Protionamide-Akri^® (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

ATC Code

J04AD01 (Protionamide)

Active Substance

Protionamide (Rec.INN WHO registered)

Dosage Form

Protionamide-Akri®

Film-coated tablets, 250 mg: 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from light orange to dark orange in color, round, biconvex; roughness is allowed.

Excipients: microcrystalline cellulose, potato starch, povidone, hypromellose, colloidal silicon dioxide, magnesium stearate, sodium carboxymethyl starch, talc, macrogol, hydroxypropyl methylcellulose, titanium dioxide, yellow-orange dye (Orange S).

10 pcs. – contour cell blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

Second-line antituberculosis agent, acts bacteriostatically, blocks the synthesis of mycolic acids, which are the most important structural component of the Mycobacterium tuberculosis cell wall.

It has the properties of a nicotinic acid antagonist. In high concentrations, it disrupts the synthesis of the microbial cell protein and acts bactericidally. Effective against Mycobacterium tuberculosis resistant to first-line drugs.

Use in combination with other antituberculosis drugs reduces the likelihood of developing tuberculosis resistance.

Pharmacokinetics

Protionamide is rapidly absorbed from the gastrointestinal tract, achieving a C_max in blood plasma 2-3 hours after oral administration.

It penetrates into healthy and pathologically altered tissues (tuberculous foci and cavities in the lungs, serous and purulent pleural effusion, cerebrospinal fluid in meningitis). In the body, it is partially converted into a sulfoxide, which has tuberculostatic activity.

It is partially excreted unchanged (up to 15-20% of the administered dose) in urine and feces.

Indications

• Treatment of all forms of tuberculosis, including cases with pathogen resistance to other antituberculosis drugs (first-line) or their intolerance.

ICD codes

Dosage Regimen

The drug is taken orally after meals.

Adults are prescribed 0.25 g 3 times/day; with good tolerance – 0.5 g 2 times/day.

For patients over 60 years of age and with a body weight less than 50 kg, the daily dose should not exceed 0.75 g (more often prescribed as 0.25 g 2 times/day).

Children are prescribed at a rate of 10-20 mg/kg of body weight per day.

Adverse Reactions

Protionamide’s side effects manifest from the gastrointestinal tract, liver, skin, endocrine and nervous systems.

From the gastrointestinal tract: loss of appetite, nausea, vomiting, dry mouth and metallic taste. After drug withdrawal, these phenomena, as a rule, quickly disappear.

Often during treatment, an increase in blood transaminase levels is noted. Rarely, pronounced liver function disorders with signs of hepatitis and jaundice are noted. The hepatotoxicity of the drug depends on existing liver function disorders, such as liver damage due to alcoholism or after surgical interventions. These side effects are noted especially during combination therapy with isoniazid, rifampicin and pyrazinamide.

Skin reactions are rarely noted; in isolated cases, pellagra-like reactions have been described, correspondingly with a combination of skin manifestations and CNS disorders.

Sometimes disorders from the endocrine system are noted. Along with the development of hypoglycemia (decrease in blood sugar less than 50 mg%) in patients with diabetes mellitus, the development of gynecomastia (enlargement of mammary glands in men) has been described. Rarely, menstrual cycle disorders and impotence are noted, as well as hypothyroidism (decreased thyroid function).

Protionamide can sometimes cause disorders of the peripheral and central nervous system. In combination with isoniazid, cases of polyneuropathy have been described. Taking protionamide can cause dizziness, headaches, impaired concentration, mental disorders (rarely – optic neuritis, tachycardia). Simultaneous administration of other antituberculosis drugs affecting the CNS, such as isoniazid or cycloserine, can lead to an increase in CNS side effects. The same effect can be caused by simultaneous alcohol intake. In isolated cases, allergic reactions and bone marrow disorders have been described.

Contraindications

Protionamide should not be used in cases of

• Individual hypersensitivity to the drug components;
• During pregnancy and lactation;
• Acute gastritis;
• Peptic ulcer of the stomach and duodenum;
• Erosive-ulcerative colitis;
• Acute hepatitis;
• Liver cirrhosis;
• Chronic alcoholism.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

The drug is contraindicated in liver cirrhosis and acute hepatitis.

Pediatric Use

Children are prescribed at a rate of 10-20 mg/kg of body weight per day.

Geriatric Use

For patients over 60 years of age, the daily dose should not exceed 0.75 g (more often prescribed as 0.25 g 2 times/day).

Special Precautions

Concomitant use of protionamide and alcohol should be avoided due to the risk of central nervous system excitation states (associated with increased toxic effect of alcohol).

When protionamide is used in combination with isoniazid and cycloserine, special attention should be paid to the possibility of mental disorders.

Since the drug is constantly used in combination with other antituberculosis medications, regular monitoring of serum transaminases, gamma-glutamyl transferase and alkaline phosphatase is necessary. In patients with diabetes mellitus, blood sugar levels should be monitored at least once a month.

Skin and especially mucous membrane reactions may be the first signs of pellagra-like side effects. This should be considered a reason for necessary drug withdrawal.

Drug Interactions

During combination therapy for tuberculosis, the additive hepatotoxic effect of individual drugs should be taken into account. This applies especially to the combination of protionamide with isoniazid, rifampicin and pyrazinamide. An additive effect on the central nervous system is noted with the combined use of isoniazid and cycloserine.

Simultaneous alcohol intake leads to an increase in the excitatory effect on the CNS. In certain cases, when taking protionamide, it is necessary to reduce the dose of insulin or oral antidiabetic drugs.

Due to metabolic competition, the conversion in the body of other drugs, for example, isoniazid or barbiturates, is slowed down.

Storage Conditions

List B. The drug should be stored in a dry, cool place, protected from light, out of reach of children.

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the packaging.

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.