Ripeg - instructions for use, doses, side effects, contraindications

Core: Active substances: isoniazid (in terms of 100% substance) - 75 mg, pyrazinamide (in terms of 100% substance) - 400 mg, rifampicin (in terms of 100% substance) -150 mg, ethambutol hydrochloride (in terms of 100 % substance) - 275 mg. Auxiliary substances: sorbitol (sorbitol) - 13,950 mg, povidone (polyvinylpyrrolidone) - 5,030 mg, potato starch - 20,160 mg, carmellose sodium (sodium carboxymethylcellulose) - 1,320 mg, sodium lauryl sulfate - 6,300 mg, croscarmellose sodium (impellose) - 25,200 mg, magnesium stearate - 6,300 mg, microcrystalline cellulose - to obtain a core with a mass of 1260 mg.

Shell(talc) 2,270 mg, propylene glycol 8,038 mg, iron (III) oxide red 2,778 mg, quinoline yellow (E-104) 0.294 mg, titanium dioxide 2.242 mg, hypromellose hydroxypropylmethylcellulose, to prepare a film coated tablet , with a mass of 1300 mg.

Description:The tablets are biconvex, oblong with a risk, covered with a film coating of brown color.At the break, the core is red-brown with dark and light impregnations.

Pharmacotherapeutic group:Anti-tuberculosis drug combined

ATX: & nbsp

J.04.A.M.06 Isoniazid in combination with pyrazinamide, rifampicin and ethambutol

Pharmacodynamics:

Combined drug, has antibacterial, anti-tuberculosis action, is active against Mycobacterium tuberculosis at different stages of development. The combined use of the active substances in the preparation reduces the risk of resistance that develops with monotherapy.

Isoniazid

It acts bacteriostatically. Is a prodrug - mycobacterial catalase-peroxidase metabolizes isoniazid to the active metabolite, which, when bound to the enoyl (acyl transfer protein) reductase of fatty acid siutase II, disrupts the conversion of delta-2-unsaturated fatty acids into mycolic acid. The latter is a branched chain fatty acid that, when combined with arabinogalactan (polysaccharide), participates in the formation of the components of the cell wall of Mycobacterium tuberculosis. Isoniazid is also an inhibitor of mycobacterial catalase peroxidase, which reduces the protection of the microorganism against reactive oxygen species and hydrogen peroxide. Isoniazid It is also active against a small amount of Mycobacterium kansasii strains (infections caused by the data agent, before treatment is necessary to determine susceptibility to isoniazid). Minimal inhibitory concentration for M. tuberculosis (MIC) was 0.025-0.05 mg / L. Isoniazid has a moderate effect on slowly and rapidly growing atypical mycobacteria. The antimicrobial activity of isoniazid in combination with rifampicin is increased by 1.5 times.

Pyrazinamide

Pyrazinamide has a bactericidal action at acidic pH values. To manifest the bactericidal activity of pyrazinamide, the preparation is subjected to enzymatic conversion into the active form - pyrazinic acid. At acid pH values, the pyrazinamide MIC is 20 mg / L in vitro.

Rifampicin

The mechanism of action of rifampicin is to block the DNA-dependent RNA polymerase. With tuberculosis infection rifampicin has a bactericidal effect on intracellular and extracellularly located microorganisms. For mycobacteria tuberculosis MIC for rifampicin is 2 mg / l. The anti-tuberculosis activity of pyrazinamide in combination with rifampicin and isoniazid increases more than 2-fold.

Etambugol

Ethambutol acts bacteriostatically; penetrates into actively growing mycobacterial cells, inhibiting the synthesis of RNA, disrupts cellular metabolism, causes the cessation of reproduction and death of bacteria. It is active only for intensively dividing cells. Suppresses the growth and reproduction of mycobacterium tuberculosis, resistant to streptomycin, isoniazid, sodium para-aminosalicylate, ethionamide, kanamycin. The MIC of ethambutol is 0.78-2.0 mg / l. The antimicrobial activity of ethambutol in combination with isoniazid increased by 2 times.

