Metacardia MR

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Overview of Metacardia MR

Quick Facts

Property Description
Active ingredient Trimetazidine dihydrochloride
Form Modified-Release Tablet (MR)
Pharmacological class Cytoprotective Anti-Ischemic Agent, Metabolic Agent
Common use Symptomatic support for stable angina pectoris
Origin Synthetic (Piperazine derivative)

What Type of Medicine is Metacardia MR (Trimetazidine)?

Metacardia MR is a pharmaceutical preparation containing the active ingredient Trimetazidine dihydrochloride, a synthetic compound derived from piperazine. It is primarily categorized as a metabolic agent because its effect is achieved by modulating how heart cells produce energy, rather than by altering blood pressure or heart rate.

This specific action places it within the ATC classification code C01EB15, which denotes it as an “Other cardiac preparation.” The non-hemodynamic nature of Trimetazidine is a key differentiating feature that distinguishes it from traditional anti-anginal drugs.


What is the Purpose of a Metabolic Agent in Cardiac Care?

The general purpose of the metabolic agent Trimetazidine is to maintain the functional integrity of the heart muscle cells when they are under the stress of inadequate oxygen supply. This is achieved by promoting an energy shift within the cardiac cells, causing them to favor the consumption of glucose over fatty acids.

Trimetazidine acts by enhancing glucose oxidation, which optimizes cellular energy processes in ischemic conditions. This leads to overall oxygen optimization, which helps the heart muscle work more efficiently and protects it against stress. This property makes it valuable for the symptomatic treatment of stable angina pectoris.


Understanding the Modified-Release Tablet (MR) Form

The medication is formulated as a Modified-Release Tablet (MR), which is a specialized oral solid dosage form. The MR designation is central to the drug’s identity, as it ensures the slow, steady liberation of Trimetazidine into the body over an extended duration. The active substance is a piperazine derivative. This continuous, sustained action provides consistent, reliable cytoprotective support throughout the day.

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What side effects are possible with Metacardia MR?

Official Safety Profile and Adverse Reactions

Medicines containing Trimetazidine dihydrochloride (Metacardia MR) are associated with a documented safety profile derived from clinical trials and post-marketing surveillance, as classified by regulatory authorities like the European Medicines Agency (EMA).

Adverse reactions are grouped by the body system affected and frequency of occurrence:

Frequency System Organ Class (SOC) Examples of Documented Effects
Common (up to 1 in 10) Nervous System, Gastrointestinal, Skin, General Disorders Dizziness, headache, abdominal pain, nausea, vomiting, diarrhoea, rash, pruritus, asthenia (weakness)
Rare (up to 1 in 1,000) Vascular, Cardiac Orthostatic hypotension (low blood pressure upon standing, associated with a risk of falls), palpitations, tachycardia
Not Known Nervous System, Blood, Hepatobiliary Parkinsonian symptoms (tremor, gait instability, akinesia, hypertonia), agranulocytosis, hepatitis, angioedema

Serious Adverse Reactions and Safety Constraints

The regulatory safety information highlights specific, clinically significant reactions and patient constraints.

Parkinsonian symptoms are a serious adverse reaction of Not Known frequency. These movement disorders (including tremor and gait instability) have been documented as typically reversible following the definitive withdrawal of treatment.

Safety constraints apply to specific populations. The use of Trimetazidine is contraindicated in individuals with pre-existing Parkinson's disease or other movement disorders, and in patients with severe renal impairment (creatinine clearance < 30 mL/min). Caution is specifically advised for older adults (over 75 years old) and patients with moderate renal impairment.

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Overdose and Emergency Response

Overdose and When to Seek Help

The information available regarding overdose of the active ingredient, Trimetazidine dihydrochloride, is limited in official regulatory documents. Authorities note that very limited information is available concerning the specific clinical manifestations, signs, or symptoms of an acute overdose in patients.


Official Regulatory Requirements

Requirement Official Statement Basis
Clinical Information Very limited data available on specific overdose symptoms.
Antidote No specific antidote is documented in the official prescribing information.
Management Treatment is officially required to be strictly symptomatic and supportive.

When Urgent Medical Help is Required

In the event that more than the recommended dose of Metacardia MR is taken, official guidance mandates that patients or caregivers must seek medical advice immediately.

