SAP

Therapeutic Group: Cardio-Vascular Drugs Chemical Composition: ASPIRIN License by : Unipharma Dosage form: Extended release tablets
Information about SAP

COMPOSITION:

Each film coated extended release tablet contains:81 mg acetylsalicylic acid.

 Excipients:

Core excipients: Microcrystalline cellulose, Lactose anhydrous,hypromellose, Aerosile, stearic acid.

Film coating excipients: Opaglos regular.

Mechanism of Action:

 Aspirin is a more potentinhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. The differences in activity between aspirin and salicylic acid are thought to be due to the acetyl group on the aspirin molecule, which is responsible for the inactivation of cyclo-oxygenasevia acetylation.

Aspirin affects platelet aggregation by irreversibly inhibiting prostaglandin cyclo-oxygenase.This effect lasts for the life of the platelet and prevents the formation ofthe platelet aggregating factor. At somewhat higher doses, aspirinreversibly-inhibits the formation of prostaglandin I2 (prostacyclin), which is an arterial vasodilator and inhibits platelet aggregation. At higher dosesaspirin is an effective anti-inflammatory agent, partially due to inhibition of inflammatory mediators via cyclooxygenase inhibition in peripheral tissues.

Pharmacokinetics:

Absorption: in general immediate release aspirin is will and completely absorbed from the gastrointestinal (GI) tract, following absorption aspirin is hydrolyzed tosalicylic acid with peak plasma levels occurring within 1-2 hours of dosing.

Distribution: Salicylicacid is widely distributed to all tissues and fluids in the body including the central nervous system (CNS), breast milk, and fetal tissue. The protein binding of salicylate is concentration-dependent. At low concentrations approximately 90 % of plasma salicylate is bound to albumin while at higher concentrations only about 75 % is bound.

Metabolism: After hydrolization Salicylic acid is primarily conjugated in the liver. Salicylicacid has a plasma half-life of approximately 6 hours.

 Elimination: Renal excretion of unchanged drug depends upon urine pH. Alkalinization of the urine is a key concept in the management of salicylate overdose. Following therapeutic doses,approximately 10% is found excreted in the urine as salicylic acid, 75% assalicyluric acid.

INDICATIONS:

1.       Vascular Indications: Aspirin is indicated to:

Reduce the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli

Reduce the risk of vascular mortality in patients with a suspected acute MI

Reduce the combined risk of death and nonfatal Mlin patients with a previous MI or unstable angina pectoris. .

Reduce the combined risk of MI and sudden death inpatients with chronic stable angina pectoris.

2.Revascularization Procedures: Aspirin is indicated inpatients who have undergone revascularization procedure (Coronary artery by pass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA) orcarotid endarterectomy) when there is a preexisting condition for which aspirinis already indicated.

3.Rheumatologic disease indication: aspirin is indicated for the relief of the signs and symptoms of rheumatoid arthritis, juvenile rheumatoidarthritis, osteoarthritis, spondyloarthropathies, and arthritis and pleurisy associated with Systemic lupus erythematous.

CONTRAINDICATIONS:

-In patients with known allergy to non-steroidalanti- inflammatory drug and in patients with the syndrome of asthma, rhinitis,and nasal polyps. Aspirin may cause severe urticaria, angioedema, orbronchospasm (asthma).

-Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye'ssyndrome with concomitant use of aspirin in certain viral illnesses.

ADVERSER ACTIONS:

Body as a WholeFever, hypothermia, thirst.

Cardiovascular: Dysrhythmias,hypotension, tachycardia.

Central NervousSystem: Agitation, cerebral edema, coma, confusion, dizziness headache, subdural orintracranial hemorrhage, lethargy, seizures.

Fluid and Electrolyte:Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis

Gastrointestinal: Dyspepsia, GIbleeding, ulceration and perforation, nausea, vomiting, transient elevations of hepatic enzymes, hepatitis, Reye's syndrome, pancreatitis.

Hematologic: Prolongation of the prothrombin time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia.

Hypersensitivity: Acuteanaphylaxis, angioedema, asthma; bronchospasm, laryngeal edema, urticaria

Musculoskeletal:Rhabdomyolysis.

Metabolism: Hypoglycemia(in children), hyperglycemia.                                            

Reproductive: Prolongedpregnancy and labor, stillbirths, lower birth weight infants, antepartum andpostpartum bleeding.

Respiratory: hyperpnea,pulmonary edema, tachypnea.

Senses: hearing loss,tinnitus.

Urogenital: interstitialnephritis, papillary necrosis, proteinuria, renal insufficiency and failure.

Warnings and PRECAUTIONS:

Coagulation abnormalities:Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect patients with inherited(hemophilia) or acquired (liver disease or vitamin K deficiency) bleeding disorders.

GI Side Effects: GIside effects include stomach pain, heartburn, nausea, vomiting, and gross GIbleeding. Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms

Peptic Ulcer Disease: Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding.

Renal Failure: Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10mL/minute).

