Fenofibrate 100 & 200 mg capsule
Category:
Antihyperlipidemic
(USPDI)
Chemistry:
Chemical name: propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate. The molecular formula is C20H21ClO4, representing a molecular weight of 360.8 g/mol. It has the following structural formula:
(Pubchem)
Pharmacokinetics:
Absorption:
Maximum plasma concentrations (Cmax) occur within 4 to 5 hours after oral administration.
The absorption of fenofibrate is increased when administered with food.
Distribution:
Fenofibric acid is strongly bound to plasma albumin (more than 99%).
Metabolism and excretion:
After oral administration, fenofibrate is rapidly hydrolised by esterases to the active metabolite fenofibric acid.
Fenofibrate is not a substrate for CYP 3A4. No hepatic microsomal metabolism is involved.
Excretion:
The drug is excreted mainly in the urine. mainly in the form of fenofibric acid and its glucuronoconjugate. Elimination half-life of fenofibric acid is approximately 20 hours and is not eliminated during haemodialysis.
(www.medicines.org.uk)
Indications:
It is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, weight reduction) for the following:
- Treatment of severe hypertriglyceridaemia with or without low HDL cholesterol.
- Mixed hyperlipidaemia when a statin is contraindicated or not tolerated and in patients at high cardiovascular risk in addition to a statin when triglycerides and HDL cholesterol are not adequately controlled.
(www.medicines.org.uk)
Contraindications:
- Hepatic insufficiency (including biliary cirrhosis and unexplained persistent liver function abnormality), Known gallbladder disease, Severe renal insufficiency, Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia, Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen.
- Hypersensitivity to the active substance or to any of the excipients.
Warnings & Precautions:
- Uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, pharmacological treatment, alcoholism, should be adequately treated before fenofibrate therapy is considered.
- Inform your physician or pharmacist if using diuretics, β-blocking agents, estrogens, progestogens, combined oral contraceptives, immunosuppressive agents and protease inhibitors.
- It is recommended that transaminase levels are monitored every 3 months during the first 12 months of treatment and thereafter periodically. When symptoms indicative of hepatitis occur (e.g. jaundice, pruritus), and diagnosis is confirmed by laboratory testing, fenofibrate therapy should be discontinued.
- Inform your physician if you have personal or familial history of hereditary muscular disorders, renal impairment, hypothyroidism and high alcohol intake, age above 70 years.
- Consult your physician or pharmacist if presenting diffuse myalgia, myositis, muscular cramps and weakness and/or marked increases in CPK (levels exceeding 5 times the normal range). In such cases treatment with fenofibrate should be stopped.
- The co-prescription of fenofibrate with a HMG-CoA reductase inhibitor or another fibrate should be reserved to patients with severe combined dyslipidaemia and high cardiovascular risk without any history of muscular disease and a close monitoring of potential muscle toxicity.
- It should be used with caution in patients with mild to moderate renal insufficiency.
- It is recommended that creatinine is measured during the first 3 months after initiation of treatment and periodically thereafter.
- Regularly visit your physician.
(www.medicines.org.uk)
Pregnancy and Breast – feeding:
Pregnancy
Fenofibrate should only be used during pregnancy after a careful benefit/risk assessment.
Breastfeeding
It should not be used during breast-feeding.
(www.medicines.org.uk, PDR.net)
Drug Interactions:
- Oral anti-coagulant, Cyclosporin, HMG-CoA reductase inhibitors or Other Fibrates, Glitazones,
CYP2C19, CYP2A6, and especially CYP2C9 metabolised drugs with a narrow therapeutic index,
- In common with other fibrates, fenofibrate induces microsomal mixed-function oxidases involved in fatty acid metabolism in rodents and may interact with drugs metabolised by these enzymes.
Adverse Reactions:
Gastrointestinal signs and symptoms (abdominal pain, nausea, vomiting, diarrhoea, flatulence), Transaminases increased, Blood homocysteine level increased, Headache, Thromboembolism (pulmonary embolism, deep vein thrombosis), Pancreatitis, Cholelithiasis, Cutaneous hypersensitivity (e.g. Rashes, pruritus, urticaria), Muscle disorder (e.g. myalgia, myositis, muscular spasms and weakness), Sexual dysfunction, Blood creatinine increased, Fatigue.
(www.medicines.org.uk)
OVERDOSE:
In the majority of cases no overdose symptoms were reported.
No specific antidote is known. If overdose is suspected, treat symptomatically and do supportive measures if required.
(www.medicines.org.uk)
DOSAGE AND ADMINISTRATION:
Dietary measures initiated before therapy should be continued. Response to therapy should be monitored by determination of serum lipid values. If an adequate response has not been achieved after several months (e.g. 3 months), complementary or different therapeutic measures should be considered.
Adults:
Initially, 100 -200 mg PO once daily, administered whit a meal. Evaluate lipid serum concentration at 4-8 week intervals. Maximum dosage is 200 mg PO once daily. Consider dosage reduction if serum lipid concentrations fall significantly below target goals.
Special populations
- patients with mild to moderate renal insufficiency, the dose of fenofibrate should not exceed 100 mg standard or 67 mg micronized once daily.
- Fenofibrate 100 & 200 mg are not recommended for use in patients with hepatic impairment.
- The use of fenofibrate is not recommended in paediatric subjects under 18 years.
(PDR.net ,www.medicines.org.uk)
Storage:
Store below 30˚ C and keep away from humidity & light.
How supplied:
Fenofibrate 100 & 200 mg hard-gelatin capsules contain 100 & 200 mg micronized Fenofibrate and are available in Pink-Brown-color capsules and White-color capsules respectively in boxes of 50 capsules with leaflet for Fenofibrate 100 mg capsule, and in boxes of 30 & 60 capsules with leaflet for Fenofibrate 200 mg capsule, manufactured at Tehran darou pharmaceutical co.
References:
1) medicines.org.uk 2021
2) USPDI 2007
3) www.PDR.net 2021
4) Pubchem 2021