Regulatory authorities require that a doctor or the nearest hospital Emergency Department immediately be contacted. This immediate action is necessary to ensure that appropriate symptomatic and supportive treatment, as required by the prescribing information, is initiated without delay. No specific population-based considerations (e.g., for elderly or renally impaired patients) regarding overdose severity are documented in the official overdose sections.

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Therapeutic Uses of Metacardia MR

Quick Facts on Metacardia MR

  • May be used to assist in the management of stable angina pectoris.
  • Intended for the symptomatic treatment of chest discomfort.
  • May be an appropriate option when first-line therapies are not tolerated or do not provide adequate control.

Metacardia MR contains trimetazidine, a medication primarily prescribed as an adjunct therapy for the symptomatic treatment of stable angina pectoris. Angina pectoris is a condition that involves chest pain or discomfort due to reduced blood flow to the heart muscle. The medication may be a therapeutic choice for patients whose symptoms are not sufficiently managed by, or who are intolerant to, initial anti-anginal agents.

Metacardia MR is used to help reduce the frequency of anginal attacks and decrease the need for rescue medication containing nitrates. By supporting the heart muscle's function under periods of reduced oxygen supply, this treatment assists in managing associated symptoms. Its use is restricted to stable angina management when other primary treatments are inadequate or unsuitable.

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Eligibility and Restrictions for Use

Who Can and Cannot Use Metacardia MR (Trimetazidine)

Official regulatory documents define strict population eligibility for Metacardia MR, focusing primarily on age, organ function, and pre-existing neurological conditions.

Contraindications and Prohibitions

Metacardia MR is contraindicated in several specific populations, meaning these individuals must not use the medicine:

  • Patients with hypersensitivity to Trimetazidine dihydrochloride or any of the excipients.
  • Individuals diagnosed with Parkinson disease, parkinsonian symptoms, tremors, or restless leg syndrome.
  • Patients suffering from severe renal impairment (creatinine clearance less than 30 ml/min).

Restricted and Non-Recommended Use

Population Regulatory Status
Children & Adolescents (< 18 yrs) Not recommended; safety and efficacy have not been established.
Moderate Renal Impairment Use requires caution and a specific dose adjustment.
Elderly Patients (> 75 yrs) Use requires caution due to potential age-related decline in kidney function.
Pregnancy Preferable to avoid due to insufficient clinical data.
Breastfeeding Not recommended.

Metacardia MR is officially permitted for use only in the adult population (18 years and older) who do not fall into any of the contraindicated or restricted groups.

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What should I know about interactions with other medicines?

Interactions with other medicines and products

This section describes the officially documented interactions for the active substance trimetazidine (Metacardia MR), focusing strictly on information found in authoritative governmental regulatory documents.

The primary concern relates to Pharmacodynamic Interactions that can affect the central nervous system and movement control.


Documented Interaction Profile

Interacting Product Category Specific Interacting Medicine Regulatory Restriction
Agents causing Extrapyramidal Symptoms Levodopa (L-dopa) Combination is not recommended or avoided
Other Dopaminergic Agonists None explicitly listed in this class Use with caution

The official documentation explicitly states that the combination with Levodopa (L-dopa) must be avoided due to the increased risk of developing or worsening movement disorders, such as extrapyramidal symptoms or gait disturbances. The interaction is classified as a significant restriction based on pharmacodynamic synergy.

Pharmacokinetic Considerations

Metacardia MR has a low potential for pharmacokinetic interactions with other medicines because the active substance, trimetazidine, is primarily eliminated from the body unchanged via the kidneys and involves minimal metabolism by liver enzymes. Therefore, it is not subject to broad interactions with medicines that are strong inhibitors or inducers of Cytochrome P450 (CYP) enzymes. However, constraints related to elevated drug exposure are noted for patients with severe renal impairment, requiring careful consideration when co-administering any other substance in this population.

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Mechanism of Action

Modulation of Myocardial Energy Metabolism

Metacardia MR (trimetazidine) acts as a selective metabolic agent that targets the mitochondrial energy production pathway within cardiomyocytes. Its mechanism involves the inhibition of the enzyme long-chain 3-ketoacyl-CoA thiolase (3-KAT), which is essential for the final step of fatty acid beta-oxidation. This enzymatic action results in a primary shift of the heart's energy substrate utilization from fatty acids toward glucose oxidation. This metabolic redirection influences the cell's oxygen consumption rate, supporting the maintenance of cellular ATP generation capacity in states of reduced oxygen availability.

