Lopirel Plus Tablet
Clopidogrel & Aspirin Tablet

Presentation
Lopirel Plus   tablet : Each film-coated tablet contains Clopidogrel  Bisulphate INN 97.880 mg equivalent to Clopidogrel 75 mg and Aspirin BP 75 mg.
 
Description
Lopirel Plus is a fixed-dose 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 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 released by ADP.
Aspirin is also an antiplatelet agent. Aspirin acts by causing irreversible inhibition of the cyclooxygenase enzyme, which leads to decreased formation of thromboxane A2 and ultimate inhibition of platelet aggregation.
 
Indication & Usage
Lopirel Plus is indicated for the reduction of thrombotic events as follows:
 
Recent MI, Recent Stroke or Established Peripheral Arterial Disease
For patients with a history of recent myocardial infarction (MI), recent stroke or established peripheral arterial disease, Lopirel Plus has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not) and other vascular death.
 
Acute Coronary Syndrome
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. Lopirel Plus has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia.
 
Dosage and Administration
 
Recent MI, Recent Stroke, or Established Peripheral Arterial Disease
The recommended daily dose of Lopirel Plus one tablet daily.
 
Acute Coronary Syndrome
For patients with acute coronary syndrome (unstable angina/non-Q-wave MI), Lopirel Plus should be initiated with a 4 tablet stat loading dose and then continued at one tablet daily.
 
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 hemorrhage, or bleeding disorders like
   hemophilia
 
Precautions
General: As with other anti-platelet agents, this combination drug 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 anti-platelet effect is not desired, Lopirel Plus should be discontinued 7 days prior to surgery.
GI Bleeding: The combination of Clopidogrel and Aspirin prolongs the bleeding time. So, it should be used with caution in patients who have lesions with a propensity to bleed (such as ulcers).
Thrombotic thrombocytopenic purpura (TTP): TTP has been reported rarely following use of Clopidogrel.
Reye's syndrome: Reye's syndrome may develop in individuals who have chicken pox, influenza or flu symptoms. This combination is not recommended for use in patients with chicken pox, influenza or flu symptoms.
Nasal polyps or nasal allergies: The combination drug of Clopidogrel and Aspirin should be administered with caution in patients with nasal polyps or nasal allergies.
Hepatic or Renal Impairment: This should be avoided in patients with impaired hepatic and renal function. Aspirin causes sodium and water retention in patients with renal impairment and increases the risk of gastrointestinal bleeding.

 
Side effects
The drug is generally well tolerated. Side effects that have been reported include abdominal pain, dyspepsia, gastritis, diarrhea, nausea, vomiting, constipation, gastrointestinal hemorrhage, ulceration, neutropenia, rash, palpitation, syncope, drowsiness, asthenia, neuralgia, paresthesia and vertigo.
 
Drug Interactions
Oral anticoagulants: This combination drug 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.
Hypoglycemic agents: Large doses of salicylates have hypoglycemic action and may enhance the effect of the oral hypoglycemics. Consequently, they should not be given concomitantly; if however this is necessary, the dosage of the hypoglycemic agent must be reduced while the salicylate is given.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In healthy volunteers receiving naproxen, concomitant administration of Clopidogrel was associated with increased occult gastrointestinal blood loss. This combinatoin is contraindicated in patients who are hypersensitive to NSAIDs.
Uricosuric agents: Although salicylates in larger doses are uricosuric agents, smaller amounts may decrease the uricosuric effects of probenecid, sulfinpyrazone and phenylbutazone. Aspirin may decrease the effects of probenecid, sulfinpyrazone and phenylbutazone.
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.
Alcohol: Has a synergistic effect with Aspirin in causing gastrointestinal bleeding.
Corticosteroids: Concomitant administration of Aspirin with corticosteroids may increase the risk of gastrointestinal ulceration and may reduce serum salicylate levels.
Pyrazolone derivatives (phenylbutazone, oxyphenbutazone): Concomitant administration may increase the risk of gastrointestinal ulceration.
Urinary alkalinizers: Decrease Aspirin effectiveness by increasing the risk of salicylate renal excretion.
Phenobarbital: Decreases Aspirin effectiveness by enzyme induction phenytoin, tamoxifen, tolbutamide, torasemide, fluvastatin. At high concentrations in vitro, Clopidogrel inhibits P450 (2C9). Accordingly, Clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, tolbutamide, torsemide and fluvastatin, but there are no data with which to predict the magnitude of these interactions. Caution should be used when any of these drugs is coadministered with Clopidogrel. Aspirin may also increase serum levels of phenytoin.
Propranolol: May decrease Aspirin's anti-inflammatory action by competing for the same receptors.
 
Use in Pregnancy and Lactation
Pregnancy: Adverse effects are increased in the mother and the fetus following chronic ingestion of Aspirin. Because of possible adverse effects on the neonate and the potential for increased maternal blood loss, Lopirel Plus should be avoided during the last three months of pregnancy.
 
Lactation: Lopirel Plus 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.
 
Pediatric Use
Safety and effectiveness of Lopirel Plus in the pediatric population has not been established.
 
Commercial Pack
Lopirel Plus   tablet: Each box contains 2 alu-alu strips of 10 tablets.