Tionamid

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Tionamid

Method of action: Anti-Tuberculosis

Treatment option:

Medically reviewed

Rosario Oropesa

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Tionamid

What is Tionamid? Definitive Overview

Property Description
Active ingredient Protionamide (PTH)
Form Tablet (film-coated or dispersible)
Pharmacological class Antitubercular agent; Thioamide derivative
Common use Part of combination therapy for drug-resistant bacterial infections
Origin Synthetic

Tionamid: Identity, Differentiation, and Active Ingredient

Tionamid is the trade name for a highly specialized medicine whose core component is the active ingredient Protionamide (PTH). This substance is a synthetic chemical compound, typically prepared for oral intake as a tablet. Protionamide is classified chemically as a thioamide derivative related to isonicotinic acid.

Protionamide was developed as a propyl-analogue to the related drug, Ethionamide. This structural modification was intended to potentially improve the drug's tolerability, a factor clinically recognized for its significance in managing long-term treatment adherence. The medicine’s prescription-only status underscores its differentiated role as a high-value reserve agent.


Pharmacological Class and Essential Purpose

Protionamide belongs to the pharmacological class of Anti-infective agents, specifically designated as a crucial second-line Antitubercular agent. Its clinical necessity is reflected in its status as an essential medicine for drug-resistant disease, confirming its strategic importance in global health.

The general purpose of Protionamide is to provide an essential component of combination therapy regimens used to address bacterial infections, primarily those caused by mycobacteria, that have demonstrated resistance to standard initial treatments. The drug acts by interfering with the synthesis of mycolic acids, vital building blocks for the bacterial cell wall, a bacteriostatic effect that helps suppress the progression of the disease.

Regulatory References

  1. WHO Model List of Essential Medicines

What side effects are possible with Tionamid?

Possible side effects and safety information

The safety profile of Tionamid (Protionamide), documented in official regulatory sources, centers on risks to the gastrointestinal, hepatic, and nervous systems. Adverse reactions are classified by frequency and system-organ class.


Adverse Reaction Classifications

Classification Examples of Reactions Affected Systems (SOC)
Very Common Taste changes, anorexia, nausea Gastrointestinal Disorders
Common Headache, dizziness, elevated serum transaminases Nervous System, Hepatobiliary Disorders
Uncommon Vomiting, abdominal pain, psychoses, confusion Gastrointestinal, Psychiatric Disorders
Rare Hypoglycemia, hypothyroidism, convulsive paroxysms Metabolism, Endocrine Disorders

Serious Safety Considerations

Official prescribing information identifies Hepatotoxicity (hepatitis and jaundice) as a serious adverse reaction that may necessitate discontinuation of treatment. Severe neuropsychiatric disturbances, including psychoses, encephalopathy, and optic neuritis, are also explicitly documented as serious concerns.

Safety constraints exist for specific populations. The medicine is contraindicated in patients with severe hepatic impairment and during pregnancy and lactation. Caution and frequent monitoring are required for patients with diabetes mellitus and those with a history of cerebral seizure disorders or psychiatric illnesses. Frequent monitoring of liver and thyroid function is required throughout the course of treatment due to the documented risks associated with prolonged exposure. Furthermore, regulatory documents specify that alcohol should not be consumed during treatment due to the risk of disulfiram-like reactions and increased risk of psychosis.

Overdose and Emergency Response

Overdose and when to seek help

Official regulatory information for Tionamid (Protionamide) focuses on managing the risk of severe toxicity following excessive intake. Suspected overdose is associated with an intensification of the drug’s primary toxic effects on major organ systems, necessitating immediate emergency action.


Documented Overdose Manifestations

System Affected Manifestation Examples
Neurological/CNS Seizures, profound confusion, headache, peripheral neuropathy, and dizziness.
Hepatobiliary Acute hepatotoxicity, including signs of jaundice and significantly elevated liver enzymes.
Metabolic Hypoglycaemia (critically low blood sugar) and hypothyroidism.

Required Emergency Actions

The regulatory guidance states that a patient must contact a healthcare provider or the nearest hospital emergency department for advice immediately upon suspected overdose. Urgent medical attention is required for the onset of life-threatening signs such as seizures or evidence of acute hepatic failure. Treatment is strictly symptomatic and supportive, as no specific chemical antidote is known for Protionamide toxicity. Management includes close hospital monitoring of hepatic function and the administration of pyridoxine (Vitamin B6) to help mitigate the documented neurotoxic effects. The risk of severe toxicity is heightened in patients with pre-existing hepatic impairment.

Therapeutic Uses of Tionamid

What Tionamid Treats: Main Uses and Benefits

Tionamid (Protionamide) is primarily used to treat Tuberculosis (TB) infections that are drug-resistant to standard first-line medications, acting as an essential second-line agent for multidrug-resistant TB (MDR-TB). It is commonly used when first-line agents fail, contributing to the therapeutic support for addressing the active infection caused by these resistant mycobacteria. This application is relevant for patients facing severe, active disease, including those with Extensively Drug-Resistant TB (XDR-TB).


