Isocomb
Isocomb: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Isocomb
ATX code: J04AM06
Active ingredient: Isoniazid + Pyrazinamide + Rifampicin + Ethambutol + Pyridoxine (Isoniazid + Pyrazinamide + Rifampicin + Ethambutol + Pyridoxine)
Manufacturer: M. J. Biopharm Pvt. Ltd. (MJ Biopharm, Pvt. Ltd.) (India)
Description and photo updated: 2019-30-05
Isocomb is a combined anti-tuberculosis drug.
Release form and composition
The drug is available in the form of coated tablets: biconvex, oval, dark brown, a reddish-brown core with white splashes is visible in the cut (50 pcs. Or 100 pcs. In polypropylene or polyethylene cans, one can in a cardboard box and instructions for use of Isocomb; for hospitals - in cardboard boxes 25 cans of 100 tablets each or in bags of non-stabilized polyethylene film of 500 or 1000 tablets, 1 bag in a polypropylene or polyethylene container).
Composition for 1 tablet:
- active ingredients: ethambutol hydrochloride - 225 mg, rifampicin - 120 mg, isoniazid - 60 mg, pyrazinamide - 300 mg, pyridoxine hydrochloride - 20 mg;
- auxiliary components: microcrystalline cellulose, colloidal silicon dioxide, talc, corn starch, sodium starch glycolate, croscarmellose sodium, magnesium stearate;
- film casing: Opadry brown 04В56936.
Pharmacological properties
Pharmacodynamics
Isocomb is a five-component drug that contains a fixed amount of ethambutol, rifampicin, isoniazid, pyrazinamide and pyridoxine hydrochloride.
Pharmacological properties of individual components of Isocomb:
- ethambutol: is a bacteriostatic agent effective against mycobacterium tuberculosis, which are resistant to other anti-tuberculosis drugs. The mechanism of action of ethambutol is associated with the suppression of cell wall synthesis by blocking the process of inclusion of mycolic acids into it. The drug is active against slow and fast growing atypical mycobacteria. The minimum inhibitory concentration of ethambutol is from 0.78 to 2 mg / l;
- rifampicin: inhibits DNA-dependent RNA polymerase, has a bactericidal effect on microorganisms located inside and outside cells. The minimum inhibitory concentration of rifampicin for Mycobacterium tuberculosis is 2 mg / l;
- isoniazid: affects actively dividing cells of Mycobacterium tuberculosis, inhibits the synthesis of mycolic acids, which are one of the components of the cell walls of mycobacteria. The minimum inhibitory concentration of isoniazid for tuberculous mycobacteria is from 0.025 to 0.05 mg / l. It has a moderate effect on slow-growing and fast-growing atypical mycobacteria;
- pyrazinamide: affects the type I mycobacterial fatty acid synthase gene, which is involved in the biosynthesis of mycolic acid. It acts on mycobacteria located inside cells, and also penetrates well into tuberculous foci. In an acidic environment, pyrazinamide is more effective. In the human body, under the influence of enzymes, it turns into pyrazinic acid, which is its active form and exhibits bactericidal properties. The minimum inhibitory concentration of pyrazinamide at acidic pH is 20 mg / l;
- pyridoxine hydrochloride: one of the forms of water-soluble vitamin B 6 involved in metabolism; necessary for the normal functioning of the peripheral and central nervous system. Treatment with anti-tuberculosis drugs can lead to a deficiency of vitamin B 6 in the body, therefore, its daily requirement in patients with tuberculosis increases to 60 mg. The simultaneous administration of pyridoxine with ethambutol, rifampicin, isoniazid and pyrazinamide does not lead to microbiological or pharmacokinetic interactions of the listed substances.
