Trimetazidine 2 HCl
COMPOSITION
Trimetazidine dihidrochloride 35 mg.
Excipients: q.s. for one modified release film-coated tablet.
PHARMACEUTICAL FORM
Modified release film-coated tablet.
THERAPEUTIC INDICATION
Adjunctive to established antiangina. Should not be used as monotherapy.
POSOLOGY AND METHOD Of ADMINISTRATION
One tablet at mealtimes in the morning and evening.
The benefit of the treatment should be assessed after three months and trimetazidine should be discontinued if there is no treatment response.
Due to a lack of data on efficacy and safety, children or adolescents must not use this medicinal product.
CONTRAINDICATIONS
- Hypersensitivity to trimetazidine or to any of the excipients.
- Use of this drug in nursing mothers is generally inadvisable.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
This medicinal product is generally not recommended during breastfeeding (see Pregnancy and Breast-feeding).
This medicinal product is not a curative treatment for angina attacks, nor is it indicated as an initial treatment for unstable angina, nor myocardial infarction, nor in the pre-hospital phase nor during the first days of hospitalisation.
In the event of an angina attack, the coronaropathy should be reevaluated and an adaptation of the treatment considered (medicinal treatment and possibly revascularisation).
Trimetazidine can aggravate Parkinsonian symptoms or cause Parkinsonian symptoms (tremor, akinesia, hypertonia), which should be investigated, especially in elderly patients.
The onset of falls may be related to arterial hypertension or to a postural instability (see Undesirable Effects).
In patients with renal failure, prescription of TRIZEDON® MR 35 mg is not recommended if the creatinine clearance is lower than 15 ml/min (in the absence of specific studies). In patients with severe hepatic failure, in the absence of specific studies, prescription of TRIZEDON® MR 35 mg is not recommended.
Pregnancy and Breast-feeding Pregnancy
Studies in animals have not demonstrated a teratogenic effect; however, in the absence of clinical data, the risk of malformation cannot be excluded. Therefore, for safety reasons, it is preferable to avoid prescription during pregnancy .
Breast-feeding
In the absence of data on excretion in breast milk, breastfeeding is not recommended during treatment.
Effects on ability to drive and use machines
Not applicable.
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
The clinical studies of TRIZEDON® MR 35 mg showed no evidence of interactions with other drug, particularly in elderly patients.
UNDESIRABLE EFFECTS
- Gastrointestinal disorders: gastralgia, dyspepsia, diarrhoea, constipation, nausea, vomiting.
- General disorders: asthenia.
- Nervous system disorders: headaches, vertigo, sleep disorders (insomnia, somnolence), aggravation of Parkinsonian symptoms, reversible on the discontinuation of treatment.
- Skin disorders: rash, pruritus, urticaria, angioedema or Quincke's oedema, AGEP (acute generalized exanthematous pustulosis). The onset of these effects can vary from a few hours to several days.
- Cardiovascular disorders: orthostatic hypotension, which may be associated with fainting, vertigo or a fall, especially in elderly subjects on antihypertensive treatment, palpitations, extrasystoles, tachycardia.
Overdose
Not applicable.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
OTHER CARDIOVASCULAR ANTIANGINAL DRUG
Code ATC: C01EB15
(C: cardiovascular system)
By preserving energy metabolism in cells exposed to hypoxia or ischaemia, trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and trans membrane sodium-potassium flow whilst maintaining cellular homeostasis.
In animals
Trimetazidine:
- helps maintain energy metabolism in the heart and neurosensory organs during episodes of ischaemia and hypoxia.
- reduces intracellular acidosis and alterations in trans membrane ion flow caused by ischaemia,
- decreases the migration and infiltration of poly nuclear neutrophils in ischaemic and reperfused cardiac tissue. It also reduces the size of experimental infarction's,
- exerts this action in the absence of any direct haemodynamic effect.
In man
Controlled studies in angina patients have shown that trimetazidine:
- increases coronary flow reserve, thereby delaying the onset of exercise-induced ischaemia, starting from the 15th day of treatment,
- limits rapid swings in blood pressure without any significant variations in heart rate
- significantly decreases the frequency of angina attacks,
- leads to a significant decrease in the use of trinitroglycerin.
Pharmacokinetic properties
- After oral administration, maximum concentration is found, on average, 5 hours after taking the tablet. Over 24 hours the plasma concentration remains at levels above or equal to 75% of the maximum concentration for 11 hours. Steady state is reached by the 60 hour, at the latest.
- The pharmacokinetic characteristics of TRIZEDON® MR are not influenced by meals.
- The apparent distribution volume is 4.8 l/kg; protein binding is low: in vitro measurements give value of 16%.
- Trimetazidine is eliminated primarily in the urine, mainly in the unchanged form. The elimination half-life of TRIZEDON® MR is an average of 7 hours in healthy young volunteers and 12 hours in subjects aged more than 65 years. Total clearance of trimetazidine is the result of major renal clearance which is directly correlated to creatinine clearance and, to a lesser extent, to liver clearance which is reduced with age.
- A specific clinical study carried out in an elderly population using dosage of 2 tablets per day taken in 2 doses, analysed by a kinetic population method, showed an increase in plasma exposure which does not justly a dosage alteration.
Preclinical safety data
Not applicable
STORAGE CONDITIONS
Store Below 30°C
Shelf life: 3 years
PACK SIZE
Box of 60 modified release film-coated tablets (2 blister of 30 tablets).
Reg. No: DKL1020719814Al
HARUS DENGAN RESEP DOKTER
Manufactured by :
Prafa
PRADJA PHARIN
Citeureup, Bogor - Indonesia
Under license of :
SERVIER
Les Laboratoires Servier
France
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