Simvastatin
From Pharmacopedia
More actions
Simvastatin
Zocor
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
No problems yet. Be the first to suggest one.
+ Add a problemTitration strategies
No titration strategies yet. Be the first to suggest one.
Effects
No effects listed yet. Be the first to suggest one.
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
Summary
Classes
Pharmacy
Starting dose
10-20 mg PO once daily in the evening (40 mg starting allowed for high CV risk)
Preparations
5, 10, 20, 40, 80 mg tablets; 4 mg/mL oral suspension
US FDA Max
40 mg/d standard; 80 mg/d restricted to patients tolerating 80 mg for ≥12 months without myopathy (post-SEARCH 2011 FDA restriction)
Pharmacology
Routes
Oral
Onset
LDL lowering at 2 weeks, max by 4 weeks
Duration
24 hours (evening dosing aligns with overnight HMG-CoA reductase peak)
Half-life
~2 hours (parent and active β-hydroxy acid metabolite); pharmacodynamic effect lasts 24 hours via target turnover[2]
Bioavailability
<5% (extensive hepatic first-pass; statin pharmacology is hepatocellular, not systemic)[2]
Pregnancy
Previously Category X; FDA removed the blanket statin contraindication in pregnancy in 2021.[citation needed]
Legal status
Rx-only in US
Purported mechanism
Simvastatin is an inactive lactone prodrug hydrolyzed to its active β-hydroxy acid, a competitive HMG-CoA reductase inhibitor.0 CYP3A4 substrate; clinically extensive drug interactions with macrolides, azoles, calcium channel blockers, and grapefruit. SLCO1B1 polymorphism (rs4149056) markedly raises plasma exposure and myopathy risk; CPIC genotype-guided dosing has the highest level of evidence for simvastatin specifically[1].
References
- ↑ CPIC Guideline for SLCO1B1, ABCG2, and CYP2C9 and Statin-Associated Musculoskeletal Symptoms, 2022. https://cpicpgx.org/guidelines/cpic-guideline-for-simvastatin-and-slco1b1/
- ↑ 2.0 2.1 FDA Prescribing Information, Zocor (simvastatin), Merck, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/019766s108lbl.pdf