Key Therapeutic Applications

Beyond drug-resistant tuberculosis, Tionamid is commonly used for managing Leprosy (Hansen's Disease) and may be part of symptomatic management for certain non-tuberculous mycobacterial (NTM) infections. Its inclusion in a comprehensive regimen supports the management of the condition and may assist with easing the overall symptom load across the body, offering support when symptoms relate to systemic imbalance. Tionamid may contribute to the overall therapeutic control of the disease and contributes to the management of disease progression in challenging cases.


Quick Fact: Support in Resistant Infection
Supports day-to-day comfort during periods of active, progressive mycobacterial disease.

Eligibility and Restrictions for Use

Tionamid (Protionamide) eligibility is strictly defined by official regulatory documents based on the patient’s clinical status and physiological factors.


Who Must Not Use Tionamid

Use of Tionamid is contraindicated in patients with a history of hypersensitivity to protionamide, other thioamide derivatives, or any of the excipients. It is strictly prohibited in individuals with severe hepatic impairment or acute hepatitis. Furthermore, the medicine is contraindicated for women who are pregnant. Other groups formally prohibited from use include patients diagnosed with cerebral seizure disorders, psychoses, or porphyria.

Populations Requiring Special Consideration

While the medicine is established for use in adults and children, the standard tablet formulation is not suitable for children weighing less than 10 kg, requiring an alternative product. Patients with severe renal impairment require close monitoring for side effects and possible dose reduction. Use is generally not recommended for women who are lactating. Caution is also mandated for patients with diabetes mellitus due to the risk of hypoglycemia and for those with pre-existing psychotic disturbances.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Official regulatory documents define the interaction profile of Tionamid (Protionamide) based on documented pharmacokinetic and pharmacodynamic effects, particularly with other agents used in antitubercular therapy. The profile includes significant constraints and required cautions.


Documented Pharmacological Interactions

Interaction Type Interacting Substances Official Regulatory Outcome
Exposure Modification (PK) Isoniazid Increases the plasma concentration of Protionamide in the blood.
Metabolic (PK) Isoniazid, Barbiturates Protionamide decelerates the degradation of the co-administered drug.
Additive Organ Toxicity (PD) Rifampicin, Pyrazinamide Risk of additive liver-damaging effects (hepatotoxicity).
Additive CNS Effects (PD) Cycloserine, Terizidone Amplification of centrally stimulating or neurotoxic effects.

Other Interactions and Restrictions

Co-administration with P-aminosalicylic acid (PAS) is officially documented to increase the risk of developing hypothyroidism. A key interaction-related restriction is that Alcohol (Ethanol) must be avoided because concomitant intake is documented to amplify the centrally nervous exciting effect, carrying a risk of precipitating a psychotic reaction. Furthermore, Tionamid use is formally contraindicated in patients with severe hepatopathy or acute hepatitis, independent of co-administered medicines.

Mechanism of Action

How Tionamid Works: Mechanism of Action

Tionamid’s action is defined by a mechanism of targeted protein degradation that modulates core immune and cell-survival pathways. It functions as an allosteric modulator that binds to the E3 ubiquitin ligase enzyme Cereblon (CRBN), a critical component of the CRL4^ CRBN complex. This binding event alters CRBN's conformation, transforming the complex into a neo-substrate ligase.

This altered enzyme complex then recruits the transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos) and marks them for destruction via ubiquitination. The subsequent rapid and targeted breakdown of IKZF1 and IKZF3 by the proteasome results in the suppression of anti-apoptotic pathways and the promotion of programmed cell death (apoptosis) in specific cell types. The molecular effects cascade into systemic physiological changes, including immunomodulation and an anti-angiogenic effect, resulting in the suppression of inflammation- and proliferation-associated signaling.

Dosage and Administration Information

How to Use Tionamid (Protionamide)

Tionamid is administered exclusively via the oral route as a 250 mg tablet and must be integrated into a combination drug regimen as prescribed by a specialist. The medicine's use is structured by established dosing and timing principles to ensure standardized administration.


Standard Administration Principles

Adult dosing is determined by body weight, typically ranging from 15 mg/kg per day to 20 mg/kg per day. The total daily dose is strictly limited and must not exceed 1,000 mg (1 gram). This regimen is usually administered once daily, although a schedule of two or three divided doses per day may be adopted to improve patient tolerability.

Treatment initiation follows a gradual dose escalation. The starting dose is usually 250 mg once daily, and the amount is increased by 250 mg increments every three to five days until the prescribed target dose is reached. The medicine must be consumed with or immediately following a meal to minimize common gastrointestinal effects.