Pharmacokinetics
- ethambutol: its maximum plasma concentration after oral administration is reached after about 2 hours and ranges from 6.4 to 7.6 mg / l. Such a rather high concentration of a substance in the plasma is due to a slowdown in its excretion under the influence of isoniazid. About 25% of the substance binds to plasma proteins. It is excreted in the urine: almost 70% is excreted unchanged, and the remaining 30% - in the form of carboxyl and aldehyde inactive metabolites;
- rifampicin: after oral administration of Isocomb to healthy volunteers, the maximum plasma concentration of rifampicin was 16.3 mg / l. Food intake reduces the absorption of the substance by about 30%. The maximum value of its concentration in plasma is reached after 1.5-2 hours, and the half-life is approximately 6 hours. Rifampicin, which is part of Isocomb, binds to plasma proteins 3 times less than other forms of rifampicin. Metabolism occurs in the liver; the main metabolite formed is deacetylrifampicin. This and other metabolites of the drug also exhibit antimicrobial properties against Mycobacterium tuberculosis. Approximately 30% of rifampicin is excreted in the urine;
- isoniazid: the rate of its absorption does not change due to the reception together with other substances that make up Isocomb. Isoniazid penetrates many fluids and tissues, including cerebrospinal fluid. The maximum concentration in blood plasma is reached after 2 hours and is 6.6 mg / l. The half-life is 5.8 hours. Under the influence of pyrazinamide, the excretion of isoniazid is slowed down. This explains its high plasma concentration and long half-life. Isoniazid hardly binds to plasma proteins. The main metabolites are isonicotinic acid and N-acetylisoniazid. About 80–90% of isoniazid is excreted in the urine and 10% is excreted in the feces. The excretion of the substance is carried out within 24 hours;
- pyrazinamide: the maximum plasma concentration is reached after 3 hours and is 24.1 mg / l. The average half-life is 17 hours. The main active metabolite is pyrazinic acid. It is excreted in the urine, mainly in the form of metabolites (up to 70%) and in unchanged form (about 4%);
- pyridoxine hydrochloride: rapidly absorbed throughout the small intestine, but the most active absorption of the substance occurs in the jejunum. Undergoes hepatic metabolism with the formation of active metabolites - pyridoxamine phosphate and pyridoxal phosphate. Pyridoxal phosphate is about 90% bound to plasma proteins. Active metabolites penetrate well into all tissues and organs. The main part is accumulated in the liver, a smaller amount in the central nervous system and muscles. Pyridoxine crosses the placental barrier and passes into breast milk. The half-life is long and ranges from 15 to 20 days. Excretion is carried out by the kidneys.
Indications for use
Isocomb is used for the treatment of newly diagnosed various forms and localizations of tuberculosis, in which there are or are absent bacterial secretions (mycobacterium tuberculosis, sensitive to the main anti-tuberculosis drugs).
Contraindications
- exacerbation of gastrointestinal diseases;
- liver disease in the acute phase;
- thrombophlebitis;
- eye diseases (inflammatory diseases of the organ of vision, cataracts, inflammation of the optic nerve, diabetic retinopathy);
- gout;
- diseases of the central nervous system (including epilepsy and other diseases characterized by a tendency to seizures);
- children and adolescents under the age of 13;
- period of pregnancy;
- lactation period;
- increased individual sensitivity to any of the main or auxiliary components of Isocomb tablets.
Isocomb, instructions for use: method and dosage
Isocomb tablets are taken orally, 30-40 minutes before breakfast (on an empty stomach).
Dosing of the drug is carried out according to rifampicin, based on the calculation of 10 mg of the substance per kg of body weight (no more than 5 tablets in total).
Depending on the nature of the tuberculosis infection, the course of treatment is from 2 to 4 months. Patients weighing more than 80 kg in the evening are additionally prescribed isoniazid (at the rate of 10 mg / kg per day). According to indications, it is possible to combine Isocomb with intramuscular injection of streptomycin at a dose of 15 mg / kg body weight once a day.
Side effects
Side effects of Isocomb are due to individual substances that are part of it.
Undesirable side effects associated with the presence of ethambutol in the drug:
- digestive system: nausea, loss of appetite, gastralgia, vomiting, increased activity of liver enzymes;
- nervous system and sensory organs: headache, feeling of weakness, disorientation, dizziness, depression, impaired consciousness, hallucinations, optic neuritis (impaired color perception, mainly red and green, decreased visual acuity, scotoma, color blindness), peripheral neuritis (itching, paresis, numbness, paresthesia in the limbs);
- immune system: itching, skin rash, fever, dermatitis, arthralgia, anaphylactic reactions;
- others: exacerbation of existing gout, increased levels of uric acid in the blood.
Possible side reactions due to rifampicin:
- digestive system: loss of appetite, nausea, erosive gastritis, vomiting, pseudomembranous enterocolitis, diarrhea, hepatitis, increased activity of liver enzymes, an increase in the amount of bilirubin in the blood serum;
- nervous system: decreased visual acuity, disorientation, headache, impaired coordination of movements of various muscles;
- urinary system: interstitial nephritis, renal necrosis;
- allergic reactions: bronchospasm, urticaria, fever, eosinophilia, arthralgia, Quincke's edema;
- others: exacerbation of existing gout, increased level of uric acid in the blood, induction of porphyria, leukopenia, menstrual pain, myasthenia gravis; when resuming therapy after a break or as a result of irregular pill intake - skin reactions, flu-like symptoms (headache, fever, muscle pain, dizziness, chills), acute renal failure, thrombocytopenic purpura, hemolytic anemia.
