Dosing and uses of Pravachol (pravastatin)
Adult dosage forms and strengths
tablets
- 10mg (generic only)
- 20mg
- 40mg
- 80mg
Hyperlipidemia, Primary Prevention of Coronary Events, Secondary Prevention of Cardiovascular Events
May be beneficial for prophylaxis of cardiovascular events in at-risk patients, even if patients have normal levels of cholesterol.
10-40 mg PO qDay; not to exceed 80 mg/day
Initiate with 10 mg qHS if taking immunosuppressants like cyclosporine concurrently; not to exceed 20 mg/day
Limit maximum to 40 mg/day if taking concurrently with clarithromycin
Dose adjustments should be made at intervals of 4 weeks or more; individualize dosing according to baseline LDL cholesterol levels
Dosing Considerations
Overdose management
- Adverse drug reactions from overdose may include peripheral neuropathy, diarrhea, increased K+, myopathy, rhabdomyolysis, acute renal failure, elevated LFTs, eye lens opacities
- Treatment is supportive
Dosing Modifications
Renal impairment
- 10 mg PO qDay initially
Hepatic impairment
- Contraindicated if active liver disease or unexplained persistent elevations of serum transaminases
Pediatric dosage forms and strengths
tablets
- 10mg (generic only)
- 20mg
- 40mg
- 80mg
Heterozygous Familial Hypercholesterolemia
8-13 years: 20 mg PO qDay
14-18 years: 40 mg PO qDay
Coadministration with cyclosporine: Initiate with 10 mg qHS; not to exceed 20 mg/day
Limit maximum to 40 mg/day if taking concurrently with clarithromycin
Dose adjustments should be made at intervals of 4 weeks or more; individualize dosing according to baseline LDL cholesterol levels
Pravachol (pravastatin) adverse (side) effects
1-10%
Nausea/vomiting (7%)
Diarrhea (6%)
Headache (2-6%)
Chest pain (4%)
Fatigue (4%)
Rash (4%)
Cough (3%)
Heartburn (3%)
Flulike symptoms (2%)
Myalgia (2%)
Frequency not defined
Myopathy
Rhabdomyolysis
Warnings
Contraindications
Hypersensitivity
Active liver disease, elevated LFTs
Pregnancy, lactation
Cautions
Nonserious and reversible cognitive side effects may occur
Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake
Risk of rhabdomyolysis; predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment; discontinue if myopathy develops
Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persists despite discontinuation of statin
Max response 4-6 weeks
Recent liver disease, symptoms of liver disease
Heavy alcohol use
Use caution with other drugs that increase risk of myopathy (eg, fibrates)
Rule out secondary causes of hyperlipedemia before initiating therapy
Monitor liver function periodically
Postmarketing Reports
Musculoskeletal: Polymyositis
Respiratory: Interstitial lung disease
Psychiatric: Nightmare
Pregnancy and lactation
Pregnancy: Administer to women of childbearing age only when patients are highly unlikely to conceive and have been informed of potential hazards; if the patient becomes pregnant while taking this class of drug, discontinue therapy immediately and apprise patient of potential hazard to fetus
Lactation: Enters breast milk; contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Pravachol (pravastatin)
Mechanism of action
HMG-CoA reductase inhibitor; inhibits the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase
Absorption
Bioavailability: 17%
Onset: 2 weeks
Peak effect: 4 weeks
Peak serum time: 1-1.5 hr
Distribution
Protein bound: 43-55%
Vd: 0.46 L/kg
Metabolism
Undergoes extensive first-pass extraction by liver
Metabolites: 3-alpha-hydroxy isomer and 3-alpha, 5-beta, 6-beta trihydroxy metabolite (inactive)
Elimination
Half-life: 2.6-3.2 hr
Excretion: Feces (71%); urine (<20%)
Pharmacogenomics
SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes
This polymorphism is proposed to reduce transport into the liver, the main site of statin metabolism and elimination, resulting in elevated plasma concentrations
SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin), compared with more those that are more lipophilic (eg, atorvastatin, pravastatin, simvastatin)
Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism
SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)
Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and 16.9-fold higher in CC homozygotes compared with TT homozygotes
Genetic testing laboratories
- Optivia Biotechnology, Inc (https://optiviabio.com)