Hepatic Insufficiency: Avoid aspirin in patients with severe hepatic insufficiency.        

Sodium Restricted Diets:Patients with sodium-retaining states, such as congestive heart failure or renal failure, should avoid sodium-containing buffered aspirin preparations because of their high sodium content.

Laboratory Tests: Aspirin has been associated with elevated hepatic enzymes, blood urea nitrogenand serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time.

Alcohol: patients who consume three or more alcoholic drinks every day should be counseled about the bleeding risks involved with chronic Heavy alcohol use while taking aspirin

 DRUG INTERACTIONS:

Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the renin-angiotensin conversion pathway.

 Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at renal tubule for secretion.

Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation the rapy are at increased risk for bleeding because of drug interactions and the effect on platelets. Aspirin can displace wayfaring from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk.

Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels.

Beta Blockers: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention.

Diuretics: The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention.

Methotrexate: Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in the elderly or renal impaired.                                 

NSAIDs: The concurrent use of aspirin with other NSAID's should be avoided because this may increase bleeding or lead to decreased renal function.

Oral Hypoglycemics Moderate doses of aspirin may increase the effectiveness of oral hypoglycemicdrugs, leading to hypoglycemia.

Uricosuric Agents (Probenecid and Sulfinpyrazone): Salicylates antagonize the uricosuricaction of uricosuric agents.

PREGNANCY& LACTATION:

 Pregnancy: Pregnant women should take aspirin only if clearly needed. Because of the known effects of NSAIDs on the fetal cardiovascular system, use during the third trimester of pregnancy should be avoided

Labor &Delivery: Aspirin should be avoided 1 week prior to and during labor and delivery because it can result in excessive blood loss at delivery. Prolonged gestation and prolonged labor due to prostaglandin inhibition have been reported.

Nursing Mothers :Nursing mothers should avoid using aspirin because salicylate is excreted in breast milk. Use of high doses may lead to rashes, platelet abnormalities and  bleeding in nursing infants.

DOSAGE and ADMINISTRATION:

Ischemic Stroke and TIA:50-325 mg once a day, continue therapy indefinitely.                           

Suspected Acute Myocardial infarction (MI): The initial dose of 160-162.5 mg is administered as soon as an Ml is suspected. The maintenance dose of 160-162.5 mg a day is continued for 30 days post-infarction, after 30 days consider further the rapy  based on dosage for prevention of recurrent MI.

Prevention of recurrent MI: 75-325 mg once a day, continue therapy indefinitely.      

Unstable angina pectoris: 75-325 mg on cea day, continue therapy indefinitely.            

Chronic Stable Angina Pectoris: 75-325mg once a day, continue therapy indefinitely.

Coronary artery bypass grafting (CAEG): 325 mg daily starting 6 hours  post-procedure. Continue therapy for one year post-procedure.

Percutaneoustrans-luminal coronary angioplasty (PTCA): The initial dose of 325 mg should be given 2 hours pre-surgery. Maintenance dose is 160-325mg daily, continue therapy indefinitely.

CarotidEndarterectomy: Doses of 80 mg once daily to 650 mg twice daily, started pre-surgery, are recommended, continue therapy indefinitely.

Rheumatoid arthritis: The initial dose is 3 g a day in divided doses. Increase as needed for anti-inflammatory efficacy with target plasma salicylates level of 150-300 mcg/ml. at high doses(plasma levels of greater than 200 mcg/ml), the incidence of toxicity increase.

Juvenile rheumatoid arthritis: Initial doseis 90-130 mg/kg/day in divided doses, Increase as needed for anti-inflammatory efficacy with target plasma salicylates levels of 150-300 mcg/ml.

Spondyloarthropathies: Up to (4g) dayin divided doses

Osteoarthritis: Up to (3g) per day individed doses

Arthritis and pleurisy of SLE: The initialdose is (3g) a day in divided doses. Increase as needed for anti-inflammatory efficacy with target plasma salicylate level of 150-300 mcg/ml .

OVER DOSAGE:

Signs and Symptoms: The early signs of salicylate overdose including tinnitus occur at plasma concentration approaching 200 mcg/ml. plasma concentrations of aspirin above 300mcg/ml is clearly toxic. In acute overdose, severe acid-base and electrolyte disturbances may occur and are complicated by hypothermia and dehydration.Respiratory alkalosis occurs early while hyperventilation is present, but is quickly followed by metabolic acidosis.

Treatment: Treatment  consists primarily of supporting vital functions, increasing salicylate elimination,and correcting the acid-base disturbance. Gastric emptying and/or lavage are recommended as soon as possible after ingestion, even if the patient hasvomited spontaneously. After that administration of activated charcoal, is beneficial, if less than 3 hours have passed since ingestion, it should not be employed prior to emesis and lavage. Hemodialysis and peritoneal dialysis can be performed to reduce the body drug content.

STORAGE conditions:

Store at 250 in dry place.

Package:

Carton pack contains 20 or 40 extended release film coated tablets.