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Prothionamide (Tablets) Instructions for Use

ATC Code

J04AD01 (Protionamide)

Active Substance

Protionamide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

Second-line antituberculosis agent. It acts bacteriostatically by blocking the synthesis of mycolic acids, which are a key structural component of the mycobacterial cell wall.

It has the properties of a nicotinic acid antagonist. In high concentrations, it disrupts microbial protein synthesis and acts bactericidally.

It is 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 Cmax 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

Protionamide is used for the treatment of all forms of tuberculosis, including cases with pathogen resistance to other antituberculosis drugs (first-line) or intolerance to them.

ICD codes

ICD-10 code Indication
A15 Respiratory tuberculosis, bacteriologically and histologically confirmed
A17 Tuberculosis of nervous system
A18 Tuberculosis of other organs
ICD-11 code Indication
1B10.0 Respiratory tuberculosis, bacteriologically or histologically confirmed
1B11.Z Tuberculosis of nervous system, unspecified
1B12 Tuberculosis of other systems and organs

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Administer orally after meals to minimize gastrointestinal adverse effects.

For adults, the standard regimen is 0.25 g three times daily.

With good tolerance, increase the dose to 0.5 g twice daily for improved adherence.

For patients over 60 years of age or with a body weight under 50 kg, the maximum daily dose is 0.75 g.

Prescribe this geriatric and low-weight population 0.25 g twice daily as the typical regimen.

For pediatric patients, calculate the dose based on 10-20 mg per kg of body weight per day.

Divide the total daily pediatric dose into two or three administrations.

Always use prothionamide as part of a multidrug regimen to prevent the development of resistance.

Initiate therapy at the lower end of the dosage range and titrate based on patient tolerance.

Discontinue treatment if severe hepatotoxicity or pellagra-like skin reactions occur.

Adverse Reactions

Adverse effects of protionamide manifest from the gastrointestinal tract, liver, skin, endocrine and nervous systems.

From the digestive system: loss of appetite, nausea, vomiting, dry mouth or hypersalivation, metallic taste in the mouth. After drug withdrawal, these phenomena, as a rule, quickly disappear. Often during treatment, an increase in transaminase levels is noted. Rarely, pronounced liver function disorders with signs of hepatitis and jaundice are observed. The hepatotoxicity of the drug depends on existing liver function impairments, such as liver damage due to alcoholism or after surgical interventions. These side effects are noted especially during combined therapy with isoniazid, rifampicin, and pyrazinamide.

From the skin: rarely noted, in isolated cases pellagra-like reactions have been described, corresponding to a combination of skin manifestations and CNS disorders.

From the endocrine system: alongside the development of hypoglycemia (blood glucose 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).

From the CNS: cases of polyneuropathy have been described in combination with isoniazid. Protionamide intake can cause dizziness, headaches, weakness, impaired concentration, and mental disorders. Rarely – optic neuritis, tachycardia. Concurrent use of other antituberculosis drugs affecting the CNS, such as isoniazid or cycloserine, may 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

  • Gastric and duodenal ulcer;
  • Acute gastritis;
  • Erosive-ulcerative colitis;
  • Acute hepatitis;
  • Liver cirrhosis;
  • Chronic alcoholism;
  • Pregnancy;
  • Lactation period;
  • Individual hypersensitivity to the drug components.

With caution – diabetes mellitus, severe hepatic insufficiency.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

With caution – severe hepatic insufficiency. Contraindicated in acute hepatitis and liver cirrhosis.

Pediatric Use

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

Geriatric Use

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).

Special Precautions

Avoid concurrent use of protionamide and alcohol due to the risk of CNS depression (associated with increased toxic effect of alcohol).

During combined use of protionamide 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-glutamyltransferase, and alkaline phosphatase is necessary.

In patients with diabetes mellitus, blood glucose 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 combined tuberculosis therapy, the additive hepatotoxic effect of individual drugs should be taken into account. This especially applies to the combination of protionamide with isoniazid, rifampicin, and pyrazinamide.

An additive effect on the CNS is noted with the combined use of isoniazid and cycloserine.

Concurrent alcohol intake leads to CNS depression.

In certain cases when taking protionamide, it may be necessary to reduce the dose of insulin or oral antidiabetic drugs.