Side effects of Isocomb that can be caused by isoniazid:
- digestive system: gastralgia, vomiting, nausea, toxic hepatitis;
- nervous system and sensory organs: dizziness, unusual weakness or fatigue, insomnia, headache, numbness of the limbs, irritability, paresthesia, psychosis, euphoria, depression, mood changes, optic neuritis, peripheral neuropathy, multiple nerve damage, increased seizure frequency (in patients epilepsy);
- cardiovascular system: angina pectoris, palpitations, increased blood pressure;
- allergic reactions: itchy skin, skin rash, arthralgia, fever;
- others: tendency to hemorrhage and bleeding, heavy menstruation, breast enlargement in men.
Undesirable side reactions of Isocomb due to pyrazinamide:
- digestive system: a feeling of a metallic taste in the mouth, nausea, exacerbation of peptic ulcers, vomiting, jaundice, decreased appetite, yellow atrophy of the liver, pathological enlargement of the liver, liver soreness;
- nervous system: headache, irritability, dizziness, depression, sleep disturbances, convulsions, hallucinations, confusion;
- musculoskeletal system: myalgia, arthralgia;
- urinary system: interstitial nephritis, difficulty urinating;
- hematopoietic system: porphyria, thrombocytopenia, enlargement of the spleen, sideroblastic anemia, increased blood clotting, vacuolization of erythrocytes;
- immune system: hives, skin rash;
- others: exacerbation of existing gout, increase in body temperature, an increase in the content of uric acid in the blood, photosensitivity, acne, an increase in the concentration of iron in the serum.
The list of side effects of pyridoxine hydrochloride is quite small: the patient may experience hypersecretion of hydrochloric acid, a feeling of tightness and numbness in the extremities may appear, sometimes allergic reactions occur, in rare cases - itching and a rash on the skin.
Treatment with a multicomponent drug reduces the drug load on the patient by 3 times, therefore the tolerance of Isocomb is better than the tolerance of each of its components separately.
Overdose
Data on Izokomb's overdose were not provided.
special instructions
Influence on the ability to drive vehicles and complex mechanisms
There is no information on the effect of Isocomb on the patient's psychomotor functions. However, given some of the side effects of the drug (dizziness, disorientation, decreased visual acuity), work that requires a high concentration of attention and a quick reaction should be performed with caution until the individual reaction to the drug is clarified.
Application during pregnancy and lactation
Isocomb is contraindicated in pregnant and lactating women.
Pediatric use
Isocomb is not used to treat children and adolescents under the age of 13.
For violations of liver function
In patients with liver disease in the acute phase, the use of the drug is contraindicated.
Drug interactions
The combined use of ethambutol, rifampicin, isoniazid and, especially, pyrazinamide significantly increases their antimicrobial properties against mycobacterium tuberculosis.
By inducing some enzymes of the cytochrome P450 system, rifampicin accelerates the metabolism of phenytoin, quinidine, cimetidine, prednisolone, cyclosporine, antifungal agents, hormonal contraceptives and oral anticoagulants. The simultaneous administration of rifampicin with ofloxacin and lomefloxacin reduces the antimicrobial effect of these combinations against mycobacterium tuberculosis. The bioavailability of rifampicin decreases in the case of combined use with opioid analgesics and antacids. PASK (para-aminosalicylic acid) reduces the absorption of rifampicin, pyrazinamide slows down its excretion (the risk of hepatotoxicity increases), and isoniazid reduces its association with plasma proteins. Pyrazinamide also inhibits the excretion of isoniazid, increasing its serum concentration.
Monoamine oxidase inhibitors increase the risk of cardiovascular and central nervous system adverse reactions to isoniazid, while glutamic acid and pyridoxine reduce this risk. Cycloserine increases the neurotoxicity of isoniazid.
Aluminum hydroxide slows down the absorption of ethambutol. The neurotoxic effect of ethambutol is enhanced by simultaneous use with carbamazepine, ciprofloxacin, quinine, imipenem, aminoglycosides and lithium salts. Ethambutol enhances the antimicrobial properties of other anti-tuberculosis drugs.
Pyridoxine hydrochloride reduces the effectiveness of levodopa, and also reduces the likelihood of neurotoxic effects of anti-TB drugs.
Analogs
Repin B6, Laslonvita, Protub-4 plus, Iso-Eremfat, Izopask, Kombitub, Izozid comp.
Terms and conditions of storage
Store in a dark, dry place, out of reach of children, at a temperature not exceeding 25 ° C.
The shelf life of the tablets is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Isocombe
As with other anti-tuberculosis drugs, there are very few reviews about Isocombe. Patients note the effectiveness of the drug, but at the same time speak of a high probability of occurrence of undesirable side reactions from various systems and organs (neurotoxicity, hepatotoxicity, psychosis, depression, etc.).
Price for Isocomb in pharmacies
The tablets can only be purchased by prior order. Price for Isocomb in packs of 50 pcs. is about 1260 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
