Chemical formula: C₂₃H₃₆O₇ Molecular mass: 424.528 g/mol PubChem compound: 54687
Pravastatin interacts in the following cases:
A starting dose of 10 mg a day is recommended in patients with moderate or severe renal impairment or significant hepatic impairment. The dosage should be adjusted according to the response of lipid parameters and under medical supervision.
Vitamin K antagonists: As with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of pravastatin in patients treated concomitantly with vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant) may result in an increase in International Normalised Ratio (INR). Discontinuation or down-titration of Pravastatin may result in a decrease in INR. In such situations, appropriate monitoring of INR is needed.
Warfarin and other oral anticoagulants: Bioavailability parameters at steady state for pravastatin were not altered following administration with warfarin. Chronic dosing of the two products did not produce any changes in the anticoagulant action of warfarin.
he use of fibrates alone is occasionally associated with myopathy. An increased risk of muscle related adverse events, including rhabdomyolysis, have been reported when fibrates are co-administered with other statins. These adverse events with pravastatin cannot be excluded, therefore the combined use of pravastatin and fibrates (e.g. gemfibrozil, fenofibrate) should generally be avoided. If this combination is considered necessary, careful clinical and CK monitoring of patients on such regimen is required.
oncomitant administration resulted in approximately 40 to 50% decrease in the bioavailability of pravastatin. There was no clinically significant decrease in bioavailability or therapeutic effect when pravastatin was administered one hour before or four hours after colestyramine or one hour before colestipol.
Concomitant administration of pravastatin and ciclosporin leads to an approximately 4-fold increase in pravastatin systemic exposure. In some patients, however, the increase in pravastatin exposure may be larger. Clinical and biochemical monitoring of patients receiving this combination is recommended.
Due to the increased risk of myopathy/rhabdomyolysis, clinical and biological monitoring is recommended, especially at the start of the combination of pravastatin with colchicine.
In one of the two interaction studies with pravastatin and erythromycin a statistically significant increase in pravastatin AUC (70%) and Cmax (121%) was observed. In a similar study with clarithromycin a statistically significant increase in AUC (110%) and Cmax (127%) was observed. Although these changes were minor, caution should be exercised when associating pravastatin with erythromycin or clarithromycin.
There is an increased risk of rhabdomyolysis when statins are combined with lenalidomide. Enhanced clinical and biological monitoring is warranted, especially in the first weeks of treatment.
In an interaction study where pravastatin was administered in combination with rifampicin, a nearly 3-fold increase in the AUC and Cmax of pravastatin was observed. Therefore, caution should be exercised when combining pravastatin with rifampicin, although both are given at the same time. No interaction is expected if they are dosed separately for at least two hours.
The risk of muscle toxicity is increased when statins are administered concomitantly with nicotinic acid. In one study, Chinese patients receiving nicotinic acid and laropyrant co-administered with simvastatin were reported to have a higher incidence of myopathy and rhabdomyolysis compared to Caucasians.
Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, BMI>30kg/m², raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.
Pravastatin is contraindicated during pregnancy and should be administered to women of childbearing potential only when such patients are unlikely to conceive and have been informed of the potential risk. Special caution is recommended in adolescent females of childbearing potential to ensure proper understanding of the potential risk associated with pravastatin therapy during pregnancy. If a patient plans to become pregnant or becomes pregnant, the doctor has to be informed immediately and pravastatin should be discontinued because of the potential risk to the foetus.
A small amount of pravastatin is excreted in human breast milk, therefore pravastatin is contraindicated during breastfeeding.
Pravastatin has no or negligible influence on the ability to drive and use machines. However, when driving vehicles or operating machines, it should be taken into account that dizziness and visual disturbances may occur during treatment.
The frequencies of adverse events are ranked according to the following: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥/1000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Pravastatin has been studied at 40 mg in seven randomised double-blind placebo-controlled trials involving over 21,000 patients treated with pravastatin (n=10764) or placebo (n=10719), representing over 47,000 patients years of exposure to pravastatin. Over 19,000 patients were followed for a median of 4.8-5.9 years.
The following adverse drug reactions were reported; none of them occurred at a rate in excess of 0.3% in the pravastatin group compared to the placebo group.
Uncommon: dizziness, headache, sleep disturbance, insomnia.
Uncommon: vision disturbance (including blurred vision and diplopia).
Uncommon: dyspepsia/heartburn, abdominal pain, nausea/vomiting, constipation, diarrhoea, flatulence.
Uncommon: pruritus, rash, urticaria, scalp/hair abnormality (including alopecia), dermatomyositis.
Uncommon: abnormal urination (including dysuria, frequency, nocturia)
Uncommon: sexual dysfunction.
Uncommon: fatigue.
Effects on the skeletal muscle, e.g. musculoskeletal pain including arthralgia, muscle cramps, myalgia, muscle weakness and elevated CK levels have been reported in clinical trials. The rate of myalgia (1.4% pravastatin vs 1.4% placebo) and muscle weakness (0.1% pravastatin vs <0.1% placebo) and the incidence of CK level >3 x ULN and > 10 x ULN in CARE, WOSCOPS and LIPID was similar to placebo (1.6% pravastatin vs 1.6% placebo and 1.0% pravastatin vs 1.0% placebo, respectively).
Elevations of serum transaminases have been reported. In the three long-term, placebo-controlled clinical trials CARE, WOSCOPS and LIPID, marked abnormalities of ALT and AST (>3 x ULN) occurred at similar frequency (≤1.2%) in both treatment groups.
In addition to the above the following adverse events have been reported during post marketing experience of pravastatin:
Very rare: peripheral polyneuropathy, in particular if used for long period of time, paresthesia
Very rare: Hypersensitivity reactions: anaphylaxis, angioedema, lupus erythematous- like syndrome
Very rare: pancreatitis
Very rare: jaundice, hepatitis, fulminant hepatic necrosis
Very rare: rhabdomyolysis, which can be associated with acute renal failure secondary to myoglobinuria, myopathy myositis, polymyositis
Frequency not known: Immune-mediated necrotizing myopathy
Isolated cases of tendon disorders, sometimes complicated by rupture.
Class Effects:
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