Tromalyt 150 mg

Tromalyt 150 mg is indicated to:

1. Reduce the risk of death and myocardial infarction (MI) in patients with chronic coronary artery disease, such as patients with a history of MI or unstable angina pectoris or with chronic stable angina
2. Reduce the risk of death and recurrent stroke in patients who have had an ischemic stroke or transient ischemic attack

Limitation of Use

Use immediate-release aspirin, not Tromalyt 150 mg in situations where a rapid onset of action is required (such as acute treatment of myocardial infarction or before percutaneous coronary intervention).

The recommended dose of Tromalyt 150 mg is one capsule (162.5 mg) once daily. Take the capsules with a full glass of water at the same time each day.

Swallow Tromalyt 150 mg capsules whole. Do not cut, crush or chew capsules.

Do not take Tromalyt 150 mg 2 hours before or 1 hour after consuming alcohol.

Tromalyt 150 mg is contraindicated:

• In patients with a hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs).
• In patients with the syndrome of asthma, rhinitis, and nasal polyps. Tromalyt 150 mg may cause severe urticaria, angioedema, or bronchospasm.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Risk Of Bleeding

Tromalyt 150 mg increases the risk of bleeding. Risk factors for bleeding include the use of other drugs that increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents, and chronic use of NSAIDs).

Peptic Ulcer Disease

Tromalyt 150 mg may cause gastric ulceration and bleeding. Avoid Tromalyt 150 mg in patients with active peptic ulcer disease.

Fetal Toxicity

Tromalyt 150 mg can cause fetal harm when administered to a pregnant woman. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence for intracranial hemorrhage in premature infants, stillbirths and neonatal death. Because NSAIDs may cause premature closure of the fetal ductus arteriosus, avoid Tromalyt 150 mg in the third trimester of pregnancy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No carcinogenesis, mutagenesis or impairment of fertility studies were conducted with Tromalyt 150 mg. Aspirin is not considered to be genotoxic or carcinogenic. Studies with oral aspirin in pregnant rats demonstrated the occurrence of fetal malformations at oral doses at or above 250 mg/kg [Human equivalent dose (HED) 40 mg/kg].

Use In Specific Populations

Pregnancy

Avoid use during the third trimester of pregnancy because NSAIDs such as Tromalyt 150 mg may cause premature closure of the fetal ductus arteriosus. Salicylate products have also been associated with alterations in maternal and neonatal hemostasis mechanisms, decreased birth weight, and with perinatal mortality.

Labor And Delivery

Avoid Tromalyt 150 mg 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

Because of the potential for serious adverse reactions in nursing infants from Tromalyt 150 mg, choose either to discontinue Tromalyt 150 mg or discontinue nursing.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In a large collaborative overview of aspirin for vascular event prevention, including over 14000 patients over 65 years of age, no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Hepatic Impairment

Avoid Tromalyt 150 mg in patients with severe hepatic insufficiency.

Renal Impairment

Avoid Tromalyt 150 mg in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute).

Clinical Trials Experience

The following is a list of adverse reactions that have been reported in the literature for products containing low dose aspirin.

Central Nervous System: Agitation, cerebral edema, coma, confusion, dizziness, headache, lethargy, seizures.

Fluid and Electrolyte: Hyperkalemia, metabolic acidosis, respiratory alkalosis.

Gastrointestinal: Dyspepsia, hepatic enzyme elevation, hepatitis, Reye's Syndrome

Renal: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure.

Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. The early signs of salicylic overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approaching 200 mcg/mL. Plasma concentrations of aspirin above 300 mcg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 mcg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g. For real or suspected overdose, contact a Poison Control Center immediately.

Signs and Symptoms

In acute overdose, severe acid-base and electrolyte disturbances may occur and are complicated by hyperthermia 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 or lavage is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage or emesis, administer activated charcoal, as a slurry, if less than 3 hours have passed since ingestion.

Severity of aspirin intoxication is determined by measuring the blood salicylate level. Monitor acid-base status with serial blood gas and serum pH measurements. Maintain fluid and electrolyte balance.

In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Replace fluid intravenously and correct acidosis. Monitor plasma electrolytes and pH to promote alkaline diuresis of salicylate if renal function is normal. Glucose may be required to control hypoglycemia.

Hemodialysis and peritoneal dialysis can reduce the body aspirin content. 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.

The dose-response relationship for Tromalyt 150 mg and immediate release (IR) aspirin towards COX-1 inhibition was characterized by examining the inhibition of serum TXB2 and urine 11dehydro-TXB2 at 24 h following a single dose. Doses over the range of 20 mg to 325 mg for Tromalyt 150 mg and 5 mg to 81 mg for IR aspirin respectively were studied. Half-maximal inhibition of serum TXB2 and urine 11-dehydro-TXB2 occurred with doses of Tromalyt 150 mg (ID50) about 2-fold the dose of immediate release (IR) aspirin. Based on this relationship, the pharmacodynamic effect of Tromalyt 150 mg 162.5 mg is similar to that attained with IR aspirin 81 mg. The mean inhibition of serum TXB2 following Tromalyt 150 mg (82%) is lower when compared to IR aspirin 81 mg (93%) following the first dose. However, upon repeat administration, near maximal inhibition of serum TXB2 is achieved, similar to what is achieved following repeated daily doses of IR aspirin.

Following oral administration, Tromalyt 150 mg exhibits extended release of aspirin from the encapsulated microparticles, thereby prolonging the absorption of aspirin across the GI tract compared to IR aspirin (Figure 1). Once absorbed, aspirin is metabolized, distributed, and excreted in a manner similar to that of aspirin absorbed from IR dosage forms.

Figure 1: Mean acetylsalicylic acid concentration-time profile following single dose administration of 162.5 mg Tromalyt 150 mg or 81 mg immediate release ASA

Absorption

Following administration of Tromalyt 150 mg, the time to reach peak plasma concentration of aspirin is slightly longer compared to following IR aspirin dosage form. Median Tmax for Tromalyt 150 mg is about 2 h when compared to 1 h following IR aspirin (see Figure 1). The mean Cmax for Tromalyt 150 mg is approximately 35% of that following IR aspirin 81 mg. The area under the plasma concentration-time curve for aspirin following administration of Tromalyt 150 mg is approximately 70% of that following IR aspirin. The rate of Tromalyt 150 mg absorption is dependent on food, alcohol, and gastric pH.

Distribution

The volume of distribution of usual doses of aspirin in normal subjects averages approximately 170 mL/kg of body weight.

Metabolism

Aspirin is rapidly hydrolyzed in the plasma to salicylic acid such that plasma levels of aspirin following Tromalyt 150 mg administration are essentially undetectable 4-8 hours after dosing. In contrast to immediate release aspirin, measurable levels of salicyclic acid at 24 hours following a single dose of Tromalyt 150 mg were observed. Salicylic acid is primarily conjugated in the liver to form salicyluric acid, a phenolic glucuronide, an acyl glucuronide, and a number of minor metabolites.

Elimination

The mean plasma half-life of aspirin may range from 20 to 60 min. Following therapeutic doses, approximately 10% is found excreted in the urine as salicylic acid, 75% as salicylic acid, and 10% phenolic and 5% acyl glucuronides of salicylic acid.