Cardiovascular System-Hypolipidemic agents
= Additional active ingredients
PRESENTATION AND DOSSAGE
CAPS: 30 x 100 mg.
Primary hyperlipidemia resistant to appropriate dietary management, including hypercholesterolemia, hypertryglyceridaem., combined hyperlipidemia (types 11a, 11b, III, IV).
Severe hepatic impairment, Severe renal impairment, Hypersensitivity to the active substance or to one of the excipients, Pregnancy and lactation, Concurrent use with another fibrate.
Warnings : Muscle damage, including rhabdomyolysis in exceptional cases, has been reported with fibrates. Patients should be advised to report unexplained muscle pain, tenderness or weakness immediately. CPK levels should be assessed immediately in patients reporting these symptoms and therapy should be discontinued if myopathy is diagnosed or if markedly elevated CPK of muscle origin occurs (more than 5 times normal levels).
Any situation of renal insufficiency or hypoalbuminaemia such as nephritic syndrome may increase the risk of myopahty. Muscle related events appear to be dose related and therefore the daily dosage should not exceed 100mg. Use in caution in patients with impaired hepatic function. In addition, the risk of muscle damage may be increased in the event of combination with another fibrate or with an HMG-CoA reductase inhibitor. An underlying hypothyroidism may cause a secondary dyslipidaemia and therefore should be diagnosed and corrected prior to any drug treatment. Furthermore, hypothyroidism may be a risk factor for myopathy. Due to the presence of lactose, this medicinal product is contraindicated in the event of congenital galactosaemia, glucose and galactose malabsorption syndrome or lactase deficiency.
Special precautions for use :
In children, since the long-term safety has not been demonstrated and the specific effects on the development of a growing body are unknown, use should only be considered in the event of severe lipid disorders which are sensitive to treatment.
If a satisfactory reduction in serum lipid concentrations is not achieved within a period of a few months (3 to 6 months), additional or different methods of treatment should be considered. Periodic hepatic function tests are recommended (every 3 months for the first 12 months of treatment). Ciprofibrate treatment should be discontinued if significant transaminases abnormalities persist (elevation of ASAT and ALAT to more than 3 times the normal upper limit) or if cholestatic liver injury is evidenced.
Use with caution in patients with impaired renal function.
In the event of concomitant treatment with oral anticoagulants, the prothrombin rate, expressed by the INR, must be measured.
Secondary causes of dyslipidemia, such as hypothyroidism, should be excluded or corrected prior to commencing any lipid lowering drug treatment.
Association with oral anticoagulant therapy: concomitant oral anticoagulant therapy should be given at reduced dosage and adjusted according to INR.
Muscle disorders: as with other fibrates, cases of muscle damage (diffuse myalgia,myopathy including myositis, painful sensitivity, weakness), along with exceptionalcases of rhabdomyolysis, sometimes severe, have been reported. These are usually reversible when treatment is discontinued.
Effects occurring at the start of treatment and less common thereafter:
Digestive or gastrointestinal disorders, such as nausea, vomiting, dyspepsia, diarrhea,
abdominal discomfort. Generally, these side effects were mild to moderate in nature and
occurred early on, becoming less frequent as treatment progressed. Headaches, vertigo, dizziness, rare cases of drowsiness, fatigue or sleeping disorders.
Other undesirable effects have also been reported.
Skin reactions: pruritus, urticaria, rash, eczema, photosensitivity reactions in exceptional
cases (as with other fibrates), alopecia.
Blood and lymphatic system disorder: Thrombocytopenia- Frequency not known.
As with other fibrates, uncommon cases of elevated transaminase levels have been observed. Very rare cases of cholestasis or cytolysis have also been reported.
As with other medicinal products in this class, a few cases of impotence have been reported.
Isolated cases of interstitial pneumopathy and/or pulmonary fibrosis have beenreported.
General disorders: Fatigue has only rarely been reported in association with ciprofibrate. At present, no controlled studies are available enabling assessment of the long-term undesirable effects in general and, more specifically, the risk of cholelithiasis. However, isolated cases of cholelithiasis have been reported.
Contra-indicated combination Other fibrates: As with other fibrates, the risk of myopathy, rhabdomyolysis andmyoglobinuria may be increased if ciprofibrate is used in combination with HMG CoAreductase inhibitors.
Inadvisable combination+ HMG-CoA reductase inhibitors (statins) and other fibrates: 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 carfully 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.
Combination requiring for precautions for use: Oral anticoagulants: Increased effect of the oral anticoagulant and increased haemorrhagic risk (due to displacement of plasma protein binding sites). More frequent monitoring of prothrombin rate and monitoring of INR. Adjustment of oral anticoagulant dosage during treatment with Lipanor and for 8 days after its discontinuation
Combination to be taken into account+ Oral hypoglycaemics: Although ciprofibrate may potentiate the effect of oral hypoglycaemics, available data do not suggest that such an interaction will cause clinically significant problems.
Oesrogens : Oestrogens can raise lipid levels. Although pharmacodynamic interaction, no clinical data are currently available.
Adults: The recommended dosage is 100 mg per day. This dose should not be exceeded.
Elderly patients: As for adults, but carefully observe “Precautions”.
Children: Not recommended since safety and efficacy in children have not been established.
Use in impaired renal function: In moderate renal impairment it is recommended that dosage be reduced to one capsule every other day. Patients should be carefully monitored. Ciprofibrate should not be used in severe renal impairment In combination with dietary measures, this medicinal product is a long-term symptomatic treatment, in which efficacy must be periodically monitored.
For full details see prescribing information.
There are rare reports of overdose with ciprofibrate but in these cases there are no adverse events that are specific to overdosage. There are no specific antidotes to ciprofibrate. Treatment of overdosage should be symptomatic. Gastric lavage and appropriate supportive care may be instituted if necessary. Ciprofibrate is non- dialyzable.
PREGNANCY & LACTATION
There is no evidence that ciprofibrate is teratogenic but signs of toxicity at high doseswere observed in teratogenisity tests in animals and ciprofibrate is excreted in the breastmilk of lactating rats. As there are no data on its use in human pregnancy and lactation,ciprofibrate is contra-indicated during pregnancy and in nursing mothers.
MANUFACTURER & DISTRIBUTER:
License Holder: CTS Chemical Ind. Ltd.