Special Dosage Conditions

A critical instruction for the proper use of Tionamid is the mandatory co-administration of Pyridoxine (Vitamin B6). Dosing adjustments are required for certain populations: patients with severe renal impairment typically require a reduction to a total daily dose between 250 mg and 500 mg. Furthermore, when Tionamid is used concurrently with the drug Isoniazid, the maximum daily dose is reduced to 500 mg. Pediatric dosing is also weight-based but maintains a separate, specified maximum daily limit. The overall duration of use follows the phases of the combination treatment protocol, encompassing an initial intensive phase and a continuation phase.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Tionamid

Evidence for Use in Multidrug-Resistant Tuberculosis (MDR-TB)

Research exploring Tionamid as a component for Multidrug-Resistant Tuberculosis (MDR-TB) has centered on large-scale international clinical trials and observational cohort studies. These studies included adult patients with TB that was associated with resistance to standard first-line drugs. Researchers examined key outcomes, such as the definition of treatment success and the time required for sputum culture conversion (a measure of bacterial clearance).

These studies describe patterns observed in the patient populations, focusing on how measured outcomes were recorded under various combination regimens. Research explored how patients receiving Protionamide as part of their regimen compared to groups observed in regimens with different components. The individual contribution of Protionamide to the overall outcome is often difficult to isolate because it is studied alongside multiple other drugs.


Evidence for Use in Leprosy (Hansen's Disease)

The research landscape for Tionamid's role in Leprosy is characterized by older historical clinical trials and cohort studies. These studies explored short-term symptom changes, often focusing on the drug's activity either alone (monotherapy) or as part of early combination schemes. However, this evidence does not reflect modern standard practice.


What is Still Uncertain About Tionamid Research

Evidence quality varies across studies, ranging from large, standardized cohort data for MDR-TB to small-scale, historical, or laboratory-based reports for other indications. Certainty remains low regarding the drug’s exact, independent contribution to the success of MDR-TB regimens. Furthermore, comparative evidence is lacking for many potential substitution scenarios. Because the drug is reserved for use in specialized, second-line regimens, there is limited information available for populations such as children and older adults.

Key Studies & References

  1. A review of the use of ethionamide and prothionamide in childhood tuberculosis
  2. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline
  3. The selection and use of essential medicines: WHO Model List of Essential Medicines, 24th list, 2025
  4. Joint Chemotherapy trials in lepromatous leprosy conducted in Thailand, the Philippines, and Korea

Frequently Asked Questions (FAQ)

Common questions about Tionamid (FAQ)

Q: What kind of symptoms is Tionamid intended to help manage?

A: Tionamid is an anti-bacterial agent used as a crucial component of a combination therapy regimen for drug-resistant tuberculosis (TB). Official information indicates the full regimen is used to address the bacterial infection associated with symptoms like persistent cough, fever, night sweats, and weight loss.

Q: Is it possible for the effects of Tionamid to decrease over time?

A: Regulatory information concerning anti-bacterial agents indicates that the risk of developing resistance is a known concern mentioned in the context of TB treatment. To help prevent this, Tionamid is typically used alongside other medications as part of a combination regimen.

Q: Are there specific laboratory tests required while taking Tionamid?

A: Yes, official prescribing information describes the requirement for frequent monitoring of certain bodily functions. This includes regular checks of liver function (such as serum transaminases) and thyroid function. Eye exams may also be recommended by a healthcare provider.

Q: Can taking Tionamid cause unusual tiredness or fatigue?

A: Official product information lists drowsiness and weakness as common possible side effects. A patient may experience these symptoms as a feeling of unusual tiredness or fatigue.

Q: Can Tionamid be prescribed to patients who have kidney problems?

A: Official documents advise caution for patients with kidney impairment. In cases of severe renal impairment, a lower dose is typically required, and close monitoring is mandated.

Q: Can Tionamid be linked to changes in a person's mood, anxiety, or mental state?

A: Official documents list effects on the nervous and psychiatric systems. Uncommon side effects include confusion, psychoses, and changes in mood such as depressive reactions. Patients with a history of psychiatric illness are described as needing special caution and monitoring.

Q: Does Tionamid affect appetite or weight change?

A: Official prescribing information lists loss of appetite (anorexia) as a very common side effect of the medicine. While anorexia is listed, weight change itself is not explicitly listed as a primary adverse reaction.

Q: Are there any studies or official documents detailing the use of Tionamid in children or adolescents?

A: Official documents indicate the medicine is established for use in adults and children. However, the standard tablet form is not suitable for children weighing less than 10 kg, which requires an alternative product formulation.

Q: Is it safe to take Tionamid if I have a history of diabetes?

A: Caution is described for patients with diabetes mellitus. This is due to a documented risk of hypoglycemia (reduced blood sugar levels). Close monitoring of blood glucose levels is specified in the safety information.

