Muscle Effects: In common with other HMG-CoA reductase inhibitors (statins), there is the potential for myalgia, myopathy and, rarely, rhabdomyolysis to develop. Patients should be asked to report any muscle symptoms. Creatine kinase (CK) levels should be measured in any patient reporting muscle pain, muscle tenderness or weakness especially if accompanied by malaise or fever.
Creatine kinase should not be measured following strenuous exercise or in the presence of any other plausible cause of CK increase which may confound interpretation of the result. When elevated CK concentrations (>5x ULN) are noted, a confirmatory test should be performed within 5 to 7 days. 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; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
LIVALO 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 Interactions). 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 LIVALO and fusidic acid should only be considered on a case by case basis and under close medical supervision.
Before Treatment: In common with other statins, LIVALO should be prescribed with caution in patients with pre-disposing factors for rhabdomyolysis. A creatinine kinase level should be measured, to establish a reference baseline, in the following situations: renal impairment, hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with a fibrate or another statin, history of liver disease or alcohol abuse, elderly patients (over 70 years) with other predisposing risk factors for rhabdomyolysis.
In such situations, clinical monitoring is recommended and the risk of treatment should be considered in relation to the possible benefit. Treatment with LIVALO should not be started if CK values are >5x ULN.
During Treatment: Patients must be encouraged to report muscle pain, weakness or cramps immediately. Creatine kinase levels should be measured and treatment stopped if CK levels are elevated (>5x ULN). Stopping treatment should be considered if muscular symptoms are severe even if CK levels are ≤5x ULN. If symptoms resolve and CK levels return to normal, then re-introduction of LIVALO may be considered at a dose of 1mg and with close monitoring.
Liver Effects: In common with other statins, LIVALO should be used with caution in patients with a history of liver disease or who regularly consume excessive quantities of alcohol. Liver function tests should be performed prior to initiating treatment with LIVALO and then periodically during treatment. LIVALO treatment should be discontinued in patients who have a persistent increase in serum transaminases (ALT and AST) exceeding 3x ULN.
Renal Effects: LIVALO should be used with caution in patients with moderate or severe renal impairment. Dose increments should be instituted only with close monitoring. In those with severe renal impairment, 4mg dose is not recommended (see Dosage & Administration).
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 of hyperglycaemia (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. However, there has been no confirmed signal of a diabetes risk for pitavastatin either in post-marketing safety surveillance studies or in prospective studies (see Pharmacology: Pharmacodynamics under Actions).
Interstitial Lung Disease: Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy (see Adverse Reactions). 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.
Other effects: A temporary suspension of LIVALO is recommended for the duration of treatment with erythromycin, other macrolide antibiotics or fusidic acid (see Interactions). LIVALO should be used with caution in patients taking drugs known to cause myopathy (e.g. fibrates or niacin, see Interactions).
The tablets contain lactose. Patients with the rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in Children: There is limited data on the long term effect on growth and sexual maturation in paediatric patients 6 years of age or older taking LIVALO. Adolescent females should be counselled on appropriate contraceptive precautions during treatment with LIVALO (see Contraindications, Use in Pregnancy & Lactation).
Effects on ability to drive and use machines: There is no pattern of adverse events that suggests that patients taking LIVALO will have any impairment of ability to drive and use hazardous machinery, but it should be taken into account that there have been reports of dizziness and somnolence during treatment with LIVALO.