Protech

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROTECH (PROTECH)

Composition:

Active substance: protionamide;

1 tablet contains 250 mg of protionamide;

Excipients: sodium croscarmellose, crospovidone, copovidone, silicon dioxide anhydrous colloidal, hypromellose (hydroxypropylmethylcellulose), lactose monohydrate, microcrystalline cellulose, magnesium stearate, titanium dioxide (E 171), polyethylene glycol 6000 (macrogol 6000), yellow azo dye FCF (E 110).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: round, film-coated tablets of orange color, with convex upper and lower surfaces. When broken and examined under a magnifying glass, a yellow core surrounded by a single continuous layer is visible.

Pharmacotherapeutic group. Agents acting on mycobacteria. Antituberculosis agents. Thiocarbamide derivatives. Protionamide.

ATC code J04A D01.

Pharmacological properties.

Pharmacodynamics.

Prothionamide is a reserve antituberculosis agent belonging to the group of thiocarbamide derivatives, chemically closely related to isoniazid. The drug exerts a bacteriostatic effect and, at higher concentrations, a bactericidal effect against certain species of mycobacteria causing tuberculosis. The antituberculosis activity is due to inhibition of mycolic acid synthesis in mycobacteria. The minimum inhibitory concentration (MIC) against Mycobacterium tuberculosis is 0.6 mg/L. Prothionamide is always used in combination with other antituberculosis drugs for the treatment of tuberculosis, which usually lasts 6–12 months, in order to prevent the development of resistant mycobacteria.

Pharmacokinetics.

Well absorbed after oral administration. Maximum plasma concentration (1–1.4 mg/L) is reached within 2 hours after oral intake. It distributes into all body tissues and fluids, including cerebrospinal fluid. It is mainly excreted in the urine; only 0.1% of the drug is excreted in feces.

Clinical characteristics.

Indications.

Treatment, as part of combination therapy with other antituberculosis agents, of all forms of tuberculosis when first-line drug therapy is ineffective.

Also used as an alternative to clofazimine in the treatment of leprosy.

Contraindications.

Hypersensitivity to prothionamide or to any other components of the drug. Acute and chronic liver diseases (including acute hepatitis, liver cirrhosis), acute gastritis, gastric and duodenal ulcer in the stage of exacerbation, erosive-ulcerative colitis, chronic alcoholism, diabetes mellitus, porphyria, seizures, psychoses.

Interaction with other medicinal products and other types of interactions.

Concomitant use of prothionamide and isoniazid increases the blood concentration of prothionamide. Therefore, the dose of prothionamide should be reduced.

The hepatotoxicity of the drug increases when used in combination with rifampicin, thiacetazone, isoniazid, and pyrazinamide. Prothionamide may increase serum concentrations of isoniazid and barbiturates by inhibiting the metabolism of isoniazid.

The possible additive hepatotoxic effect should also be considered when prothionamide is used in combination with hormonal contraceptives.

Particular attention should be paid to the possibility of psychiatric disturbances when used concomitantly with isoniazid, cycloserine, and terizidone.

Concomitant alcohol consumption leads to enhanced excitatory effects on the central nervous system.

Dosage reduction of insulin or oral hypoglycemic agents is required when used concomitantly with prothionamide.

Concomitant use of the drug with thiocarbamides should be avoided (cross-resistance).

Special precautions.

The drug should be used only after confirmation of microbial sensitivity to it. It is best to take the medication during breakfast with a small amount of water or orange juice. If gastrointestinal side effects occur, the daily dose may be divided into two administrations. The dose of the drug should be increased gradually!

Since the drug is consistently used in combination with other antituberculosis agents, regular monitoring of serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase is required. Monitoring should be initiated prior to starting therapy and continued at regular intervals. Patients must monitor visual function and thyroid gland function during treatment with protionamide.

Use with caution in patients with depression or other psychiatric disorders, acute renal failure, or hemoptysis.

Alcohol consumption is contraindicated during treatment due to the risk of central nervous system stimulation. When used concomitantly with isoniazid and cycloserine, particular attention should be paid to the possible development of psychiatric disturbances.

Special attention should also be paid to the appearance of blood streaks in sputum and to the occurrence of acute gastritis, acute gastric or duodenal ulcer.

Very rare cases of effects on prothrombin and fibrinogen have been observed. Particular caution is required in patients with coagulopathy.

Blood glucose levels should be monitored in patients with diabetes mellitus. Treatment with protionamide may complicate blood glucose control.

Attention should be paid to skin and mucous membrane changes, which may be the first signs of pellagra-like adverse reactions caused by deficiency of nicotinic acid and vitamin B. If these symptoms appear, the drug should be discontinued.

The drug contains lactose. Patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

The presence of the azo dye sunset yellow FCF (E 110) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Do not use during pregnancy.

Breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

Caution should be exercised when driving vehicles or operating potentially hazardous machinery, or such activities should be avoided due to the possibility of psychiatric, nervous system, and visual adverse reactions (see section "Adverse reactions").

