Lopid

When LOPID (gemfibrozil) and lovastatin were used concomitantly there have been reports of severe myalgia, myositis and rhabdomyolysis accompanied by markedly elevated CK. When rhabdomyolysis is severe, the ensuing myoglobinuria can lead to acute renal failure. Therefore, lovastatin should not be used concomitantly with LOPID.

Abnormal liver function tests have been observed occasionally during LOPID administration, including elevations of AST, ALT, LDH, alkaline phosphatase, creatine kinase, and bilirubin. These are usually reversible when LOPID is discontinued. Therefore, periodic liver function studies are recommended and LOPID therapy should be terminated if abnormalities persist.

Mild hemoglobin, hematocrit and white blood cells (WBC) decrease have been observed occasionally following initiation of LOPID therapy. The levels then stabilize during long-term administration. Rarely, severe anemia, leukopenia, thrombocytopenia, eosinophilia and bone marrow hypoplasia have been reported. Therefore, periodic blood count determinations are recommended during the first 12 months of LOPID administration.

There have been reports of severe myalgia, myositis and rhabdomyolysis accompanied by markedly elevated creatine kinase (CK) when gemfibrozil and HMG-CoA reductase inhibitors, particularly cerivastatin were used concomitantly. When rhabdomyolysis is severe the ensuing myoglobinuria can lead to acute renal failure. Therefore, HMG-CoA reductase inhibitors should not be used concomitantly with LOPID (see Contraindications; Warnings, Muscle Effects).

Reduced bioavailability of LOPID may result when given simultaneously with resin-granule drugs such as colestipol. Administration of the drugs two hours or more apart is recommended.

Serious cases of hypoglycemia have been reported following the concomitant use of repaglinide and gemfibrozil. This is likely due to inhibition of CYP 2C8 by gemfibrozil as evidenced by decreases in blood glucose that were proportional to the dose of gemfibrozil. In healthy volunteers, the levels of repaglinide were significantly increased when co-administered with gemfibrozil. The averaged area under the curve (AUC) was increased 8-fold (range 6- to 15 fold) and the half-life increased 3 fold. When itraconazole, an inhibitor of CYP 3A4, was also given with gemfibrozil and repaglinide, even greater effects were observed: AUC for repaglinide was increased 19-fold and the half-life increased from 1.3 to 6 hours (see Contraindications).

CYP2C8 inhibition by gemfibrozil can affect the metabolism of several major cardiovascular drugs such as amiodarone, verapamil, warfarin but also other drugs such as tolbutamide.

Gemfibrozil is also known to potently inhibit CYP2C9 activity. Therefore, CYP2C9 inhibition by gemfibrozil can affect the metabolism of several major cardiovascular drugs such as carvedilol and losartan but also other drugs such as phenytoin and diazepam.

Before instituting LOPID (gemfibrozil) therapy, attempts should be made to control serum lipids and lipoproteins with appropriate diet, exercise, weight loss in obese patients, and control of diabetes mellitus.

Administration of approximately three and ten times the human dose to male rats for 10 weeks resulted in a dose-related decrease of fertility. Subsequent studies demonstrated that this effect was reversed after a drug-free period of about 8 weeks, and it was not transmitted to their offspring.

In patients with a past history of jaundice or hepatic disorder, LOPID should be used with caution.

Although no clinically significant abnormalities occurred that could be attributed to LOPID, the possibility exists that such abnormalities may occur.

Caution should be exercised when anticoagulants are given in conjunction with LOPID. The dosage of the anticoagulant should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin level has stabilized.

Because long-term administration of LOPID is recommended, pretreatment clinical chemistry studies should be performed to ensure that the patient has elevated serum lipid or low HDL cholesterol levels. Periodic determinations of serum lipids and lipoproteins should be done during LOPID administration, including measurement of LDL-cholesterol/HDL-cholesterol ratio, particularly in Type IV hyperlipoproteinemic patients.

Each maroon and white hard gelatin capsule printed “LOPID” in grey on body and printed “PD 669” in gray on cap contains: gemfibrozil 300 mg. Nonmedicinal ingredients: Capsule: cornstarch, polysorbate 80. Capsule shell: contains: silicon dioxide, FD&C Blue No. 1, FD&C Red No. 3, gelatin, sodium lauryl sulfate and titanium dioxide. Energy: 3.4 kJ (0.8 kcal). Gluten-, lactose-, paraben-, sodium-, sulfite- and tartrazine-free. Bottles of 100 and 250. Store at controlled room temperature (15 to 30°C).

Each white, ellipsoidal, film-coated tablet, imprinted in black ink “Lopid 600 mg” on one side and “Parke-Davis” on the other, contains: gemfibrozil 600 mg. Nonmedicinal ingredients: calcium stearate, candelilla wax, colloidal silicon dioxide, hypromellose, hydroxypropylcellulose, methylparaben, microcrystalline cellulose, Black Fine ink, polyethylene glycol, polysorbate 80, pregelatinized starch, propylparaben and white Opaspray. Energy: 2.0 kJ (0.47 kcal). Gluten-, lactose-, sodium-, sulfite- and tartrazine-free. Bottles of 100 and 250. Store at controlled room temperature (15 to 30°C).