Drug reference

Pravastatin

Statin · Antihyperlipidemic

Also known as Pravastatin sodium

StatinAntihyperlipidemic

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 12 →

AtazanavirSevereTextbook-citedKDT 7e · p948
ClarithromycinSevereTextbook-citedKDT 7e · p948
DarunavirSevereTextbook-citedKDT 7e · p948
ErythromycinSevereTextbook-citedKDT 7e · p948

Mechanism

Pravastatin is a hydrophilic HMG-CoA reductase inhibitor that, unlike the lipophilic statins (simvastatin, atorvastatin), is not metabolized by CYP3A4 but rather by sulfation and other non-CYP pathways. This eliminates the risk of drug interactions with CYP3A4 inhibitors (azole antifungals, macrolides, grapefruit juice) that can dangerously elevate levels of other statins. Its hydrophilicity limits passive diffusion into non-hepatic tissues, with hepatic uptake occurring via active organic anion transport. It produces moderate LDL reduction (30-40% at maximal dose).

Indications

Adjunct to diet for primary hypercholesterolaemia or combined (mixed) hyperlipidaemias in patients who have not responded adequately to dietary controlPrevention of cardiovascular events in patients with previous myocardial infarction or unstable anginaAdjunct to diet to prevent cardiovascular events in patients with hypercholesterolaemiaReduction of hyperlipidaemia in patients receiving immunosuppressive therapy following solid-organ transplantationHypercholesterolemiaReduction of LDL-C levelsTreat dyslipidemias, especially elevated LDL-CChildren 8 years and older (for FH)Primary hyperlipidaemias with raised LDL and total CH levels, with or without raised TG levels (Type IIa, IIb, V)Secondary hypercholesterolaemia (e.g., in diabetes, nephrotic syndrome)When reduction of LDL-CH by < 25% is contemplated

Dosing

Adult: Primary hypercholesterolaemia or combined (mixed) hyperlipidaemias: 10–40 mg daily, dose to be taken at night, dose to be adjusted at intervals of at least 4 weeks. Prevention of cardiovascular events (previous myocardial infarction or unstable angina; or hypercholesterolaemia): 40 mg daily, dose to be taken at night.…
Renal adjustment: Initial dose of 10 mg once daily in moderate to severe impairment.
Hepatic adjustment: Initial dose reduction to 10 mg daily; adjust according to response.
Max dose: 40 mg daily

Pharmacokinetics

Half-life

1 to 4 h

Bioavailability

18 ± 8%

Protein binding

50%

Metabolism

Not metabolized to any appreciable extent by the CYP system (not extensively by CYP3A4)

Excretion

Unchanged in the urine

Contraindications

Pregnancy

Side effects

Common

MyalgiaMuscle sorenessWeaknessMay be better tolerated than other statins in patients with a history of myalgias.Gastrointestinal complaintsHeadacheRashes (uncommon)Sleep disturbances (uncommon)Muscle aches (10%)

Serious

muscle effects
Myopathy
Rhabdomyolysis
Hepatotoxicity
Rise in serum transaminase
Liver damage (rare)
Myopathy (rare, < 1 per 1000)
Rhabdomyolysis (fatalities on record)

Pregnancy & lactation

Lactation

Manufacturer advises avoid—small amount of drug present in breast milk.

Drug interactions

Atazanavir

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Clarithromycin

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Darunavir

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Erythromycin

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Fluconazole

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Gemfibrozil

Severe

Textbook-cited

Increased risk of myopathy and rhabdomyolysis.

Use with caution; monitor for muscle symptoms and CK levels

Source: KDT 7e · p949

Itraconazole

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Ketoconazole

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Lopinavir

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Nicotinic Acid

Severe

Textbook-cited

Increased risk of myopathy and rhabdomyolysis

Use with caution; monitor for muscle symptoms and CK levels

Source: KDT 7e · p949

Ritonavir

Severe

Textbook-cited

Increased risk of rhabdomyolysis and myopathy.

Avoid concurrent use; if needed, use lowest statin dose

Source: KDT 7e · p948

Azole Antifungals

Severe

Textbook

Increased plasma concentrations of statins and their active metabolites, leading to an increased risk of myopathy and rhabdomyolysis.

Consider using pravastatin, fluvastatin, or rosuvastatin, as they are not extensively metabolized by CYP3A4. Carefully weigh the benefits against the risk of myopathy.

Source: G&G 14e · p736