Pravastatin STELLA 20 mg

Rx

Indications

• Treatment of primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet, when response to diet and other non-pharmacological treatments (eg. exercise, weight reduction) is inadequate.
• Reduction of cardiovascular mortality and morbidity in patients with moderate or severe hypercholesterolaemia and at high risk of a first cardiovascular event, as an adjunct to diet.
• Reduction of cardiovascular mortality and morbidity in patients with a history of myocardial infarction or unstable angina pectoris and with either normal or increased cholesterol levels, as an adjunct to correction of other risk factors.
• Reduction of post transplantation hyperlipidaemia in-patient receiving immunosuppressive therapy following solid organ transplantation.

Dosage

• 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 40 mg.
• Cardiovascular prevention
  In all preventive morbidity and mortality trials, the only studied starting and maintenance dose was 40 mg daily.
• Dosage after transplantation
  Following organ transplantation a starting dose of 20 mg per day is recommended in patients receiving immunosuppressive therapy.
  Depending on the response of the lipid parameters, the dose may be adjusted up to 40 mg under close medical supervision.
• Children and adolescents (8 – 18 years of age) with heterozygous familial hypercholesterolaemia
  The recommended dose range is 10 – 20 mg once daily between 8 and 13 years of age as doses greater than 20 mg have not been studied in this population and 10 – 40 mg daily between 14 and 18 years of age.
• Elderly patients
  There is no dose adjustment necessary in these patients unless there are predisposing risk factors.
• 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.
• Concomitant therapy
  The lipid lowering effects of pravastatin sodium on total cholesterol and LDL-cholesterol are enhanced when combined with a bile acid-binding resin (e.g. colestyramine, colestipol). Pravastatin sodium should be given either one hour before or at least four hours after the resin.
  For patients taking ciclosporin with or without other immunosuppressive medicinal products, treatment should begin with 20 mg of pravastatin sodium once daily and titration to 40 mg should be performed with caution.
  The risk of muscle injury increases when certain other medications are taken with statins: Gemfibrozil, blood cholesterol-lowering agents of other fibrates, lipid-lowering high doses of niacin (> 1 g/day), colchicine.
  Co-administration of HIV or hepatitis C (HCV) protease inhibitors and cholesterol-lowering statin drugs can increase the risk of muscle injury. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.

Usage

• Prior to initiating Pravastatin STELLA 20 mg, 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 is administered orally once daily preferably in the evening with or without food.

• Hypersensitivity to the active substance or to any of the excipients.
• Active liver disease or unexplained, persistent elevations of serum transaminase elevation exceeding 3 times the upper limit of normal (ULN).
• Pregnancy and lactation.

Uncommon

• Dizziness, headache, sleep disturbance, insomnia.
• Vision disturbance (including blurred vision and diplopia).
• Dyspepsia/heartburn, abdominal pain, nausea/vomiting, constipation, diarrhoea, flatulence.
• Pruritus, rash, urticaria, scalp/hair abnormality (including alopecia), dermatomyositis.
• Abnormal urination (including dysuria, frequency, nocturia).
• Sexual dysfunction.
• Fatigue.

• Pravastatin has not been evaluated in patients with homozygous familial hypercholesterolaemia. Therapy is not suitable when hypercholesterolaemia is due to elevated HDL-cholesterol.
• As for other HMG-CoA reductase inhibitors, combination of pravastatin with fibrates is not recommended.
• Pravastatin must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.
  Statin therapy may be re-introduced seven days after the last dose of fusidic acid.
  In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of pravastatin sodium and fusidic acid should only be considered on a case by case basis and under close medical supervision.
• In children before puberty, the benefit/risk of treatment should be carefully evaluated by physicians before treatment initiation.
• Hepatic disorders
  Liver enzyme testing is recommended prior to initiating statin therapy and in cases where clinical indications require testing thereafter.
  As with other lipid – lowering agents, moderate increases in liver transaminase levels has 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.
• 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. 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.
  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. This may result from pharmacokinetic interactions that have not been documented for pravastatin. When associated with statin therapy, muscle symptoms usually resolve following discontinuation of statin therapy.
  There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or after treatment with some statins. IMNM is clinically characterized by persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.
• 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 re-measured 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 elevated (> 5 x ULN) at baseline, treatment should not be started and the results should be re-measured after 5 – 7 days. The baseline CK levels may also be useful as a reference in the event of a later increase during statin therapy.
  During treatment:
  Patients should be advised to report promptly unexplained muscle pain, tenderness, weakness or cramps. In these cases, CK levels should be measured. If a markedly elevated (> 5 x ULN) CK level is detected, statin therapy must be interrupted. Treatment discontinuation should also be considered if the muscular symptoms are severe and cause daily discomfort, even if the CK increase remains ≤ 5 x ULN. If symptoms resolve and CK levels return to normal, then reintroduction of statin therapy may be considered at the lowest dose and with close monitoring. If a hereditary muscular disease is suspected in such patients, restarting statin therapy is not recommended.
• Interstitial lung disease
  Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, 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.
• Diabetes mellitus
  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 > 30 kg/m², raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.
• Pravastatin STELLA 20 mg contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Concomitant therapy
  The risk of muscle injury increases when certain other medications are taken with statins: Gemfibrozil, blood cholesterol-lowering agents of other fibrates, lipid-lowering high doses of niacin (> 1 g/day), colchicine.
  Co-administration of HIV or hepatitis C (HCV) protease inhibitors and cholesterol-lowering statin drugs can increase the risk of muscle injury. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.
• 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.
• 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.