Shelf Life

Shelf life – 4 years. The drug should be stored at a temperature up to 30°C (86°F) in a place protected from light and out of reach of children.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

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.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Marketing Authorization Holder

Lok-Beta Pharmaceuticals (India), Private Limited (India)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets, 250 mg: 10, 20, 30, 40, 50, or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, round, biconvex; the core is yellow on the cross-section.

1 tab.
Protionamide 250 mg

Excipients : lactose monohydrate – 14.5 mg, calcium hydrogen phosphate – 15 mg, povidone K-30 – 5 mg, hypromellose – 2.5 mg, corn starch – 8 mg, microcrystalline cellulose (type PH-102) – 6 mg, talc – 3 mg, crospovidone – 3 mg, magnesium stearate – 2 mg.

Film coating composition: hypromellose — 3.5 mg, titanium dioxide – 1.48 mg, quinoline yellow dye – 0.5 mg, macrogol 6000 – 0.188 mg, macrogol 400 – 0.333 mg.

10 pcs. – PVC/aluminum foil blisters (1) – cardboard packs.
10 pcs. – PVC/aluminum foil blisters (2) – cardboard packs.
10 pcs. – PVC/aluminum foil blisters (3) – cardboard packs.
10 pcs. – PVC/aluminum foil blisters (4) – cardboard packs.
10 pcs. – PVC/aluminum foil blisters (5) – cardboard packs.
10 pcs. – PVC/aluminum foil blisters (10) – cardboard packs.

Marketing Authorization Holder

Lupin, Ltd. (India)

Dosage Form

Bottle Rx Icon Protionamide Coated tablets, 250 mg: 50, 100, 500, 1000, or 3000 pcs.

Dosage Form, Packaging, and Composition

Coated tablets 1 tab.
Protionamide 250 mg

100 pcs. – polyethylene bags (1) – plastic jars.
1000 pcs. – polyethylene bags (1) – plastic jars.
500 pcs. – polyethylene bags (1) – plastic jars.
50 pcs. – polyethylene bags (1) – plastic jars.
50 pcs. – polyethylene bags (1) – polyethylene jars.
3000 pcs. – polyethylene bags (1) – plastic jars.

Marketing Authorization Holder

Lupin, Ltd. (India)

Labeled By

LUPIN, Ltd. (India)

Dosage Form

Bottle Rx Icon Protionamide Coated tablets, 250 mg: 50, 100, 500, 1000, or 3000 pcs.

Dosage Form, Packaging, and Composition

Coated tablets 1 tab.
Protionamide 250 mg

100 pcs. – polyethylene bags (1) – plastic jars.
1000 pcs. – polyethylene bags (1) – plastic jars.
500 pcs. – polyethylene bags (1) – plastic jars.
50 pcs. – polyethylene bags (1) – plastic jars.
50 pcs. – polyethylene bags (1) – polyethylene jars.
3000 pcs. – polyethylene bags (1) – plastic jars.

Marketing Authorization Holder

Simpex Pharma, Pvt. Ltd. (India)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets, 250 mg: 50, 100, 500, or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets 1 tab.
Protionamide 250 mg

10 pcs. – contour cell packs (5) – cardboard packs.
50 pcs. – polyethylene bags (1) – plastic bottles.
10 pcs. – contour cell packs (10) – cardboard packs.
10 pcs. – contour cell packs (50) – cardboard packs.
10 pcs. – contour cell packs (100) – cardboard boxes.
10 pcs. – contour cell packs (500) – cardboard boxes.
500 pcs. – polyethylene bags (1) – plastic bottles.
1000 pcs. – polyethylene bags (1) – plastic bottles.

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon, LLC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets, 250 mg: 10, 20, 30, 40, 50, 100, 150, 200, 250, 500, or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, round, biconvex; on the break, two layers are visible – a yellow core and a film coating.

1 tab.
Protionamide 250 mg

Excipients : microcrystalline cellulose 58.5 mg, hyprolose 8 mg, sodium carboxymethyl starch 12 mg, water 4 mg, povidone 14 mg, sodium stearyl fumarate 3.5 mg.

