Ciprofibrate

Ciprofibrate is highly protein bound and therefore likely to displace other drugs from plasma protein binding sites. Ciprofibrate has been shown to potentiate the effect of warfarin, indicating that concomitant oral anticoagulant therapy should be given at reduced dosage and adjusted according to INR.

Although ciprofibrate may potentiate the effect of oral hypoglycaemics, available data do not suggest that such an interaction may be clinically significant.

As with other fibrates, the risk of myopathy, rhabdomyolysis and myoglobinuria may be increased if ciprofibrate is used in combination with HMG CoA reductase inhibitors. The benefits of combined use should be carefully weighed against the risks. Physicians contemplating concomitant therapy with HMG CoA reductase inhibitors should consult the SPC of the relevant HMG CoA reductase inhibitor as some higher doses are contraindicated/not recommended with fibrates.

Oestrogens can raise lipid levels. Although a pharmacodynamic interaction may be suggested, no clinical data are currently available.

Patients should be advised to report unexplained muscle pain, tenderness or weakness immediately.

CPK levels should be assessed immediately in patients reporting these symptoms. Therapy should be discontinued if myopathy is diagnosed or if markedly elevated CPK levels (levels exceeding 5 times the normal range) occur.

Doses of 200mg ciprofibrate per day or greater have been associated with a high risk of rhabdomyolysis. Therefore the daily dose should not exceed 100mg.

The risk of myopathy may be increased in the presence of the following predisposing factors:

• Impaired renal function and any situation of hypoalbuminaemia such as nephrotic syndrome
• hypothyroidism
• alcohol abuse
• age >70 years
• personal or family history of hereditary muscular disorders
• previous history of muscular toxicity with another fibrate

There is no evidence that ciprofibrate is teratogenic, but signs of toxicity at high doses were observed in teratogenicty tests in animals. As there are no data on its use in human pregnancy ciprofibrate is contraindicated during pregnancy.

Ciprofibrate is excreted in the breast milk of lactating rats. As there are no data on its use in lactation, ciprofibrate is contraindicated in nursing mothers.

Dizziness, somnolence, and fatigue have only rarely been reported in association with ciprofibrate. Patients should be warned that if they are affected they should not drive or operate machinery.