Trimetazidine Dihydrochloride

BRAND NAMES

Common international brand names

Vastarel: This is one of the most well-known brand names and is distributed internationally.

Preductal: Another widely recognized brand name for trimetazidine.

Adexor: Available in various international markets.

Trimecor: A brand name used for trimetazidine in some countries. 

Indian brand names 

Flavedon

Cytogard

Metagard

Trivedon

Cardimax

Trimacontin

Trilong

Timzid 

MECHANISM OF ACTION

Trimetazidine works by shifting cardiac energy metabolism from fatty acid oxidation to the more oxygen-efficient glucose oxidation. It does this by inhibiting the enzyme long-chain 3-ketoacyl-CoA thiolase, which enhances ATP production during low-oxygen conditions, such as ischemia or hypoxia, allowing the heart to generate energy more efficiently with reduced oxygen demand.

PHARMACOKINETICS

Absorption

Trimetazidine is rapidly and well absorbed after oral administration. Its oral bioavailability is high, approximately 80–90%, and it reaches peak plasma concentrations (Cmax) within 1–2 hours after ingestion. Food does not significantly affect the extent of absorption, though it may slightly delay the time to peak concentration. Once absorbed, it is widely distributed in body tissues and demonstrates linear pharmacokinetics over the usual therapeutic dose range.

Distribution

The volume of distribution (Vd) of trimetazidine is approximately 1.3–1.5 L/kg. This indicates that the drug is moderately distributed throughout body tissues, with some accumulation in organs like the heart, kidneys, and liver. It is not highly protein-bound (around 16%), which contributes to its relatively wide tissue distribution.

Metabolism

Trimetazidine undergoes minimal metabolism in the body. The majority of the drug is excreted unchanged in the urine (about 95%), indicating that hepatic metabolism is limited. Only a very small fraction is metabolized in the liver via oxidation. Because of this minimal metabolism, trimetazidine has a low potential for drug–drug interactions related to liver enzymes, making it relatively safe in combination with other medications.

Excretion

Trimetazidine is mainly eliminated through the urine, with the majority excreted as the unchanged drug. More than 80% of an administered dose is removed via urine within 48 hours. Although a small portion is metabolized, the activity of these metabolites is largely unknown. The drug has an elimination half-life of approximately 6 to 7 hours, which may be prolonged in elderly patients or those with impaired kidney function.

PHARMACODYNAMICS

Trimetazidine is a metabolic anti-anginal agent that acts at the cellular level to optimize myocardial energy metabolism. Its primary mechanism is the partial inhibition of long-chain 3-ketoacyl-CoA thiolase, an enzyme involved in fatty acid β-oxidation. By doing so, it shifts cardiac energy production from fatty acid oxidation to glucose oxidation, which is more oxygen-efficient. This results in improved ATP production during ischemia or hypoxia, protecting cardiac cells from energy depletion and reducing ischemic injury. Unlike traditional anti-anginals, trimetazidine does not significantly affect heart rate, blood pressure, or coronary blood flow, making it a complementary therapy in chronic stable angina.

DOSAGE AND ADMINISTRATION

Trimetazidine is typically prescribed for the management of chronic stable angina. The standard adult dose is 20 mg three times daily for immediate-release tablets or 35 mg twice daily for modified-release formulations. It should be taken with meals to improve gastrointestinal tolerance, and modified-release tablets should be swallowed whole without crushing or chewing. Trimetazidine is usually used as an adjunct to conventional anti-anginal therapy. Dose adjustments are necessary in patients with moderate to severe renal impairment, and caution is advised in elderly patients due to the potential for drug accumulation. Therapy is generally continued long-term, based on symptom control and clinical response.

FOOD INTERACTIONS

Trimetazidine has minimal food interactions. Its absorption is not significantly affected by food, although taking it with meals may slightly delay the time to reach peak plasma concentration. This is why it is generally recommended to take the medication with meals, primarily to reduce gastrointestinal discomfort rather than due to any major interaction with food. There are no known foods that significantly alter its effectiveness or metabolism.

DRUG INTERACTIONS

Trimetazidine has a low potential for drug interactions because it undergoes minimal hepatic metabolism and is primarily excreted unchanged in the urine. It can generally be combined safely with other anti-anginal medications, such as beta-blockers, calcium channel blockers, or nitrates, to improve symptom control. It does not significantly affect blood pressure, so additive hypotensive effects with antihypertensive drugs are unlikely. Additionally, it has no major interactions with CYP450 enzymes, reducing the risk of metabolic drug interactions. However, caution is advised when using trimetazidine alongside other renally excreted drugs, especially in patients with impaired kidney function, as dose adjustments may be necessary.

CONTRAINDICATIONS

Trimetazidine is contraindicated in patients with severe renal impairment, Parkinson’s disease or other Parkinsonian symptoms, and in individuals with known hypersensitivity to the drug or its components. It is also not recommended for use in children and adolescents under 18 years of age, as its safety and efficacy have not been established in this population. Caution is advised in elderly patients and those with moderate renal impairment, with dose adjustments made as necessary.

SIDE EFFECTS

• Gastrointestinal issues.

• Neurological effects.

• Skin reactions.

• Movement disorders.

• Cardiovascular effects.

• Liver problems.

• Hypersensitivity.

• Blood disorders.

OVERDOSE

Central nervous system (CNS) effects:

• Sleepiness or drowsiness.

• Dizziness or lightheadedness.

Cardiovascular effects:

• A significant drop in blood pressure, which can lead to fainting.

• Fast or irregular heartbeats (palpitations).

Movement disorders (extrapyramidal symptoms):

• Unusual or involuntary movements, such as trembling (shaking) of the hands and fingers.

• Muscle stiffness or rigidity.

• An unsteady or shuffling gait.

• Restless legs syndrome.

TOXICITY

Trimetazidine is generally well-tolerated, but toxicity can occur, especially in elderly patients or those with renal impairment. Overdose or prolonged use may cause Parkinsonian-like symptoms (tremor, rigidity, bradykinesia), gastrointestinal disturbances, or allergic reactions. There is no specific antidote, and management is supportive, with most neurological effects reversing after discontinuation.