Isoniazid + Rifampicin + [Pyridoxine] - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Other synthetic antibacterial agents

Included in the formulation

Protub®-2

pills inwards

FARMASINTEZ, JSC (Irkutsk) Russia

Rifakomb

pills inwards

Ipka Laboratories Ltd. India

Tubavit

pills inwards

VALENTA PHARM, PAO Russia

АТХ:

J.04.A.M.02 Isoniazid in combination with rifampicin

Pharmacodynamics:

Combined anti-tuberculosis drug.

Isoniazid

Inhibits the enzymes necessary for the synthesis of mycolic acids, which are the main structural fragments of the cell walls of mycobacterium tuberculosis.

The most intensive synthesis of mycolic acids is carried out in growing cells, so isoniazid has a bactericidal action on them, and bacteriostatic action on mature cells.

The high selectivity of the chemotherapeutic effect of isoniazid is due to the fact that there are no mycolic acids in the tissues of the macroorganism, as well as in other microorganisms.

Rifampicin

Semisynthetic antibacterial agent of bactericidal action. Selectively inhibits the DNA-dependent RNA polymerase of mycobacterium tuberculosis and leprosy.

Pyridoxine

Vitamin B₆. In the body, phosphorylation is converted to pyridoxal-5-phosphate, which is part of the enzymes involved in decarboxylation, transamination and racemization of amino acids.Prevents the development of peripheral polyneuropathy, which develops due to the impact of anti-tuberculosis drugs.

Pharmacokinetics:

Isoniazid

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration in blood plasma is achieved in 1-4 hours. The connection with plasma proteins is from 1 to 10%.

Therapeutic effect develops after the reception. Metabolism in the liver by acetylation to inactive metabolites, penetrates the placental barrier, is excreted in breast milk.

The rate of acetylation of the drug is genetically determined, so the half-life of isoniazid varies. Half-life for "fast acetylators" is 1 hour, for "slow acetylators" - 3 hours. Elimination by the kidneys.

Rifampicin

After oral administration, up to 98% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved in 2-3 hours. The connection with plasma proteins is 84-91%.

Metabolism in the liver. Penetrates through blood-brain and placental barriers, excreted in breast milk.

The half-life is 2.5-5 hours. Elimination with feces and kidneys.

Pyridoxine

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 2 hours. The connection with plasma proteins is 90%.

Metabolism in the liver. Penetrates through the placenta, found in breast milk.

The half-life is 15-20 days. Elimination by the kidneys. It is deduced by hemodialysis.

Indications:

It is used to treat tuberculosis of any location. Used for leprosy, bronchitis, pneumonia, osteomyelitis, gonorrhea, infections of the biliary and urinary tract.

ICD-10

I.A15-A19.A15 Tuberculosis of respiratory organs, confirmed bacteriologically and histologically

I.A30-A49.A30 Leprosy [Hansen's disease]

I.A50-A64.A54 Gonococcal infection

X.J00-J06.J00 Acute nasopharyngitis (runny nose)

X.J00-J06.J01 Acute Sinusitis

X.J00-J06.J02 Acute pharyngitis

X.J00-J06.J03 Acute tonsillitis

X.J00-J06.J04 Acute laryngitis and tracheitis

X.J10-J18.J15 Bacterial pneumonia, not elsewhere classified

X.J20-J22.J20 Acute bronchitis

X.J30-J39.J31 Chronic rhinitis, nasopharyngitis and pharyngitis

X.J30-J39.J32 Chronic Sinusitis

X.J30-J39.J37 Chronic laryngitis and laryngotracheitis

X.J40-J47.J42 Chronic bronchitis, unspecified

XI.K80-K87.K81.0 Acute cholecystitis

XI.K80-K87.K81.1 Chronic cholecystitis

XI.K80-K87.K83.0 Cholangitis

XIII.M00-M03.M00 Pyogenic arthritis

XIII.M86-M90.M86 Osteomyelitis

XIV.N10-N16.N11 Chronic tubulointerstitial nephritis

XIV.N10-N16.N10 Acute tubulointerstitial nephritis

XIV.N30-N39.N30 Cystitis

XIV.N30-N39.N34 Urethritis and urethral syndrome

XIV.N40-N51.N41 Inflammatory diseases of the prostate

Contraindications:

Children under 1 year old, jaundice, pregnancy (I trimester) and lactation, individual intolerance.

Carefully:

II-III trimester of pregnancy, renal and hepatic insufficiency, diabetes mellitus.

Pregnancy and lactation:

Recommendations for FDA - Category C. It is used with caution in the II-III trimester of pregnancy, when the expected effect of treatment exceeds the risk for the fetus.

Dosing and Administration:

Inside, before meals once a day, depending on the body weight:

less than 40 kg - 3 tablets each;

40-49 kg - 4 tablets each;

50-69 kg - 5 tablets each;

over 70 kg - 6 tablets each.

The highest daily dose: 6 tablets.

The highest single dose: 6 tablets.

Side effects:

Isoniazid

Central and peripheral nervous system: memory disorders, insomnia, mental disorders disorders, euphoria, peripheral neuritis, muscle twitching.

The cardiovascular system: pain in the heart.

Digestive system: medicinal hepatitis.

Dermatological reactions: itching, skin rash.

Sense organs: optic neuritis - blurred vision or loss of vision.

Reproductive system: gynecomastia, menorrhagia.

Allergic reactions.

Rifampicin

Central and peripheral nervous system: headache, disorientation, hallucinations.

Respiratory system: bronchospasm.

Hemopoietic system: eosinophilia.

Digestive system: nausea, vomiting, decreased appetite, diarrhea, hepatitis, enterocolitis.

Dermatological reactions: a rash.

Sense organs: impaired vision.

Allergic reactions.

Pyridoxine

Central and peripheral nervous system: a feeling of constriction and compression of the distal parts of the limbs - a symptom of "gloves" and "stocking."

Digestive system: heartburn.

Allergic reactions.

Overdose:

Metabolic acidosis, neurotoxic effect: dysarthria, lethargy, disorientation, hyperreflexia, convulsions, coma.

Treatment is symptomatic. Effective hemodialysis.

Interaction:

Strengthens the action indirect hemocoagulants.

Inhibits the metabolism of benzodiazepines, phenytoin and theophylline.

Simultaneous use with paracetamol and other hepatotoxic substances increases the risk of toxic hepatonecrosis.

Antatsidnye means slow down and reduce the absorption of isoniazid in the intestine, it is recommended to take them with an interval of 1 hour.

With the simultaneous use of certain fish species (tuna, sardinella) and cheeses (Swiss), there may be a hyperemia of the skin, itching, headache due to the isoniazid suppression of monoamine oxidase and diaminoxidase activity in the blood plasma and a violation of the metabolism of histamine and tyramine.

Rifampicin reduces the effects of anticoagulants, hormonal contraceptives, antiarrhythmics, ketoconazole, cyclosporine, phenytoin, chloramphenicol, glucocorticosteroids, enalapril, slow calcium channel blockers, cimetidine.

Opiates, antacids, ketoconazole reduce the bioavailability of rifampicin.

Special instructions:

It is recommended to use reliable contraceptive methods during taking the drug.

In the treatment it is not recommended to drive vehicles and work with moving mechanisms.

Instructions

Isoniazid + Rifampicin + [Pyridoxine] (Isoniazidum + Rifampicinum + [Pyridoxinum])