Sasapyrine

Uses

Sasapyrine is used for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders, pain, fever and inflammation.

How Sasapyrine works

The mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation.

Dosage

Sasapyrine dosage

Adults: The usual dosage is 3000 mg daily, given in divided doses as follows:

• Two doses of two 750 mg tablets
• Two doses of three 500 mg tablets/capsules
• Three doses of two 500 mg tablets/capsules

Some patients, e.g., the elderly, may require a lower dosage to achieve therapeutic blood concentrations and to avoid the more common side effects such as auditory.

Alleviation of symptoms is gradual, and full benefit may not be evident for 3 to 4 days, whenplasmasalicylate levels have achieved steady state. There is no evidence for development of tissue tolerance (tachyphylaxis) but salicylate therapy may induce increased activity of metabolizing liver enzymes, causing a greater rate of salicyluric acid production and excretion, with a resultant increase in dosage requirement for maintenance of therapeuticserumsalicylate levels.

Children: Dosage recommendations and indications for Sasapyrine use in children have not been established.

Should be taken with food. Take with food or milk.

Side Effects

GI symptoms, hypersensitivity reactions, skin eruptions, angioedema, weakness, rhinitis and dyspnoea, hypoprothrombinaemia. Hepatotoxicity, renal impairment, iron-deficiency anaemia, occult bleeding. Local irritation (rectally); Reye's syndrome.

Toxicity

Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome.

Precaution

Peptic ulcers; asthma, allergic disorders. Impaired hepatic or renal function. Dehydrated patients; uncontrolled hypertension. May cause acute haemolytic anaemia in patients with G6PD deficiency.

Interaction

May increase risk of liver damage when used with gold compounds. GI effects may be enhanced with alcohol or concurrent use with corticosteroids. May increase activity of coumarin anticoagulants, sulfonylureas, zafirlukast, methotrexate, phenytoin and valproate. May decrease the activity of probenecid and sulfinpyrazone.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Ingesting alcohol may increase the risk of developing a gastrointestinal bleed.
• Take with or without food. Taking salsalate with food may slow the absorption of salsalate but does not significantly impact the Cmax or AUC.

Sasapyrine Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss.

The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

Sasapyrine Drug Interaction

Moderate: aspirin, amlodipine, clopidogrel, budesonide / formoterolMinor: metoprolol, esomeprazoleUnknown: rosuvastatin, duloxetine, omega-3 polyunsaturated fatty acids, cyclobenzaprine, pregabalin, gabapentin, montelukast, levothyroxine, acetaminophen, acetaminophen / hydrocodone, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam

Sasapyrine Disease Interaction

Major: GI toxicity, renal dysfunction, Reye's syndromeModerate: anemia, coagulation, dialysis, G-6-PD deficiency, hepatotoxicity

Elimination Route

Sasapyrine is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged. The amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin). Food slows the absorption of all salicylates including salsalate.

Half Life

The parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours.

Pregnancy & Breastfeeding use

Pregnancy Category C. Sasapyrine and salicylic acid have been shown to be teratogenic and embryocidal in rats when given in doses 4 to 5 times the usual human dose. The effects were not observed at doses twice as great as the usual human dose. There are no adequate and well-controlled studies in pregnantwomen. Sasapyrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether salsalate per se is excreted in human milk; salicylic acid, the primary metabolite of Sasapyrine , has been shown to appear in human milk in concentrations approximating the maternal blood level. Thus, the infant of a mother on Sasapyrine therapy might ingest in mother†s milk 30 to 80% as much salicylate per kg body weight as the mother is taking. Accordingly, caution should be exercised when Sasapyrine is administered to a nursing woman.

Contraindication

Haemophilia, haemorrhagic disorders, gout, hypersensitivity to aspirin or NSAIDs. Children <12 yr. Pregnancy (3rd trimester) and lactation. Severe renal or hepatic impairment.

Acute Overdose

Symptoms: Tinnitus, vertigo, headache, confusion, drowsiness, sweating, hyperventilation, vomiting and diarrhea will occur. More severe intoxication will lead to disruption of electrolyte balance and blood pH, and hyperthermia and dehydration.

Treatment: Further absorption of Sasapyrine from the G.I. tract should be prevented by emesis (syrup of ipecac) and if necessary, by gastric lavage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate I.V. therapy. Adequate renal function should be maintained. Hemodialysis or peritoneal dialysis may be required in extreme cases.

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