Livalo Special Precautions

Precautions related to indications: Administration of this drug should be considered only after conducting a thorough physical examination and confirming the diagnosis is hypercholesterolemia or familial hypercholesterolemia.
Since there is no experience of use in homozygous cases of familial hypercholesterolemia, administration of this drug should be considered as a treatment supplementary to non-drug therapy such as LDL-apheresis only when treatment with this drug is judged indispensable.
Precautions related to dosage and administration: In the case of administration to patients with hepatic dysfunction, the starting dose should be 1 mg per day and the maximum dose should be 2 mg per day. [See Careful Administration as follows and Pharmacology: Pharmacokinetics under Actions.]
As the dose of this drug is increased, rhabdomyolysis-related adverse events may occur. When the dose is increased to 4 mg, attention should be given to the early signs of rhabdomyolysis such as CK (CPK) elevation, myoglobinuria, myalgia and weakness. (In overseas clinical studies, doses of 8 mg or above were discontinued due to several cases of rhabdomyolysis and related adverse events.)
Careful Administration (This product should be administered carefully to the following patients): Patients with hepatic dysfunction or alcoholism [Because this product is primarily distributed and acts in the liver, hepatic dysfunction may be aggravated. Furthermore, it has been reported that rhabdomyolysis is more likely to occur in alcoholic patients].
Patients with renal dysfunction or a history of renal dysfunction [It has been reported that many of the patients who had rhabdomyolysis also had renal dysfunction. Cases of acute aggravation deterioration of renal function accompanying rhabdomyolysis were also reported].
Patients who are receiving fibrates (such as bezafibrate) and niacin [Rhabdomyolysis is more likely to occur]. (See Interactions.)
Patients with hypothyroidism, hereditary muscular disorders (such as muscular dystrophy) or a family history of these, a history of drug-induced myopathy [It has been reported that rhabdomyolysis is more likely to occur].
Important General Precautions: When using this product, the followings should be carefully noted: Dietary advice should be given first, and then consider further exercise therapy and reduce the risk factors of ischemic heart disease such as hypertension and smoking.
Liver function tests should be performed once or more during the first 12 weeks of administration, and thereafter, periodically (once every 6 months, or more frequently).
The plasma lipid levels should be regularly tested during administration of this product. When the patient does not respond to therapy, administration of this drug should be discontinued.
Other precautions: It has been reported that there were immune-mediated necrotising myopathy characterised by proximal muscle weakness, elevated serum creatine kinase and necrotising myopathy without inflammation that persist despite discontinuation of statin treatment and improve with immunosuppressive agents.
In an oral administration study in dogs (≥ 3 mg/kg/day for 3 months, ≥ 1 mg/kg/day for 12 months), the development of cataracts was observed. However, no cataract was observed in other animals (rats, monkeys).
Use in Children: The safety of this drug in children has not been established (no clinical experience).
Use in the Elderly: Since elderly patients generally have reduced physiological function, careful supervision and measures such as reducing the dose is recommended. [It has been reported that rhabdomyolysis is more likely to occur in the elderly.]