Pharmacokinetics:

Isoniazid

After taking the drug in healthy adults, the maximum concentration of isoniazid in plasma reaches 4.75 μg / ml after 2 hours. The half-life of isoniazid from plasma is 2-6 hours. Isoniazid is subjected to a pronounced pre-systemic metabolism in the wall of the small intestine and liver, as a result of which its plasma concentration in patients with a fast acetylation process is half the concentration in patients with a slow acetylation process. The apparent volume of isoniazid distribution is 61% of body weight. Isoniazid is present in effective concentrations in many tissues and biological fluids, including cerebrospinal fluid. Up to 95% of the accepted dose of isoniazid is excreted by the kidneys within 24 hours, the rest is excreted through the intestine. The main products of urinary excretion are N-acetylisosodium and isonicotinic acid.

Pyrazinamide

After taking the drug in healthy adults, the maximum concentration of pyrazinamide in plasma reaches 24.13 μg / ml after 3 hours. The half-life of pyrazinamide is 10-24 hours. The drug is widely distributed in the body, it penetrates well into tissues and biological fluids, including cerebrospinal fluid. Its concentrations in the cerebrospinal fluid are almost identical to those in the blood. In the liver pyrazinamide turns into the main active metabolite - pyrazinic acid. Approximately 30-40% of the accepted dose is excreted by the kidneys in the form of pyrazinic acid and 3.4% in the form of unchanged pyrazinamide.

Rifampicin

After taking the drug in healthy adults, the maximum concentration of rifampicin in plasma reaches 7.84 μg / ml. If taken together with food, the absorption of rifampicin is reduced by 30%.The maximum concentration of rifampicin in plasma is reached after 2 hours. Rifampicin widely distributed in the body, quickly penetrating into organs and tissues (the highest concentration is created in the liver and kidneys), also penetrates into bone tissue. Concentration in the saliva is 20% of the plasma. Rifampicin penetrates the blood-brain barrier only in case of inflammation of the meninges. Penetrates through the placenta (concentration in fetal plasma - 33% of the concentration in the plasma of the mother) and in breast milk (breast-fed children receive no more than 1% of the therapeutic dose of the drug). Approximately 80% of the dose is associated with plasma proteins. The half-life of rifampicin is, on average, 3.35 + 0.66 h.

Rifampicin is metabolized in the liver to pharmacologically active deacetyltrifampicin, excreted from the body by the kidneys (up to 30% of the dose taken).

Ethambutol

After taking the drug in healthy adults, the maximum concentration of ethambutol in plasma reaches 3.45 μg / ml after 2 hours. Further, the concentration decreases in a two-phase manner: at the beginning, the elimination half-life is 4 hours and then 10 hours. Ethambutol well penetrates into tissues and organs (into the cerebrospinal fluid only with meningitis). About 50-70% of the accepted dose is excreted by the kidneys unchanged, and the rest - in the form of aldehyde and carboxyl metabolites. The average volume of distribution is 3.89 l / kg. About 10-40% of the drug binds to plasma proteins. A small portion of the dose taken is metabolized in the liver and, possibly, in other tissues. Metabolite is excreted by the kidneys. In patients with impaired renal function, ethambutol elimination is slowed down.

Indications:The combined preparation RIPEG® is used for chemotherapy of newly diagnosed patients with respiratory tuberculosis and extrapulmonary forms of tuberculosis, with the presence or absence of bacterial excretion, without drug resistance to the drugs that make up the drug.

Contraindications:

- hypersensitivity to any ingredient in the drug;

- visual impairment (diabetic retinopathy, optic nerve damage, inflammatory eye diseases);

- Epilepsy and a tendency to convulsive seizures in the case of a previous history of poliomyelitis;

- diseases of the liver and gastrointestinal tract in acute stage;

- thrombophlebitis and severe atherosclerosis;

- the presence of drug or alcohol dependence;

- gout;

- jaundice, hepatitis;

- chronic renal failure and other renal dysfunction;

- liver failure;

severe pulmonary heart failure;

- lactation period;

- childhood;

- deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:in pregnancy, psychosis, hyperuricemia, the elderly

Pregnancy and lactation:

Use during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Therapy during pregnancy (especially in the first trimester) is possible only by "vital" indications.

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.

If it is necessary to use the drug during lactation, breastfeeding should be abolished.

