simvastatin and acetylsalicylic acid

C10BX01

Forms & Strengths

Simvastatin / Acetylsalicylic acid (Aspirin) fixed-dose combination capsules: 20 mg / 81 mg
Simvastatin / Acetylsalicylic acid (Aspirin) fixed-dose combination capsules: 40 mg / 81 mg
Simvastatin / Acetylsalicylic acid (Aspirin) fixed-dose combination capsules: 20 mg / 325 mg
Simvastatin / Acetylsalicylic acid (Aspirin) fixed-dose combination capsules: 40 mg / 325 mg

Adult Dosing

Primary or secondary prevention of cardiovascular events: One capsule daily in the evening, tailored to individual component requirements (simvastatin 20-40 mg and aspirin 81-325 mg)
Maximum recommended simvastatin dose is 40 mg daily due to increased risk of myopathy at 80 mg

Pediatric Dosing

Safety and efficacy in pediatric patients have not been established; combination use is not recommended in children

Indications

Reduction of cardiovascular morbidity and mortality in patients with established coronary heart disease or high risk for coronary events
Adjunct to diet to reduce elevated total-C, LDL-C, apoB, and triglycerides, and to increase HDL-C while providing antiplatelet therapy

Mechanism of Action

Simvastatin: Competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis
Acetylsalicylic acid (Aspirin): Irreversible inhibition of platelet cyclooxygenase-1 (COX-1), blocking thromboxane A2 synthesis and inhibiting platelet aggregation

Contraindications

Hypersensitivity to simvastatin, aspirin, other salicylates, or any component of the formulation
Active liver disease or unexplained persistent elevations of serum transaminases
Pregnancy and lactation
Patients with asthma, rhinitis, and nasal polyps (aspirin-triad) at risk for severe hypersensitivity reactions
Children and teenagers with viral infections (risk of Reye's syndrome from aspirin component)
Active pathological bleeding such as peptic ulcer or intracranial hemorrhage
Concomitant use of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin, HIV protease inhibitors)

Adverse Reactions

Simvastatin-related: Myalgia, myopathy, rhabdomyolysis, elevations in serum transaminases, headache, constipation, nausea
Aspirin-related: Dyspepsia, gastrointestinal ulceration, upper GI bleeding, bruising, prolonged bleeding time, hypersensitivity reactions, bronchospasm

Drug Interactions

Strong CYP3A4 inhibitors (e.g., cyclosporine, danazol, gemfibrozil, tipranavir/ritonavir) significantly increase simvastatin plasma levels and myopathy risk
Coumarin anticoagulants (e.g., warfarin): Aspirin increases bleeding risk and may displace or be displaced; monitor INR closely
NSAIDs (e.g., ibuprofen): May attenuate the irreversible antiplatelet effect of low-dose aspirin and increase GI ulceration risk
ACE inhibitors and ARBs: Aspirin may decrease the antihypertensive effect
Amiodarone, amlodipine, ranolazine: Limit simvastatin dose to 20 mg daily due to increased myopathy risk

Curated Content: Needs Vetting Before Put to Clinical Use