Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Hypercholesterolaemia
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. (see section 4.5)

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.

There have been rare post-marketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with pravastatin, promptly interrupt therapy. If an alternate etiology is not found do not restart pravastatin 
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 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 (see section 4.5).
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 4.5) When associated with statin therapy, muscle symptoms usually resolve following discontinuation of statin therapy.
(see section 4.5).

Pravastatin Teva 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 (see section 4.5). 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 Teva and fusidic acid should only be considered on a case by case basis and under close medical supervision.

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.

Cases of myopathy, including rhabdomyolysis, been reported with pravastatin coadministered with colchicine, and caution should be exercised when prescribing pravastatin with colchicine (see section 4.5).

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 remeasured 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.

Myasthenia gravis, ocular myasthenia

In few cases, statins have been reported to induce de novo or aggravate pre-existing myasthenia gravis or ocular myasthenia (see section 4.8). [Product name] should be discontinued in case of aggravation of symptoms. Recurrences when the same or a different statin was (re-) administered have been reported.


Interstitial lung disease
Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy (see section 4.8). 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>30kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

Lactose: this product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium: This medicine contains less than 23 mg sodium per tablet, that is to say essentially sodiu -free .

Effects on Driving

4.7 Effects on ability to drive and use machines

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.