mg (1-2 mg/kg) once/day; children – 10 mg/kg once a month, in combination with dapsone – 1-2 mg/kg/day.

Duration of treatment is 6 months.

For the treatment of infectious diseases caused by susceptible microorganisms, it is prescribed in combination with other antimicrobial agents. The daily dose for adults is 0.6-1.2 g, for children and newborns – 10-20 mg/kg. Frequency of administration – 2 times/day.

For the treatment of brucellosis – 900 mg/day once in combination with doxycycline; average duration of treatment is 45 days.

For the prevention of meningococcal meningitis – 2 times/day every 12 hours for 2 days. Single doses for adults – 600 mg; for children – 10 mg/kg; for newborns – 5 mg/kg.

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

Adverse Reactions

Nausea, vomiting, diarrhea, anorexia, erosive gastritis, pseudomembranous enterocolitis; increased activity of liver transaminases in blood serum, hyperbilirubinemia; allergic reactions (urticaria, eosinophilia, angioedema, bronchospasm, arthralgia, fever); leukopenia, dysmenorrhea, headache, hepatitis; induction of porphyria; interstitial nephritis, decreased visual acuity, ataxia, disorientation, muscle weakness. 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.

Contraindications

• Hypersensitivity;
• Jaundice;
• Recently (less than 1 year) suffered infectious hepatitis;
• Pregnancy (only for vital indications);
• Lactation period;
• Chronic renal failure;
• Pulmonary-heart failure stage II-III;
• Infancy.

Use in Pregnancy and Lactation

The use of the drug during pregnancy (only for vital indications) and during lactation is contraindicated.

Therapy during pregnancy (especially in the first trimester) is possible only for vital indications. When prescribed in the last weeks of pregnancy, postpartum bleeding in the mother and bleeding in the newborn may be observed. In this case, vitamin K is prescribed.

Women of childbearing age during treatment should use reliable methods of contraception (oral hormonal contraceptives and additional non-hormonal methods of contraception).

Use in Hepatic Impairment

In patients with impaired liver function, an increase in the plasma concentration of rifampicin and a prolongation of T_1/2 are noted.

Use in Renal Impairment

In patients with impaired renal excretory function, T_1/2 is prolonged only when its doses exceed 600 mg.

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

Use in chronic renal failure is contraindicated.

Pediatric Use

The drug is contraindicated in infants.

Special Precautions

During treatment, skin, sputum, sweat, feces, tear fluid, and urine acquire an orange-red color. It may permanently stain soft contact lenses.

To prevent the development of microbial resistance, it must be used in combination with other antimicrobial agents.

In case of development of flu-like syndrome, not complicated by thrombocytopenia, hemolytic anemia, bronchospasm, shortness of breath, shock and renal failure, in patients receiving the drug on an intermittent regimen, the possibility of switching to daily administration should be considered. In these cases, the dose is increased slowly: on the first day, 75-150 mg is prescribed, and the required therapeutic dose is reached in 3-4 days. In case of the above serious complications, Rifampicin should be discontinued. Kidney function should be monitored; additional administration of glucocorticosteroids is possible.

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

With long-term use, systematic monitoring of the peripheral blood picture and liver function is indicated. During treatment, microbiological methods for determining the concentration of folic acid and vitamin B₁₂ in blood serum should not be used.

Overdose

Symptoms pulmonary edema, confusion, convulsions.

Treatment gastric lavage, administration of activated charcoal; symptomatic therapy, forced diuresis.

Drug Interactions

Antacids, opiates, anticholinergic agents and ketoconazole reduce (in case of simultaneous oral administration) the bioavailability of rifampicin. Isoniazid and/or pyrazinamide increase the frequency and severity of liver function disorders to a greater extent than when prescribing rifampicin alone, in patients with pre-existing liver disease. PAS preparations containing bentonite (aluminum hydrosilicate) should be prescribed no earlier than 4 hours after taking the drug, because absorption may be impaired.

It reduces the activity of oral anticoagulants, oral hypoglycemic drugs, hormonal contraceptives, digitalis preparations, antiarrhythmic agents (disopyramide, pirmenol, quinidine, mexiletine, tocainide), glucocorticosteroids, dapsone, hydantoins (phenytoin), hexobarbital, nortriptyline, benzodiazepines, sex hormones, theophylline, chloramphenicol, ketoconazole, itraconazole, cyclosporine A, azathioprine, beta-blockers, slow calcium channel blockers, enalapril, cimetidine (Rifampicin induces the liver enzyme system of the cytochrome P450 system, accelerating the metabolism of drugs).

Storage Conditions

List B.

Store in a dry, light-protected place, out of reach of children, at a temperature not exceeding 25°C (77°F).

Opened packages with the drug dissolved in aseptic conditions with water for injection can be stored at room temperature for 4 hours. After this time, the infusion solution must be used immediately for continuous IV drip infusion.

Shelf Life

Shelf life – 2 years.

The drug should not be used after the expiration date indicated on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.