COMPOSITION
CombiplatTM: Each film-coated tablet contains Clopidogrel bisulfate USP equivalent to Clopidogrel 75 mg and Aspirin USP 75 mg.
PHARMACOLOGICAL INFORMATION
Pharmacological Action
Combiplat is a combination drug containing Clopidogrel and Aspirin. Clopidogrel is an inhibitor of platelet aggregation. Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP mediated activation of the GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Aspirin is also an antiplatelet agent. It acts by causing irreversible inhibition of the cyclo-oxygenase enzyme.
Mechanism of Action
Clopidogrel is a thienopyridine derivative that interferes with the platelet activation cascade. It blocks the adenosine diphosphate (ADP) receptor selectively and irreversibly & thus inhibiting the activation of the glycoprotein GPIIb/IIIA complex, the major fibrinogen receptor present in the platelet surface. Clopidogrel may antagonize the ADP induced inhibition of the adenylate cyclase possibly resulting in an elevated platelet cyclic adenosine monophosphate level after stimulation by an appropriate agonist. Aspirin is also an antiplatelet agent. It acts by causing irreversible inhibition of the cyclo-oxygenase enzyme, which leads to decreased formation of thromboxane A2. Since platelets do not synthesize new enzyme, the action of aspirin on platelet cyclo-oxygenase is permanent, lasting for the life of the platelets (7-10days).
PHARMACOKINETIC PROPERTIES
Absorption/Distribution:
The absorption of Clopidogrel is > 50% and is rapid after oral administration. Bioavailability is unaffected by food. Both the parent compound and the main metabolite bind reversibly in vitro to plasma protein (98% and 94% respectively). After oral administration, aspirin is rapidly absorbed from the stomach and proximal small intestine. The gastric mucosa is permeable to the non-ionized form of aspirin, which passes through the stomach wall by a passive diffusion process. Aspirin is distributed through outmost body fluids and tissues. Concentrations in the brain are usually low and are minimal in feces, bile and sweat.
Metabolism/Elimination:
Clopidogrel is extensively metabolized by the liver. It undergoes rapid hydrolysis into its Carboxylic acid derivative; glucoronidation also occurs. The elimination half life of the main circulating metabolite is 8 hrs with 50% excreted in the urine and 46% in the feces 5 days after dosing. Aspirin is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine and glucoronic acid and excreted largely in the urine. The plasma half-life for aspirin is approximately 15 minutes.
CLINICAL INFORMATION
Therapeutic Indications
Combiplat is indicated for the patients with a history of recent myocardial infarction (MI), recent stroke or established peripheral arterial disease.
Combiplat has been shown to reduce the rate of a combined end-point of new ischemic stroke (fatal or not), new MI (fatal or not) and other vascular death.
Combiplat is indicated for patients with acute coronary syndrome (unstable angina, non-Q-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG.
Dosage and Administration
The recommended dose is one tablet once daily.
For patients with acute coronary syndrome (unstable angina, non-Q-wave MI) Combiplat should be initiated with a 4 tablet stat loading dose and then continued at one tablet daily. Combiplat can be administered with or without food.
Use in patients with impaired renal function
Combiplat should be avoided in patients with impaired renal function. Aspirin causes sodium and water retention in patients with renal impairment and increases the risk of gastrointestinal bleeding.
Use in patients with impaired hepatic function
Use with caution in patients with severe hepatic disease.
Use in pediatric patients
Safety and efficacy in the pediatric population have not been established.
Use in Pregnancy & Lactation
Adverse effects are increased in the mother and the foetus following chronic ingestion of Aspirin. Because of possible adverse effects on the neonate and the potential for increased maternal blood loss Combiplat should be avoided during the last three months of pregnancy. It is not recommended for use during breast feeding because of the possible risk of developing Reye's syndrome.
Side Effects
The drug is generally well tolerated. Side-effects that have been reported include abdominal pain, dyspepsia, gastritis, diarrhoea, nausea, vomiting, constipation, gastrointestinal hemorrhage, ulceration, palpitation, drowsiness and vertigo.
Contraindications
Hypersensitivity to Clopidogrel or Aspirin and/or NSAIDs.
Active pathological bleeding such as peptic ulcer or intracranial hemorrhage or bleeding disorders like hemophilia.
Recent history of gastrointestinal bleeding.
Drug interactions
Use caution with phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin, and non-steroidal anti-inflammatory agents.
Over dosage
Overdose following Clopidogrel administration may lead to prolonged bleeding time and subsequent bleeding complications.
A single oral dose of Clopidogrel at 1500 or 2000 mg/kg was lethal to mice and to rats and at 3000 mg/kg to baboons. Symptoms of acute toxicity were vomiting (in baboons), prostration, difficult breathing, and gastrointestinal hemorrhage in all species.
Aspirin overdose has serious consequences and is potentially lethal. Possible effects of overdose include tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma and death. Overdose can be acute or chronic; that is, a person can overdose by taking one very large dose or smaller doses over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal with a mortality rate of 25%. The most common cause of death during an aspirin overdose is noncardiogenic pulmonary edema.
An acute-overdose patient must be taken to a hospital immediately.
PHARMACEUTICAL INFORMATION
Storage Conditions
Store in a cool and dry place away from light. Keep out of reach of children.
Presentation & Packaging
CombiplatTM: Each commercial box contains 30 tablets in Alu-Alu blister pack. |