Film coating composition: hypromellose 5.95 mg, macrogol-4000 1.4 mg, titanium dioxide 2.5 mg, quinoline yellow dye 0.15 mg.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (4) – cardboard packs.
10 pcs. – contour cell packs (5) – cardboard packs.
10 pcs. – contour cell packs (10) – cardboard packs.
50 pcs. – contour cell packs (1) – cardboard packs.
50 pcs. – contour cell packs (2) – cardboard packs.
50 pcs. – contour cell packs (3) – cardboard packs.
50 pcs. – contour cell packs (4) – cardboard packs.
50 pcs. – contour cell packs (5) – cardboard packs.
50 pcs. – contour cell packs (10) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
40 pcs. – polymer jars (1) – cardboard packs.
50 pcs. – polymer jars (1) – cardboard packs.
100 pcs. – polymer jars (1) – cardboard packs.
1000 pcs. – polymer jars (1) – cardboard packs.

Marketing Authorization Holder

Academician V.P. Filatov Plant, LLC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Coated tablets, 250 mg: 50, 100, 1000, 2000, or 2500 pcs.

Dosage Form, Packaging, and Composition

Coated tablets yellow, round, biconvex.

1 tab.
Protionamide 250 mg

Excipients : povidone, starch, colloidal silicon dioxide (anhydrous), purified talc, magnesium stearate, sodium croscarmellose.

Coating composition hypromellose, titanium dioxide, purified talc, diethyl phthalate, quinoline yellow.

10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (200) – cardboard packs.
1000 pcs. – polyethylene bags (1) – plastic jars.

Marketing Authorization Holder

Technology Lekarstv LLC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets, 250 mg: 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets 1 tab.
Protionamide 250 mg

10 pcs. – contour cell packs (10) – plastic jars
10 pcs. – contour cell packs (5) – plastic jars
100 pcs. – polymer jars (1) – cardboard packs
50 pcs. – polymer jars (1) – cardboard packs.

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets 250 mg: 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, biconvex in shape; the cross-section of the tablet is yellow.

1 tab.
Protionamide 250 mg

Excipients: microcrystalline cellulose – 38.5 mg, potato starch – 3 mg, magnesium stearate – 1.5 mg, lactose monohydrate – 35.5 mg, colloidal silicon dioxide (aerosil, grade A300) – 3.3 mg, kollidon – 11 mg, sodium starch glycolate – 7.2 mg. The mass of the uncoated tablet is 350 mg.

Film coating composition: ready-made film coating – 10 mg (composition: hypromellose – 66%, titanium dioxide – 24.07%, glyceryl caprylocaprate – 9%, yellow iron oxide dye – 0.23%, quinoline yellow aluminum lake – 0.7%). The mass of the coated tablet is 360 mg.

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

Marketing Authorization Holder

Pharmconcept, LLC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Film-coated tablets, 250 mg: 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow in color, round, biconvex; the core on the cross-section is yellow.

1 tab.
Protionamide 250 mg

Excipients: microcrystalline cellulose type 101 – 10.5 mg, corn starch – 49 mg, magnesium stearate – 3.5 mg, lactose monohydrate – 30 mg, colloidal silicon dioxide – 7 mg.

Tablet coating ready-made mixture “Vivacoat PA-2P-000” (hypromellose – 3.9 mg, titanium dioxide – 2.5 mg, polydextrose – 1.5 mg, talc – 1 mg, macrogol – 0.6 mg, yellow iron oxide dye – 0.5 mg).

10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard boxes (for hospitals).
10 pcs. – contour cell packaging (10) – cardboard boxes (for hospitals).
50 pcs. – jars (1) – cardboard boxes (for hospitals).
100 pcs. – jars (1) – cardboard boxes (for hospitals).
150 pcs. – jars (1) – cardboard boxes (for hospitals).

Marketing Authorization Holder

Fortune Med, LLC (Russia)

Manufactured By

Lincoln Pharmaceuticals, Ltd. (India)

Packaging and Quality Control Release

LINCOLN PHARMACEUTICALS, Ltd. (India)

Or

INTERPHARMA, LLC (Russia)

Dosage Form

Bottle Rx Icon Protionamide Coated tablets, 250 mg: 50, 100, or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow in color, round, biconvex, smooth on both sides; the color of the tablet at the break is yellow.

1 tab.
Protionamide 250 mg

Excipients: corn starch – 34 mg, colloidal silicon dioxide – 2 mg, croscarmellose sodium – 6 mg, magnesium stearate – 4 mg, povidone – 10 mg, talc – 4 mg, coating – quinoline yellow dye.

10 pcs. – blisters (5) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
10 pcs. – blisters (100) – cardboard packs.

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