What happens if I overdose Lipil?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of Lipil capsules:
Store Lipil capsules at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Lipil capsules out of the reach of children and away from pets.
Overdose of Lipil in details
Only anecdotal cases of Lipil overdosage have been reported. In the majority of cases, no overdose symptoms were reported.
There is no specific treatment for overdose with Lipil. General supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because Lipil is highly bound to plasma proteins, hemodialysis should not be considered.
What should I avoid while taking Lipil?
If you also take cholestyramine, colesevelam, or colestipol: Wait 4 to 6 hours after taking any of these other medicines before you take Lipil. Avoid taking Lipil within 1 hour before taking the other medicine.
Avoid drinking alcohol. It can raise triglyceride levels, and may also damage your liver while you are taking Lipil.
Lipil warnings
Mortality and Coronary Heart Disease Morbidity
The effect of Lipil on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. Because of similarities between Lipil and Lipil, clofibrate, and gemfibrozil, the findings in the following large randomized, placebo-controlled clinical studies with these fibrate drugs may also apply to Lipil.
The Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial was a randomized placebo-controlled study of 5518 patients with type 2 diabetes mellitus on background statin therapy treated with Lipil. The mean duration of follow-up was 4.7 years. Lipil plus statin combination therapy showed a non-significant 8% relative risk reduction in the primary outcome of major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular disease death (hazard ratio [HR] 0.92, 95% CI 0.79-1.08) (p=0.32) as compared to statin monotherapy. In a gender subgroup analysis, the hazard ratio for MACE in men receiving combination therapy versus statin monotherapy was 0.82 (95% CI 0.69-0.99), and the hazard ratio for MACE in women receiving combination therapy versus statin monotherapy was 1.38 (95% CI 0.98-1.94) (interaction p=0.01). The clinical significance of this subgroup finding is unclear.
The Lipil Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year randomized, placebo-controlled study of 9795 patients with type 2 diabetes mellitus treated with Lipil. Lipil demonstrated a non-significant 11% relative reduction in the primary outcome of coronary heart disease events (hazard ratio [HR] 0.89, 95% CI 0.75-1.05, p = 0.16) and a significant 11% reduction in the secondary outcome of total cardiovascular disease events (HR 0.89 [0.80-0.99], p = 0.04). There was a non-significant 11% (HR 1.11 [0.95, 1.29], p = 0.18) and 19% (HR 1.19 [0.90, 1.57], p = 0.22) increase in total and coronary heart disease mortality, respectively, with Lipil as compared to placebo.
In the Coronary Drug Project, a large study of post-myocardial infarction patients treated for 5 years with clofibrate, there was no difference in mortality seen between the clofibrate group and the placebo group. There was, however, a difference in the rate of cholelithiasis and cholecystitis requiring surgery between the two groups (3.0% vs. 1.8%).
In a study conducted by the World Health Organization (WHO), 5000 subjects without known coronary artery disease were treated with placebo or clofibrate for 5 years and followed for an additional one year. There was a statistically significant, higher age-adjusted all-cause mortality in the clofibrate group compared with the placebo group (5.70% vs. 3.96%, p = < 0.01). Excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. This appeared to confirm the higher risk of gallbladder disease seen in clofibrate-treated patients studied in the Coronary Drug Project.
The Helsinki Heart Study was a large (N = 4081) study of middle-aged men without a history of coronary artery disease. Subjects received either placebo or gemfibrozil for 5 years, with a 3.5 year open extension afterward. Total mortality was numerically higher in the gemfibrozil randomization group but did not achieve statistical significance (p = 0.19, 95% confidence interval for relative risk G:P = 0.91-1.64). Although cancer deaths trended higher in the gemfibrozil group (p = 0.11), cancers (excluding basal cell carcinoma) were diagnosed with equal frequency in both study groups. Due to the limited size of the study, the relative risk of death from any cause was not shown to be different than that seen in the 9 year follow-up data from WHO study (RR = 1.29). A secondary prevention component of the Helsinki Heart Study enrolled middle-aged men excluded from the primary prevention study because of known or suspected coronary heart disease. Subjects received gemfibrozil or placebo for 5 years. Although cardiac deaths trended higher in the gemfibrozil group, this was not statistically significant (hazard ratio 2.2, 95% confidence interval: 0.94-5.05).