Dosing and Administration:

To adults.The drug is taken orally for 1 to 2 hours before meals. Doses are calculated based on the recommended daily doses of 4 components: ethambutol - 15-25 mg / kg, rifampicin - 8-12 mg / kg (not more than 600 mg), isoniazid - 5-10 mg / kg (not more than 300 mg), pyrazinamide - 20-35 mg / kg (not more than 3 g). The course of treatment - 1-3 months. The maximum daily dose of ethambutol is not more than 2000 mg. It is possible to use the drug in combination with other anti-tuberculosis drugs, such as streptomycin and etc.

Side effects:

The side effects of RIPEG are determined by the active ingredients in the formulation.

Isoniazid

From the nervous system: fatigue, weakness, irritability, euphoria, insomnia, paresthesia, peripheral neuropathy, seizures, toxic neuropathy, memory impairment, optic neuritis, polyneuritis, psychosis, mood change, depression; possible: headache, dizziness; more frequent seizures in patients with epilepsy.

From the cardiovascular system: heart palpitations, angina, increased blood pressure.

From the digestive system: nausea, vomiting, gastralgia, increased activity of "liver" transaminases, hyperbilirubinemia, bilirubinuria, jaundice, toxic hepatitis.

From the hematopoiesis: agranulocytosis, hemolytic, sideroblastic or aplastic anemia; thrombocytopenia, eosinophilia.

From the side of metabolism: hypovitaminosis Vb, pellagra, hyperglycemia, metabolic acidosis.

Allergic reactions: skin rash, itching, hyperthermia, arthralgia, lymphadenopathy, vasculitis.

Other: gynecomastia in men, menorrhagia in women.

Pyrazinamide

From the central nervous system: dizziness, headache, sleep disturbances, increased excitability, depression, in some cases - hallucinations, convulsions, confusion.

From the digestive system: nausea, vomiting, diarrhea, a "metallic" taste in the mouth, exacerbation of the peptic ulcer. Can cause a violation of liver function (decreased appetite, liver tenderness, hepatomegaly, jaundice, yellow atrophy of the liver).

From the hematopoiesis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.

From the musculoskeletal system: arthralgia, myalgia.

From the urinary system: dysuria, interstitial nephritis.

Allergic reactions: skin rash, hives.

Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitivity, increased serum iron concentration.

Rifampicin

From the nervous system: headache, decreased visual acuity, ataxia, disorientation.

From the digestive system: nausea, vomiting, diarrhea, decreased appetite, erosive gastritis, pseudomembranous colitis, increased activity of "hepatic" transaminases in the blood serum, hyperbilirubinemia, hepatitis.

From the urinary system: nephronecrosis, interstitial nephritis.

Allergic reactions: urticaria, eosinophilia, angioedema, bronchospasm, arthralgia, fever.

Other: leukopenia, dysmenorrhea, induction of porphyria, myasthenia gravis, hyperuricemia, exacerbation of gout.

With irregular therapy or with the resumption of treatment after a break, it is possible: flu-like syndrome, skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure.

Ethambutol

The most serious side effects of ethambul are: retrobulbar neuritis, manifested by a decrease in visual acuity, narrowing of the visual field,central or peripheral scotoma and a violation of color perception, especially distinguish between green and red colors

From the nervous system: confusion, disorientation, hallucinations, weakness, headache, dizziness, impaired consciousness, depression, peripheral neuritis (paresthesia in the limbs, numbness, paresis, itching).

From the digestive system: decreased appetite, nausea, vomiting, gastralgia, increased activity of "liver" transaminases.

Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.

Other: hyperuricemia, exacerbation of gout.

Overdose:

Symptoms: pulmonary edema, confusion, convulsions, peripheral neuropathy, impaired liver function, nausea, vomiting, impaired vision and hearing, slurred speech, respiratory depression, stupor, coma.

Treatment: gastric lavage, the appointment of activated charcoal, symptomatic therapy, forced diuresis, artificial ventilation, intravenous short-acting barbiturates, pyridoxine, osmotic diuretics, sodium bicarbonate in the development of metabolic acidosis.

Interaction:

Isoniazid

Isoniazid enhances the effects of phenytoin, such as drowsiness and ataxia. Prednisolone can significantly reduce the concentration of isoniazid in blood plasma in "slow" and "fast" acetylators, but this effect is more pronounced in "slow" acetylators. Isoniazid increases the frequency and severity of liver function disorders in combination with rifampicin in patients with previous liver disease. Preparations of para-aminosalicylic acid containing bentonite (aluminum hydrosilicate) are prescribed four hours after taking isoniazid. Antacids reduce the absorption of isoniazid.