Influence on Cellular Homeostasis

The drug exerts an intracellular cytoprotective effect, helping to maintain the stability of mitochondria and cell membranes. This includes modulating the intracellular balance of ions, particularly reducing calcium overload, and increasing the cell's capacity to neutralize reactive oxygen species (ROS). These actions influence subsequent myocardial contractile and relaxation dynamics and modulate the cellular injury processes initiated by oxygen deprivation, thereby affecting the mechanical and electrical properties of the tissue.

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Dosage and Administration Information

How Metacardia MR is Used: Administration Guidelines

Metacardia MR, a modified-release tablet formulation of trimetazidine, is administered via the oral route. Its use is structured around a precise dosing schedule and specific conditions to ensure proper action.

Standard Adult Regimen

The standard adult dose is one 35 mg tablet taken twice daily, which provides a total daily dose of 70 mg. The schedule involves one dose in the morning and one dose in the evening. The administration occurs during meals. To maintain the modified-release profile, tablets are swallowed whole and are not to be crushed, split, or chewed.

Procedural Instructions and Time-Based Review

If a dose is missed, the next scheduled dose is taken at the usual time; a double dose is not taken to compensate for the forgotten one. The benefit of continuing the treatment is assessed after three months of use, and administration ceases if there is no observed response.

Population-Specific Dosing

Specific dosage adjustments exist for certain groups:

  • Moderate Renal Impairment: For patients with moderate renal impairment (creatinine clearance 30 to 60 mL/min), the regimen is one 35 mg tablet once daily, taken in the morning during breakfast.
  • Older Adults: Dose adjustment follows the same criteria as moderate renal impairment. Caution is applied when initiating or adjusting the dose in this population.
  • Pediatric Population: The safety and efficacy of trimetazidine in patients below 18 years of age have not been established, and its use in this population is therefore not recommended.
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Recent Clinical Evidence

Research Evidence / Overview of Studies for Metacardia MR (Trimetazidine)

The research concerning Metacardia MR (Trimetazidine) has primarily focused on its clinical evaluation for stable angina pectoris. The evidence was evaluated in numerous clinical trials investigating stable angina pectoris, which contribute to the broader evidence landscape used by regulatory bodies.


## Evidence for Use in Stable Angina Pectoris

This section summarizes the design and scope of the core randomized controlled trials (RCTs) and systematic reviews that examined the use of Metacardia MR as an add-on therapy for stable angina pectoris. The content details the clinical and functional outcomes that were measured in these trials, which are relevant in trials assessing short-term or episodic symptom patterns.

The majority of studies examined use in patients whose outcomes related to physical discomfort and exercise capacity were being monitored while they were already receiving other anti-anginal medications. These trials were typically short-term, lasting from a few weeks up to about six months. Researchers monitored how symptoms evolved in the observed populations by tracking the weekly frequency of angina attacks and the amount of short-acting nitrate medication used by patients for relief.

The clinical findings suggest patterns where the addition of this medicine was associated with measured differences in the reported frequency of angina episodes and the consumption of rescue nitrates, compared to adding a placebo. Functional capacity was also evaluated in studies using standardized exercise tests, where data show measured changes in the onset of objective signs of ischemia and differences in total exercise duration.


## Long-Term Studies and Follow-Up Data

The research exploring short-term symptom changes is the prevailing type compared to studies focusing on long-term survival or major cardiac events. While some larger, randomized trials were observed in patients over extended time intervals, these studies monitored what are called hard endpoints, such as cardiac death or non-fatal heart attack.

Based on the scientific literature, the evidence is limited regarding the medicine's association with a reduced risk of these major long-term adverse cardiac events in the general stable angina population. Because of this, the regulatory emphasis on the available evidence is centered on symptomatic control and quality of life rather than on long-term cardiac event influence.


