PRAVASTATIN SODIUM

Posology Prior to initiating pravastatin, secondary causes of hypercholesterolemia should be excluded and patients should be placed on a standard lipid-lowering diet which should be continued during treatment. Hypercholesterolemia: the recommended dose range is 10 40 mg pravastatin sodium once daily.

The therapeutic response is seen within a week and the full effect of a given dose occurs within four weeks, therefore periodic lipid determinations should be performed and the dosage adjusted accordingly. The maximum daily dose is 40 mg pravastatin sodium.

Cardiovascular prevention: in all preventive morbidity and mortality trials, the only studied starting and maintenance dose was 40 mg daily. 5 Interaction with other medicinal products and other forms of interaction). 5 Interaction with other medicinal products and other forms of interaction).

1). 4). Renal or hepatic impairment: a starting dose of 10 mg pravastatin sodium 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.

g. cholestyramine, colestipol). 5 Interaction with other medicinal products and other forms of interaction). 5). For doses not realisable/practicable with this strength other strengths of this medicinal product are available. Methods of administration Pravastatin is administered orally once daily preferably in the evening with or without food.

Clinical trials Pravastatin has been studied at 40 mg in seven randomised double-blind placebo-controlled trials involving over 21000 patients treated with pravastatin (N=10764) or placebo (N=10719), representing over 47000 patients years of exposure to pravastatin.

9 years. 3% in the pravastatin group compared to the placebo group. 6 mmol/L, BMI>30kg/m 2, raised triglycerides, history of hypertension). g. musculoskeletal pain including arthralgia, muscle cramps, myalgia, muscle weakness and elevated CK levels have been reported in clinical trials.

4% pravastatin vs. 6% pravastatin vs. 4).

Liver effects:

Elevations of serum transaminases have been reported. 2%) in both treatment groups. Post marketing In addition to the above the following adverse reactions have been reported during post marketing experience of pravastatin. VERY RARE (<1/10000) including isolated reports NOT KNOWN Immune system disorders Hypersensitivity reactions like anaphylaxis, angioedema and lupus erythematous-like syndrome Nervous system disorders Peripheral polyneuropathy, in particular if used for a long period of time.

Paresthesia Myasthenia gravis Eye disorders Ocular myasthenia Gastrointestinal disorders Pancreatitis Hepato-biliary disorders Jaundice Hepatitis Fulminant hepatic necrosis Musculoskeletal, connective tissue and bone disorders Rhabdomyolysis, which can be associated with acute renal failure secondary to myoglobinuria*.

4 Special warnings and precautions for use. 6 mmol/L, BMI>30kg/m2, raised triglycerides, history of hypertension). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Pravastatin has not been evaluated in patients with homozygous familial hypercholesterolemia. Therapy is not suitable when hypercholesterolemia is due to elevated HDL-Cholesterol. As for other HMG-CoA reductase inhibitors, combination of pravastatin with fibrates is not recommended.

In children before puberty, the benefit/risk of treatment should be carefully evaluated by physicians before treatment initiation. Hepatic disorders: as with other lipid-lowering agents, moderate increases in liver transaminase levels have been observed.

In the majority of cases, liver transaminase levels have returned to their baseline value without the need for treatment discontinuation. Special attention should be given to patients who develop increased transaminase levels and therapy should be discontinued if increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) exceed three times the upper limit of normal and persist.

Caution should be exercised when pravastatin is administered to patients with a history of liver disease or heavy alcohol ingestion. 8). Presenting features can include dysponea, non-productive cough and deterioration in general health (fatigue, weight loss and fever).

If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued. Muscle disorders: as with other HMG-CoA Reductase inhibitors (statins), pravastatin has been associated with the onset of myalgia, myopathy and very rarely, rhabdomyolysis.

Myopathy must be considered in any patient under statin therapy presenting with unexplained muscle symptoms such as pain or tenderness, muscle weakness, or muscle cramps. In such cases creatine kinase (CK) levels should be measured (see below).

Statin therapy should be temporarily interrupted when CK levels are > 5 x ULN or when there are severe clinical symptoms. Very rarely (in about 1 case over 100 000 patientyears), rhabdomyolysis occurs, with or without secondary renal insufficiency.

Rhabdomyolysis is an acute potentially fatal condition of skeletal muscle which may develop at any time during treatment and is characterised by massive muscle destruction associated with major increase in CK (usually > 30 or 40 x ULN) leading to myoglobinuria.

The risk of myopathy with statins appears to be exposure-dependent and therefore may vary with individual medicinal products (due to lipophilicity and pharmacokinetic differences), including their dosage and potential for medicinal product interactions.

Although there is no muscular contraindication to the prescription of a statin, certain predisposing factors may increase the risk of muscular toxicity and therefore justify a careful evaluation of the benefit/risk and special clinical monitoring.

CK measurement is indicated before starting statin therapy in these patients (see below). The risk and severity of muscular disorders during statin therapy is increased by the co-administration of interacting medicinal products. The use of fibrates alone is occasionally associated with myopathy.

The combined use of a statin and fibrates should generally be avoided. The co-administration of statins and nicotinic acid should be used with caution. An increase in the incidence of myopathy has also been described in patients receiving other statins in combination with inhibitors of cytochrome P450 metabolism.

This may result from pharmacokinetic interactions that have not been documented for pravastatin (see section

1. 4). 6).