Skeletal Muscle
Fibrates increase the risk of myositis or myopathy and have been associated with rhabdomyolysis. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal failure, or hypothyroidism.
Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevations of CPK levels. Patients should promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and Lipil should be discontinued if markedly elevated CPK levels occur or myopathy or myositis is suspected or diagnosed.
Data from observational studies suggest that the risk for rhabdomyolysis is increased when fibrates are co-administered with a statin.
Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered with colchicine, and caution should be exercised when prescribing Lipil with colchicine.
Liver Function
Lipil at a dose of 135 mg once daily has been associated with increases in serum transaminases [AST (SGOT) or ALT (SGPT)]. In a pooled analysis of three 12-week, double-blind, controlled studies of Lipil, increases in ALT and AST to > 3 times the upper limit of normal on two consecutive occasions occurred in 1.9% and 0.2%, respectively, of patients receiving Lipil without other lipid-altering drugs. Increases in ALT and/or AST were not accompanied by increases in bilirubin or clinically significant increases in alkaline phosphatase.
In a pooled analysis of 10 placebo-controlled trials of Lipil, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking Lipil versus 1.1% of patients treated with placebo. The incidence of increases in transaminases observed with Lipil therapy may be dose related. In an 8-week dose-ranging study of Lipil in hypertriglyceridemia, the incidence of ALT or AST elevations ≥ 3 times the upper limit of normal was 13% in patients receiving dosages equivalent to 90 mg to 135 mg Lipil once daily and was 0% in those receiving dosages equivalent to 45 mg Lipil once daily or less, or placebo. Hepatocellular, chronic active, and cholestatic hepatitis observed with Lipil therapy have been reported after exposures of weeks to several years. In extremely rare cases, cirrhosis has been reported in association with chronic active hepatitis.
Baseline and regular monitoring of liver function, including serum ALT (SGPT) should be performed for the duration of therapy with Lipil, and therapy discontinued if enzyme levels persist above 3 times the upper limit of normal.
Serum Creatinine
Reversible elevations in serum creatinine have been reported in patients receiving Lipil as well as patients receiving Lipil. In the pooled analysis of three 12-week, double-blind, controlled studies of Lipil, increases in creatinine to > 2 mg/dL occurred in 0.8% of patients treated with Lipil without other lipid-altering drugs. Elevations in serum creatinine were generally stable over time with no evidence for continued increases in serum creatinine with long-term therapy and tended to return to baseline following discontinuation of treatment. The clinical significance of these observations is unknown. Monitoring renal function in patients with renal impairment taking Lipil is suggested. Renal monitoring should be considered for patients at risk for renal insufficiency, such as the elderly and those with diabetes.
Cholelithiasis
Lipil, like Lipil, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Lipil therapy should be discontinued if gallstones are found.
Coumarin Anticoagulants
Caution should be exercised when Lipil is given in conjunction with oral coumarin anticoagulants. Lipil may potentiate the anticoagulant effects of these agents resulting in prolongation of the prothrombin time/International Normalized Ratio (PT/INR). Frequent monitoring of PT/INR and dose adjustment of the oral anticoagulant are recommended until the PT/INR has stabilized in order to prevent bleeding complications.
Pancreatitis
Pancreatitis has been reported in patients taking drugs of the fibrate class, including Lipil. This occurrence may represent a failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with obstruction of the common bile duct.
Hematological Changes
Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following initiation of Lipil and Lipil therapy. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with fenofibrates. Periodic monitoring of red and white blood cell counts are recommended during the first 12 months of Lipil administration.
