AS-CLOP 75
-
Chemical Name:
Clopidogrel - Aspirin -
Therapeutic Category:
Cardiovascular drugs -
Pharmacologic Category:
Tow Antiplatelet Agents: Thienopyridine - Salicylate -
Pharmaceutical Form:
Tablets -
Composition:
Clopidogrel 75mg - Aspirin 75mg
ASCLOP
Film Coated Tablets
Clopidogrel (Bisulfate) & Aspirin
1.COMPOSITION:
- ASCLOP 75/75 –F.C. Tablets: Each F.C tablet contains 75 mg of Clopidogrel (as Bisulfate), and 75 mg of Aspirin.
- ASCLOP 150/75 –F.C. Tablets: Each F.C tablet contains 75 mg of Clopidogrel (as Bisulfate), and
150 mg of Aspirin.
2.PHARMACOLOGY:
ASCLOP is a fixed-dose combination containing clopidogrel and aspirin.
Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP.
Aspirin is also an antiplatelet agent, which acts by causing irreversible inhibition of the cyclooxygenase enzyme. This leads to decreased formation of thromboxane A2.
Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg with peak plasma levels of the main circulating metabolite occurring approximately 1 hour after dosing.
Clopidogrel is a prodrug. The active metabolite, a thiol derivative, is formed by oxidation of clopidogrel.
Clopidogrel and the main circulating metabolite bind reversibly to human plasma proteins (98% and 94%, respectively). Clopidogrel is extensively metabolised by the liver.
Following an oral dose clopidogrel approximately 50% was excreted in the urine and approximately 46% in the feces in the 120 hour interval after dosing, and the elimination half-life of the main circulating metabolite was 8 hours.
Aspirin undergoes moderate hydrolysis to salicylic acid in the liver and the gastrointestinal wall, so 50-75% of an administered dose reaching the systemic circulation as intact aspirin.
Aspirin is poorly bound to plasma proteins and its apparent volume of distribution is low. Its metabolite, salicylic acid, is highly bound to plasma proteins, but its binding is concentration-depended.
Aspirin is rapidly hydrolyzed in plasma to salicylic acid with a half-life of 20minutes that after 2-2.5 hours of the dose aspirin levels are essentially undetectable. The elimination half-life of acetylsalicylic acid is 0.33 hours and of salicylic acid is 1.71 hours.
3.INDICATIONS:
ASCLOP is indicated for the prevention of ischemic events, myocardial infarction, stroke and cardiovascular death in patients with acute coronary syndrome.
4.DOSAGE & ADMINISTRATION:
Prevention of ischemic events: The recommended dose is one F.C tablet once daily.
Acute coronary syndrome:
Loading dose: Four F.C tablets.
Maintenance: One F.C tablet daily.
5.CONTRAINDICATIONS:
- Hypersensitivity to Clopidogrel.
- Hypersensitivity to Aspirin and/or non-steroidal anti-inflammatory agents.
- Recent history of gastrointestinal bleeding.
- Active pathological bleeding such as peptic ulcer or intracranial haemorrhage, or bleeding disorders like haemophilia.
6.DRUG INTERACTIONS:
- ASCLOP should be used with caution when anticoagulants are prescribed concurrently, since both aspirin and clopidogrel may depress the concentration of prothrombin in plasma and thereby increase bleeding time.
- Large doses of salicylates have hypoglycemic action and may enhance the effect of the oral hypoglycemics. Therefore it should be used with caution concomitantly. If however this is necessary, the dosage of the hypoglycemic agent must be reduced while the salicylate is given.
- NSAIDs and clopidogrel should be coadministered with caution because that was associated with increased occult gastrointestinal blood loss.
- Aspirin in small amounts may decrease the uricosuric effects of probenecid, sulfinpyrazone and phenylbutazone.
- Alcohol has a synergistic effect with aspirin in causing gastrointestinal bleeding.
- Concomitant administration of aspirin with corticosteroids or Pyrazolone derivatives may increase the risk of gastrointestinal ulceration and may reduce serum salicylate levels.
- Urinary alkalinizers decrease aspirin effectiveness by increasing salicylate renal excretion.
- Clopidogrel at high concentrations inhibits P450 (2C9). Accordingly, clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, tolbutamide, torsemide and fluvastatin, therefore caution should be used when any of these drugs is coadministered with clopidogrel.
- Propranolol may decrease aspirin's anti-inflammatory action by competing for the same receptors.
- Spironolactone: Sodium excretion produced by spironolactone may be decreased in the presence of salicylates. Salicylates can produce changes in thyroid function tests. Salicylates should be used with caution in patients with severe hepatic damage, pre-existing hypoprothrombinemia or vitamin K deficiency and in those undergoing surgery.
7.WARNINGS & PRECAUTIONS:
- Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions. If a patient is to undergo elective surgery and an antiplatelet effect is not desired, clopidogrel should be discontinued 7 days prior to surgery.
- Thrombotic thrombocytopenic purpura (TTP) has been reported rarely following use of clopidogrel which is a serious condition requiring prompt treatment, and characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological findings, renal dysfunction, and fever.
- Reye's syndrome may develop in individuals who have chicken pox, influenza or flu symptoms so ASCLOP is not recommended for use in these cases.
- ASCLOP prolongs the bleeding time. ASCLOP should be used with caution in patients who have lesions with a propensity to bleed such as ulcers.
- ASCLOP should be administered with caution to patients with nasal polyps or nasal allergies.
- ASCLOP should be avoided in patients with impaired hepatic function or with impaired renal function. The aspirin causes sodium and water retention in patients with renal impairment and increased the risk of GI bleeding.
8.USE IN PREGNANCY & LACTATION:
ASCLOP should be avoided during the last three months of pregnancy due to possible adverse effects on the neonate and the potential for increased maternal blood loss.
ASCLOP should be avoided in nursing mothers because of the possible risk of developing Reye's syndrome. Regular use of high doses of aspirin could impair platelet function and produce hypoprothrombinemia in infants if neonatal vitamin K levels are low.
9.PEDIATRIC USE:
Safety and effectiveness this drug in the pediatric population have not been established.
10.UNDESIRABLE EFFECTS
The drug is generally well tolerated. Side effects that have been reported include abdominal pain, dyspepsia, gastritis, diarrhea, nausea, vomiting, constipation, gastrointestinal haemorrhage, ulceration, neutropenia, rash, palpitation, syncope, drowsiness, asthenia, neuralgia, paresthesia and vertigo.
11.OVERDOSAGE:
- Clopidogrel: Overdose following clopidogrel administration may lead to prolonged bleeding time and subsequent bleeding complications. Symptoms of acute toxicity were vomiting, prostration, difficult breathing, and gastrointestinal hemorrhage in all species. The treatment of clopidogrel toxicity is based on biological plausibility, platelet transfusion may be appropriate if quick reversed is required.
- Aspirin: The early signs of salicylic overdose including tinnitus. In severe cases, hyperthermia and hypovolemia may occur. Replacement fluid should be administered intravenously and augmented with correction of acidosis. Plasma electrolytes and pH should be monitored to promote alkaline diuresis of salicylate if renal function is normal. Infusion of glucose may be required to control hypoglycemia.
Hemodialysis and peritoneal dialysis can be performed to reduce the body drug content specially in patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required. Exchange transfusion may be indicated in infants and young children.
12.PACKAGING:
- ASCLOP 75/75 – F.C. Tablets: A pack of 10 or 30 film coated tablets
- ASCLOP 150/75 – F.C. Tablets: A pack of 10 or 30 film coated tablets.
13.STORAGE:
Store at temperature below 25°C away from moisture.
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