Q: Does Tionamid affect the senses of taste or smell?

A: Official product information lists a metallic or sulfur taste as a very common side effect. The side effect profile does not explicitly list effects on the sense of smell.

Q: Is experiencing dizziness or lightheadedness a normal expectation when starting Tionamid?

A: Regulatory documents list dizziness as a common side effect of the medicine. If dizziness or lightheadedness occurs, regulatory information advises avoiding activities that require high alertness, such as driving or operating heavy machinery.

Q: Do the common side effects associated with Tionamid tend to improve or go away over time?

A: Official patient information indicates that most side effects are considered temporary and may gradually lessen over time as the body adjusts to the medicine. If any side effects persist or worsen, it is important to consult your healthcare provider.

Q: Can Tionamid cause changes in sleep patterns?

A: Official regulatory documents list sleep disorders (such as difficulty sleeping or insomnia) as a rare side effect of the medicine.

Q: Should Tionamid be taken with or without food, and does it matter?

A: Official administration instructions state that Tionamid must be taken with or immediately following a meal. This practice is advised to help minimize common gastrointestinal side effects like nausea and vomiting.

Q: Are there any foods or beverages that should be avoided while taking Tionamid?

A: Regulatory documents describe that Alcohol (Ethanol) must be avoided during treatment. Furthermore, it is recommended to avoid foods and drinks that are high in histamine or tyramine, such as certain aged cheeses, cured meats, and wines.

Q: Are there any expected side effects that should be reported to a healthcare provider?

A: Symptoms of serious adverse reactions are described as needing immediate reporting to a healthcare provider. These include signs like blurred vision, confusion, dark urine, and yellowing of the skin or eyes (jaundice).

Q: What is known about the use of Tionamid during pregnancy?

A: Official information generally advises that the medicine is contraindicated (strictly prohibited) during pregnancy due to documented potential risks to the fetus. It is generally described as being only considered when the expected benefits are determined to outweigh the potential risks.

Q: Is Tionamid suitable for patients with a history of low blood pressure?

A: Official side effect lists include orthostatic hypotension (a sudden drop in blood pressure when standing) as a potential effect. Individuals with a history of low blood pressure should consult their doctor for caution.

Q: Can Tionamid be used by elderly patients, and are there special considerations for this group?

A: Caution is advised for elderly patients. Official documents note that side effects like dizziness and lightheadedness may occur more commonly or severely in this group. Extra care is specified to avoid falls.

Q: Can Tionamid be taken at the same time as antacids or calcium supplements?

A: Official guidance states that antacids, particularly those containing aluminum, should be taken at least four hours before or after Tionamid to prevent interactions that affect absorption. You should consult your doctor regarding the simultaneous use of iron or calcium supplements.

Q: What happens if I miss a scheduled dose of Tionamid?

A: Official patient information addresses missed doses. Due to the requirement for a precise regimen, specific guidance on managing a missed dose is often obtained directly from a healthcare provider or pharmacist.

Q: Is Tionamid intended to "cure" a condition or just manage symptoms?

A: Tionamid is defined as a bacteriostatic agent, meaning it helps stop the growth of bacteria. It is used as a vital component of a combination therapy regimen, and the goal of the full regimen is to eliminate the bacterial infection and achieve treatment success.

Q: Are there any known age restrictions for taking Tionamid?

A: The medicine is authorized for use in adults and children, but the standard tablet formulation is not suitable for children weighing less than 10 kg. Use in any child requires specialist consultation.

Q: What kind of general lifestyle considerations are often mentioned for people taking Tionamid?

A: Official documents include lifestyle considerations such as avoiding alcohol and potentially avoiding certain foods high in histamine or tyramine. Maintaining adequate hydration is also often advised.

Q: What should I do if Tionamid makes me too sleepy?

A: If you experience significant dizziness or drowsiness, regulatory information advises avoiding activities that require high alertness, such as driving or operating heavy machinery. It is important to consult a healthcare provider if these effects persist.

Q: Is Tionamid suitable for patients with a history of cerebral seizure disorders?

A: No, official regulatory documents state that the medicine is contraindicated (strictly prohibited) for patients with a history of cerebral seizure disorders.

How should Tionamid be stored and disposed of?

How to Store and Dispose of Tionamid (Protionamide)

Official regulatory documents define strict conditions for storing and disposing of Tionamid tablets, whose active ingredient is Protionamide.


Storage Requirements

The medicine must be stored at a temperature not exceeding 30°C and must be protected from light. To ensure light protection, tablets should remain inside their original blisters and the outer carton. The product has a labeled shelf life of 36 months when stored correctly. The medicine must always be kept out of the sight and reach of children.


Disposal Instructions

There are no special handling requirements beyond standard procedures. Any unused or expired product must be disposed of in accordance with local requirements for pharmaceutical waste.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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