## Evidence Quality, Limitations, and Research Gaps

Regulatory bodies have noted that evidence quality varies across studies, and some of the earlier research was observed in only modest sample sizes or contained methodological weaknesses. The most significant research gap remains the lack of consistent evidence from long-term, large-scale trials exploring a consistent influence on major adverse cardiac events for the general stable angina population. This means the research provides context regarding short-term changes and symptom patterns, but there is limited information for long-term outcomes regarding overall cardiac function.

Key Studies & References

  1. Trimetazidine as Adjunctive Therapy for Decreasing Major Adverse Cardiac Events in Coronary Artery Disease Patients Undergoing Reperfusion
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Frequently Asked Questions (FAQ)

Common questions about Metacardia MR (FAQ)


Q: Can Metacardia MR be used for anxiety or panic attacks?

Metacardia MR is a prescription medicine that is indicated for use in a specific condition. According to regulatory documents, its sole therapeutic use is as an add-on treatment for the symptomatic support of adults with stable angina pectoris. The official product information does not list uses for conditions like anxiety or panic attacks.


Q: What are the most commonly reported long-term side effects of Metacardia MR?

Official regulatory safety documents report adverse effects by frequency (common, rare, not known). These documents do not currently provide separate frequency data distinguishing between the incidence of common side effects in the short-term versus the long-term. You can find a complete list of all documented adverse reactions in the 'Possible side effects and safety information' section.


Q: Can I stop taking Metacardia MR once I feel better?

The decision to continue the medicine is based on a review by a healthcare professional after a specific period of use. Regulatory documents state that the benefit of continued treatment must be formally assessed after three months. If a beneficial response is not observed, the administration of the medicine may cease.


Q: What are the known interactions between Metacardia MR and common painkillers like ibuprofen?

Official regulatory documentation lists specific medicine interactions, primarily with drugs that affect movement. While general non-prescription painkillers are not explicitly listed, the medicine is noted as having a low potential for pharmacokinetic interactions with many other substances. This is because the active ingredient is mainly eliminated unchanged via the kidneys.


Q: Are there any dietary restrictions while using Metacardia MR?

The only official instruction regarding consumption relates to taking the medicine with meals. Regulatory documents specify that Metacardia MR should be taken during meals. No other specific food or beverage restrictions are listed in the official product information.


Q: Do the side effects of Metacardia MR usually go away after a while?

For certain serious adverse reactions, regulatory information states that they are typically reversible. Specifically, movement disorders known as Parkinsonian symptoms have been documented as resolving after the definitive withdrawal of the medicine. For common side effects like headache or nausea, official product documents do not specify a timeframe for resolution.


Q: What is the research evidence for using Metacardia MR in patients over 65?

Official guidance specifies that age-related decline in kidney function must be considered by a prescriber for older patients (over 75 years old), requiring caution in this group. The drug's official research evidence focuses on symptomatic control within the general adult population.


Q: Is Metacardia MR considered a safe option for long-term treatment?

The regulatory emphasis on the available evidence is centered on symptomatic control and quality of life. The official treatment protocol states that the medicine's benefit must be assessed after three months. Research has been limited regarding the medicine's influence on major cardiac events over extended periods in the general stable angina population.


Q: Is it true that Metacardia MR can affect sleep patterns?

Official product information lists a connection between this medicine and sleep. Sleep disorders, including difficulty sleeping (insomnia) and drowsiness, are documented as possible adverse reactions, though their exact frequency is currently classified as ‘Not Known’.


Q: Can people who are lactose intolerant safely take Metacardia MR?

Whether the medicine contains lactose depends on the specific tablet excipients (non-active ingredients). The tablet excipients are detailed in the official Patient Information Leaflet (PIL) or Package Leaflet, which can be reviewed to check for the presence of lactose.


Q: Is Metacardia MR effective for all stages of the condition it treats?

The medicine is indicated for a very specific condition. According to the official therapeutic indication, Metacardia MR is authorized only for the symptomatic support of patients with stable angina pectoris.


Q: Does Metacardia MR affect my driving ability?

Yes, official product information contains specific warnings regarding driving. Because adverse effects like dizziness and drowsiness have been documented, the medicine may affect your ability to drive or operate machines.


Q: What is the maximum time Metacardia MR stays active in the body?

The speed at which the medicine is eliminated from the body is measured by its half-life. According to official pharmacokinetic studies, the elimination half-life for the active substance is typically 7 to 12 hours after oral administration.