Isoniazid reduces the effectiveness of oral contraceptive drugs, oral hypoglycemic drugs, theophylline, tolazomide, vitamin Bi (enhances its excretion); reduces the excretion of triazolam; reduces the content of Zn2 + in the blood (increases its excretion).

Pyrazinamide

When used simultaneously with drugs that block tubular secretion, it is possible to reduce their excretion and enhance toxic reactions. Strengthens the antituberculous action of lomefloxacin. Pyrazinamide slightly reduces the concentration of isoniazid in the blood serum, especially in "slow" acetylators.

Rifampicin

Reduces the activity of indirect anticoagulants, oral hypoglycemic drugs, hormonal contraceptives, cardiac glycosides, antiarrhythmic drugs (disopyramide, pirmenol, quinidine, mexiletine, tokainid), glucocorticosteroids, dapsone, phenytoin, hexobarbital, nortriptyline, benzodiazepines, theophylline, chloramphenicol, ketoconazole, itraconazole, cyclosporine, azathioprine, beta adrenoblockers, slow calcium channel blockers, enalapril, cimetidinerifampicin causes induction of cytochrome P450 isoenzymes, accelerating their metabolism).

Antacids, narcotic analgesics, anticholinergic drugs and ketoconazole reduce (in the case of simultaneous ingestion) bioavailability of rifampicin.

Ethambutol

Aluminum hydroxide disrupts the absorption of ethambutol and, therefore, it is necessary to use alternative antacids.

When combined with neurotoxic agents, the neurotoxic effect of ethambutol may be enhanced.

Special instructions:

Before the beginning of treatment it is recommended to conduct a full ophthalmologic

patient examination, which includes the definition of visual acuity, color

vision, visual fields and ophthalmoscopy. If prior to treatment,

corrective glasses, they should be worn during the evaluation of visual acuity. AT

During 1-2 years of therapy, a refractive error may develop that should be

corrected to obtain accurate research results. Study of severity

vision through a stenopic hole eliminates the error of refraction.

Against the backdrop of treatment, skin, sputum, sweat, feces, tear fluid, urine acquire an orange-

Red color. Can persistently stain soft contact lenses.

Do not interrupt (accidentally or intentionally) taking the drug without consulting a doctor.

Women during the treatment period are recommended to use non-hormonal methods of contraception.

During the treatment should not be used microbiological methods to determine the concentration of folic acid and cyanocobalamin in the blood serum. Caution should be used when using in elderly patients, due to the increased risk of developing toxic effects.

To avoid the development of a hepatotoxic effect during treatment, ethanol should be avoided. Eating certain types of cheese (Swiss, Cheshire) or fish (tuna, sardines) during eating can lead to itching of the skin, palpitation, chills and headache.

Pyrazinamide worsens the course of gout and diabetes, requires monitoring of kidney function, uric acid. In the case of a persistent increase in uric acid and exacerbation of gouty arthritis, the treatment is canceled.

Effect on the ability to drive transp. cf. and fur:The drug can cause headache and reduced visual acuity, caution is required when managing transport and working with mechanisms.

Form release / dosage:

Tablets, film-coated, 75 mg + 400 mg + 150 mg + 275 mg.

Packaging:

For 10 tablets in a planar cell package. 1,2,5, 10 contour squares with instructions for use in packs

from cardboard.

10, 20, 50, 100 tablets in polymer cans with screw-on lids or polyethylene terephthalate cans with first-tamper control covers with instructions for use in packs of cardboard.

Packing for hospitals

50, 100, 150, 200, 300, 500 contour packs together with an equal number of instructions for use in cardboard boxes.

For 500, 1000 tablets in polymer cans with screw caps. By 4, 6, 10, 12 cans together with an equal number of instructions for use in cardboard boxes.

Storage conditions:In dry, the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002246

Date of registration:24.09.2013/15.07.2015

Date of cancellation:2018-09-24

The owner of the registration certificate:BRYNTSALOV-A, CJSC BRYNTSALOV-A, CJSC Russia

Manufacturer: & nbsp

BRYNTSALOV-A, CJSC Russia

Information update date: & nbsp13.05.2016

Illustrated instructions

Instructions

Ripeg (Ripeg)