PRAVASTATIN SODIUM

Prior to initiating Pravastatin sodium Tablets, secondary causes of hypercholesterolaemia should be excluded and patients should be placed on a standard lipid-lowering diet which should be continued during treatment. Pravastatin sodium tablets are taken orally once daily preferably in the evening with or without food.

Hypercholesterolaemia:

The recommended dose range is 10-40 mg 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 40mg.

Cardiovascular prevention:

In all preventive morbidity and mortality trials, the only studied starting and maintenance dose was 40mg daily. 5). 5).

Children:

The documentation on efficacy and safety in patients less than 18 years old is limited; therefore, the use of Pravastatin sodium tablets is not recommended in these patients.

Elderly patients:

There is no dose adjustment necessary in these patients unless there are predisposing risk factors (see section

The frequencies of adverse events are ranked according to the following: very common (≥ 1 / 10); common (≥1/100, <1/10); uncommon (≥1/1000 , <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000).

Clinical trials:

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

9 years. 3% in pravastatin sodium group compared to the placebo group. g. musculoskeletal pain including arthralgia, muscle cramps, myalgia, muscle weakness and elevated CK levels have been reported in clinical trials. 4% pravastatin sodium vs.

1% pravastatin sodium vs. 6% pravastatin sodium vs. 0% pravastatin sodium vs. ). Liver effects: elevations of serum transaminases have been reported. 2%) in both treatment groups. 6 mmol/L, BMI>30kg/m2, raised triglycerides, history of hypertension).

4) 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4 Muscle disorders).

Renal or hepatic impairment:

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.

g. cholestyramine, colestipol). 5). 5). 3 Contraindications - Hypersensitivity to the active substance or to any of the excipients. 4). 6). 4 Special warnings and precautions for use Pravastatin sodium has not been evaluated in patients with homozygous familial hypercholesterolaemia.

Therapy is not suitable for hypercholesterolaemia due to elevated HDL- Cholesterol. As for other HMG-CoA reductase inhibitors, combination of pravastatin sodium with fibrates is not recommended. There have been very rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with some statins.

IMNM is clinically characterised by persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.

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 sodium is administered to patients with a history of liver disease or heavy alcohol ingestion.

Muscle disorders:

As with others HMG-CoA Reductase inhibitors (statins), pravastatin sodium 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 patient-years), 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 drugs (due to lipophilicity and pharmacokinetic differences), including their dosage and potential for drug 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 medicines. 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.

5). When associated with statin therapy, muscle symptoms usually resolve following discontinuation of statin therapy.

Creatine kinase measurement and interpretation:

Routine monitoring of creatine kinase (CK) or other muscle enzyme levels is not recommended in asymptomatic patients on statin therapy. However, measurement of CK is recommended before starting statin therapy in patients with special predisposing factors, and in patients developing muscular symptoms during statin therapy, as described below.

If CK levels are significantly elevated at baseline (> 5 x ULN), CK levels should be remeasured about 5 to 7 days later to confirm the results. When measured, CK levels should be interpreted in the context of other potential factors that can cause transient muscle damage, such as strenuous exercise or muscle trauma.

Before treatment initiation:

Caution should be used in patients with predisposing factors such as renal impairment, hypothyroidism, previous history of muscular toxicity with a statin or fibrate, personal or familial history of hereditary muscular disorders, or alcohol abuse.

In these cases, CK levels should be measured prior to initiation of therapy. CK measurement should also be considered before starting treatment in persons over 70 years of age especially in the presence of other predisposing factors in this population.

If CK levels are significantly […]

Hypersensitivity to the active substance or to any of the excipients. 4). 6).