Iso-Eremfat (Tablets) Instructions for Use

Marketing Authorization Holder

Riemser Arzneimittel, AG (Germany)

Manufactured By

Fatol Arzneimittel subsidiary of Riemser Arzneimittel, AG (Germany)

Promotion

SVICH, LLC (Russia)

ATC Code

J04AM02 (Rifampicin and Isoniazid)

Active Substances

Rifampicin (Rec.INN registered by WHO)

Isoniazid (Rec.INN registered by WHO)

Dosage Forms

	Iso-Eremfat	Film-coated tablets, 100 mg+150 mg: 100 pcs.
		Film-coated tablets, 150 mg+300 mg: 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets red-brown in color, round, biconvex.

Excipients: microcrystalline cellulose – 11.785 mg, copovidone – 4 mg, croscarmellose sodium – 19.58 mg, crospovidone – 1.055 mg, hypromellose – 2.2 mg, magnesium stearate (vegetable) – 3.89 mg, colloidal silicon dioxide – 2.9 mg, sorbitol – 99.7 mg, talc – 3.89 mg.

Shell composition: hypromellose – 7.25 mg, macrogol 6000 – 0.76 mg, propylene glycol – 0.83 mg, iron oxide red (E172) – 0.42 mg, iron oxide yellow (E172) – 0.42 mg, titanium dioxide (E171) – 0.32 mg.

100 pcs. – polypropylene containers (1) – cardboard packs.

Film-coated tablets red-brown in color, round, biconvex, with a score on one side.

Excipients: microcrystalline cellulose – 20.17 mg, copovidone – 6 mg, croscarmellose sodium – 38 mg, crospovidone – 2.1 mg, hypromellose – 3.333 mg, magnesium stearate (vegetable) – 7.6 mg, colloidal silicon dioxide – 5.8 mg, sorbitol – 199.4 mg, talc – 7.6 mg.

Shell composition: hypromellose – 10.88 mg, macrogol 6000 – 1.14 mg, propylene glycol – 1.24 mg, iron oxide red (E172) – 0.63 mg, iron oxide yellow (E172) – 0.63 mg, titanium dioxide (E171) – 0.48 mg.

100 pcs. – polypropylene containers (1) – cardboard packs.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Combined antitubercular agent

Pharmacological Action

[I] – Instructions for medical use approved by the Pharmacological Committee of the Ministry of Health of the Russian Federation on 27.06.2000

Iso-Eremfat contains a combination of two antituberculosis drugs – rifampicin and isoniazid.

Rifampicin and Isoniazid have the greatest activity against rapidly growing extracellularly located microorganisms, but also have a bactericidal effect on intracellularly located pathogens.

Rifampicin.

Rifampicin is also active against slowly and intermittently growing forms of Mycobacterium tuberculosis. The mechanism of action of rifampicin involves inhibition of DNA-dependent RNA polymerase. In tuberculosis, Rifampicin has a bactericidal effect on both intracellular and extracellular microorganisms.

Isoniazid

Isoniazid has a bactericidal effect on actively dividing cells of Mycobacterium tuberculosis. Its mechanism of action involves inhibition of the synthesis of mycolic acids, which are a component of the mycobacterial cell wall. For Mycobacterium tuberculosis, the minimum inhibitory concentration of isoniazid is 0.05-0.025 mg/L. Resistance to isoniazid develops rapidly.

Pharmacokinetics

After oral administration of Iso-Eremfat, its active components are rapidly and sufficiently completely absorbed from the gastrointestinal tract. C_max of active components in plasma is reached by the second hour and remains at a detectable level for up to 8 hours.

Rifampicin

When taken with food, the absorption of rifampicin, which is part of Iso-Eremfat, is reduced by 30%.

C_max of rifampicin in plasma is reached after 2 hours. Rifampicin is widely distributed in the body. Approximately 80% of the administered dose binds to plasma proteins. Rifampicin is metabolized in the liver to desacetylrifampicin; this metabolite is active. Rifampicin is excreted from the body in the urine (up to 30% of the administered dose).

Isoniazid

After administration of Iso-Eremfat to healthy adults, C_max of isoniazid in plasma is reached after 2 hours. T_1/2 of isoniazid from plasma is 2-6 hours. Isoniazid undergoes significant presystemic metabolism in the wall of the small intestine and liver, resulting in its plasma concentration in patients with a rapid acetylation process being half that in patients with a slow acetylation process.

Up to 95% of the administered dose of isoniazid is excreted in the urine within the first 24 hours. Less than 10% of the administered dose is excreted in the feces.

The main excretion products in urine are N-acetylisoniazid and isonicotinic acid.

Indications

• Treatment of the initial stage of pulmonary tuberculosis;
• Treatment of the initial stages of extrapulmonary tuberculosis.