Method of Administration and Dosage.

For use in adults and children aged 14 years and older. Treatment should be initiated at a dose of 250 mg (1 tablet) 1–2 times daily, unless otherwise prescribed by a physician. The dose may be increased to 3–4 tablets daily depending on the therapeutic response. The maximum daily dose is 1 g for adults and should not exceed 750 mg (3 tablets daily) for children aged 14 years and older. The drug should be used in children only on a physician's prescription and under medical supervision.

When used in combination with isoniazid, the dose of the drug may be reduced by half.

The daily dose for elderly patients (over 60 years of age) or for patients with body weight less than 50 kg should not exceed 750 mg; typically, 250 mg twice daily is prescribed.

Duration of treatment: 8–9 months.

Children.

For use in children aged 14 years and older only on a physician's prescription and under medical supervision.

Overdose.

Symptoms: nausea, vomiting, dryness and metallic taste in the mouth, liver function disturbances with signs of hepatitis and jaundice, dizziness, headache, difficulty concentrating, psychiatric disturbances, hypoglycemia in diabetic patients, or exacerbation of other adverse reactions.

Treatment: symptomatic therapy, gastric lavage. There is no specific antidote.

Adverse Reactions

Adverse effects associated with protionamide therapy involve the gastrointestinal tract, liver, skin, endocrine and nervous systems. These side effects usually resolve quickly after discontinuation of the drug. Gradual dose escalation may reduce the likelihood of adverse reactions. Dose reduction and/or combination with antiemetic agents can also be effective.

Adverse reactions reported during protionamide use are listed below by system organ classes and frequency of occurrence: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (≤ 1/10,000), frequency not known (cannot be estimated based on available data).

Blood and lymphatic system disorders: Known cases of anemia, methemoglobinemia, hypoprothrombinemia and hypofibrinogenemia, thrombocytopenia, purpura; possible bone marrow dysfunction.

Immune system disorders: Isolated cases of allergic reactions: skin rashes.

Endocrine system disorders: Rare: gynecomastia (enlargement of breast glands in males), dysmenorrhea, amenorrhea and hypothyroidism (thyroid gland dysfunction), impotence.

Metabolism and nutrition disorders: Rare: fluctuations in blood glucose levels, development of hypoglycemia in patients with diabetes mellitus.

Psychiatric disorders: Uncommon: difficulty concentrating, mental disturbances, psychosis, confusion, agitation, depression, anxiety, asthenia; isolated cases: suicidal ideation.

Nervous system disorders: Common: dizziness, headache; rare: seizures, paroxysmal convulsions; possible development of polyneuropathy with paresthesia, muscle weakness and ataxia, especially when the drug is used in combination with isoniazid; sleep disturbances (insomnia or somnolence); in isolated cases – peripheral neuropathy, polyneuropathy, algodystrophy. Concomitant use of other antituberculosis drugs such as isoniazid or cycloserine may lead to increased adverse effects on the central nervous system. The same effect may be caused by concomitant alcohol consumption.

Eye disorders: Cases reported: optic neuritis, optic nerve paralysis, blurred vision, visual disturbances including diplopia.

Ear and labyrinth disorders: Isolated cases: tinnitus, hearing impairment.

Respiratory, thoracic and mediastinal disorders: Isolated cases: hemoptysis.

Gastrointestinal disorders: Very common: metallic or sulfurous taste in the mouth, dry mouth, yet increased salivation, loss of appetite, anorexia, nausea; uncommon: vomiting, heartburn, abdominal pain, bloating, diarrhea or constipation, flatulence.

Hepatobiliary disorders: Common: increased transaminase levels, which decrease upon discontinuation; rare: sometimes marked liver function abnormalities with signs of hepatitis and jaundice. The hepatotoxicity of the drug depends on the degree of pre-existing liver dysfunction, e.g., liver damage due to alcoholism or following surgery. These adverse effects are particularly observed during combination therapy with isoniazid, rifampicin and pyrazinamide. Cases of severe hepatitis with jaundice and one case of liver failure have been reported.

Skin and subcutaneous tissue disorders: Cases reported: pellagra-like reactions, photo dermatitis, angular cheilitis, stomatitis, acneiform eruptions, cheilitis, glossitis and alopecia.

Musculoskeletal and connective tissue disorders: Cases reported: arthralgia, arthritis, muscle weakness.

Renal and urinary disorders: Cases reported: urolithiasis.

Cardiac disorders: In individual cases – postural hypotension, tachycardia.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Physicians should report any suspected adverse reactions in accordance with applicable regulatory requirements.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging.

10 tablets in a blister. 5 or 10 blisters in a cardboard box.

10 tablets in a blister. 50 or 100 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "Tekhnolohiya".

Manufacturer's address and place of business.

8 Stara Prorizna Street, Uman, Cherkasy region, 20300, Ukraine.