Q: Can a person who has asthma take Metacardia MR?

Official regulatory documents do not list asthma as a contraindication. Contraindications focus on pre-existing neurological conditions and severe kidney impairment. Respiratory conditions like asthma are not included in the official prohibitions for use.


Q: Does Metacardia MR have known interactions with herbal supplements like St. John's Wort?

Official regulatory documents do not explicitly list interactions with common herbal supplements. However, the product is noted to have a low potential for general pharmacokinetic interactions because it is mainly eliminated unchanged by the body.


Q: Is Metacardia MR a generic or a brand-name medicine?

Metacardia MR is a registered trade name for the medicine. The active substance is Trimetazidine dihydrochloride, which may also be available under other trade names or as a generic medicine in various markets.


Q: What is the difference between Metacardia and Metacardia MR?

The difference is based on the specific formulation of the tablet. Metacardia MR is designated as a Modified-Release (MR) formulation. This specialized form is designed to provide a slow and steady release of the active substance over an extended period.


Q: Are there specific lab tests required when taking Metacardia MR?

Routine laboratory monitoring is not typically specified in the regulatory guidelines. However, official warnings advise that signs of movement disorders (Parkinsonian symptoms) should be regularly investigated, particularly in older patients.


Q: Is Metacardia MR a medication that has withdrawal effects if stopped suddenly?

Suddenly stopping the medicine may lead to a return of the stable angina symptoms it is treating. Additionally, official warnings advise that the medication should be stopped if a movement disorder appears, as the symptoms are often reversible upon definitive withdrawal.


Q: Can Metacardia MR be taken by people with liver impairment?

Official contraindications focus on kidney function, not liver function. Severe renal impairment is a contraindication for use. Liver impairment is not listed as an explicit prohibition for use in the official regulatory documentation.


Q: Does Metacardia MR interact with the birth control pill?

Specific interactions with hormonal contraceptives are not explicitly listed in the regulatory documents. The product is generally considered to have a low potential for affecting other medicines that are metabolized by liver enzymes.


Q: Can Metacardia MR be used with other cholesterol-lowering drugs?

Specific interactions with cholesterol-lowering medicines (such as statins) are not explicitly listed. Official regulatory information indicates a low potential for pharmacokinetic interactions with medicines that are processed by the liver.


Q: Does Metacardia MR cause sexual side effects?

Sexual side effects are not listed among the documented adverse reactions of known frequency in official product information. The side effects are categorized by the frequency of occurrence (common, rare, not known).


Q: What are the most common reasons why Metacardia MR is discontinued in patients?

Official regulatory documents cite two primary scenarios for treatment withdrawal. The medicine may be discontinued by a healthcare professional if no benefit is observed after three months, or if the patient develops movement disorders, such as Parkinsonian symptoms.


Q: Does Metacardia MR have an effect on blood sugar levels?

The medicine's action is known to involve the cellular use of glucose. The drug's mechanism enhances the oxidation of glucose within heart cells. The regulatory indication section does not address the overall clinical effect on systemic blood sugar levels.


Q: Are there reports of Metacardia MR causing hair loss?

Hair loss is not listed among the documented adverse reactions of known frequency in official product information. The side effects are categorized by the frequency of occurrence (common, rare, not known).


Q: Is the Metacardia MR patient information leaflet available online?

Yes, the Patient Information Leaflet (PIL) is a publicly accessible regulatory document. National regulatory authorities (such as the MHRA or HPRA) are responsible for making this leaflet available online.

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How should Metacardia MR be stored and disposed of?

How to Store and Dispose of Metacardia MR

Official regulatory labeling dictates precise storage and handling conditions necessary to maintain the quality and stability of Metacardia MR (Trimetazidine MR tablets).

Storage Requirements

Condition Requirement
Temperature Store at a controlled room temperature (e.g., 20 to 25 C) and do not store above 30 C.
Protection Keep the tablets protected from light and moisture; store in a dry place.
Child Safety The medicine must be kept out of the sight and reach of children.

Disposal

Any unused or expired Metacardia MR and related waste material must be disposed of in accordance with local requirements. This ensures safe handling and avoids improper disposal, such as flushing the medication down drains or discarding it in household trash.

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

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