ICD codes

Dosage Regimen

The drug is prescribed to adults. The daily dose is established taking into account the patient’s body weight. The following drug administration regimens in the continuation phase are possible. (The initial phase involves the prescription of Iso-Eremfat + streptomycin/ethambutol for 2 months).

Short course of treatment

Continuation phase (4 months or more): Isoniazid and Rifampicin (Iso-Eremfat) are prescribed every day or 2-3 times a week.

Treatment of tuberculosis should continue for 6 months and for at least another 3 months after the cessation of bacterial excretion.

Long course of treatment

Patients with resistance or extrapulmonary forms of tuberculosis may require a longer course of therapy (continuation phase).

In case of HIV infection, treatment should be continued for 9 months and for at least another 6 months after the cessation of bacterial excretion. The tablet containing 150 mg of rifampicin and 100 mg of isoniazid is taken orally 1-2 hours before meals, 4 tablets/day once, by patients whose body weight does not exceed 50 kg, for 2 months.

The tablet containing 300 mg of rifampicin and 150 mg of isoniazid is taken orally 1-2 hours before meals, 2 tablets/day once, by patients whose body weight is at least 60 kg, for 2 months.

It is possible to use the drug in combination with other antituberculosis drugs, such as streptomycin.

Simultaneous administration of pyridoxine is recommended for elderly patients, individuals predisposed to neuropathy (patients with diabetes mellitus).

Adverse Reactions

Side effects during treatment with Iso-Eremfat are determined by its active ingredients.

Rifampicin

Rifampicin can cause side effects from the gastrointestinal tract, such as heartburn, discomfort in the epigastrium, anorexia, vomiting, intestinal colic, and diarrhea. Some patients experience headache, drowsiness, weakness, ataxia, dizziness, confusion, visual disturbances, muscle weakness, fever, limb pain, itching, urticaria, skin rashes, and eosinophilia, sore throat, and tongue tenderness. In men, toxic liver damage is occasionally observed, which usually develops in the first two weeks after starting treatment.

Isoniazid

Long-term use of isoniazid causes peripheral neuropathy in 3.5-17% of patients. There is a sensation of tingling and numbness in the fingers and toes, some patients develop muscle weakness, headache, dizziness, nausea, vomiting, drug-induced hepatitis, gynecomastia in men and menorrhagia in women. Prophylactic and therapeutic use of isoniazid as monotherapy or in combination with antituberculosis drugs is associated with a significant risk of toxic liver damage.

Contraindications

• Hypersensitivity to any ingredient of the drug;
• Epilepsy and tendency to convulsive seizures, in case of a history of poliomyelitis;
• Impaired liver and kidney function;
• Gout;
• Thrombophlebitis;
• Severe atherosclerosis;
• Children under 12 years of age;
• Body weight less than 45 kg;
• First trimester of pregnancy;
• Breastfeeding period.

Use in Pregnancy and Lactation

Iso-Eremfat should not be used in the first trimester of pregnancy and during breastfeeding. The possibility of using Iso-Eremfat during later pregnancy can only be decided by a doctor after assessing the risk/benefit ratio. When used in the last weeks of pregnancy, Iso-Eremfat can cause postpartum bleeding in the mother or newborn, for which vitamin K is used for treatment.

Use in Hepatic Impairment

Contraindicated: impaired liver function.

Iso-Eremfat should be prescribed with caution to patients with liver diseases.

Use in Renal Impairment

Contraindicated: impaired kidney function.

Pediatric Use

Contraindicated: children under 12 years of age.

Geriatric Use

Iso-Eremfat should be prescribed with caution to elderly patients.

Special Precautions

During treatment with Iso-Eremfat, monitoring of kidney, liver, and blood function is necessary.

When prescribing Iso-Eremfat, it should be taken into account that urine, feces, saliva, and tears may turn orange.

Iso-Eremfat should be prescribed with caution to patients with liver diseases, elderly and debilitated patients, as well as patients suffering from chronic alcoholism.

Drug Interactions

Rifampicin

Rifampicin is known to induce some cytochrome P450 system enzymes. It has been established that Rifampicin accelerates the metabolism of phenytoin, quinidine, oral anticoagulants, and antifungal drugs.

Isoniazid

Isoniazid enhances the effects of phenytoin, such as drowsiness and ataxia.

Prednisolone can significantly reduce the plasma concentration of isoniazid in both slow and fast acetylators, but this effect is more pronounced in slow acetylators.

Storage Conditions

List B.

Store at a temperature not exceeding 25°C (77°F). Protect from moisture and light. Keep out of reach of children.

Shelf Life

The shelf life is 3 years. Do not use the drug after the expiration date.

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.