Hypersensitivity Reactions
Acute hypersensitivity reactions such as Stevens-Johnson syndrome and toxic necrolysis requiring patient hospitalization and treatment with steroids have been reported in individuals treated with fenofibrates.
Venothromboembolic Disease
In the FIELD trial, pulmonary embolus (PE) and deep vein thrombosis (DVT) were observed at higher rates in the Lipil- than the placebo-treated group. Of 9,795 patients enrolled in FIELD, there were 4,900 in the placebo group and 4,895 in the Lipil group. For DVT, there were 48 events (1%) in the placebo group and 67 (1%) in the Lipil group (p = 0.074); and for PE, there were 32 (0.7%) events in the placebo group and 53 (1%) in the Lipil group (p = 0.022).
In the Coronary Drug Project, a higher proportion of the clofibrate group experienced definite or suspected fatal or nonfatal PE or thrombophlebitis than the placebo group (5.2% vs. 3.3% at five years; p < 0.01).
Paradoxical Decreases in HDL Cholesterol Levels
There have been postmarketing and clinical trial reports of severe decreases in HDL cholesterol levels (as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibrate therapy. The decrease in HDL-C is mirrored by a decrease in apolipoprotein A1. This decrease has been reported to occur within 2 weeks to years after initiation of fibrate therapy. The HDL-C levels remain depressed until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is rapid and sustained. The clinical significance of this decrease in HDL-C is unknown. It is recommended that HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline, and fibrate therapy should not be re-initiated.
What should I discuss with my healthcare provider before taking Lipil?
Some medical conditions may interact with CIP - Lipil. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
- if you are pregnant, planning to become pregnant, or are breast-feeding
- if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
- if you have allergies to medicines or other substances
- if you have a history of diabetes, an underactive thyroid, heart problems (eg, heart blood vessel problems), gallbladder problems (eg, gallstones), pancreatitis, kidney or liver problems, or muscle problems
- if you have a history of blood clots in your veins (deep vein thrombosis or pulmonary embolism)
- if you are very overweight, have an inactive lifestyle, have a poor diet, or you drink alcohol or have a history of alcohol abuse
- if you have trouble swallowing
- if you are taking a beta-blocker (eg, propranolol), estrogen, or thiazide diuretic (eg, hydrochlorothiazide)
Some MEDICINES MAY INTERACT with CIP - Lipil. Tell your health care provider if you are taking any other medicines, especially any of the following:
- Colchicine or HMG-CoA reductase inhibitors (statins) (eg, simvastatin) because the risk of serious muscle problems may be increased
- Immunosuppressants (eg, cyclosporine) or other medicines that may harm the kidney (eg, aminoglycoside antibiotics [eg, gentamicin], amphotericin B, nonsteroidal anti-inflammatory drugs [NSAIDs] [eg, ibuprofen], tacrolimus, vancomycin) because they may increase the risk of CIP - Lipil's side effects. Ask your doctor if you are unsure if any of your medicines might harm the kidney
- Anticoagulants (eg, warfarin) because the risk of their side effects may be increased by CIP - Lipil
This may not be a complete list of all interactions that may occur. Ask your health care provider if CIP - Lipil may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Lipil precautions
Cross-Sensitivity and/or Related Problems: Lipil has chemical, pharmacological and clinical similarities to other fibrate agents, clofibrate and gemfibrozil.
Carcinogenicity: A 24-month study in rats given Lipil doses of 10, 45 and 200 mg/kg of body weight, resulted in a significant increase in the incidence of liver carcinomas in both male and female rats given 200 mg/kg dose.
Mutagenicity: Lipil was not found to be mutagenic in the Ames test and mouse lymphoma, chromosomal aberration and unscheduled DNA synthesis tests.
Use in pregnancy: Adequate and well-controlled studies in pregnant women have not been done. Lipil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lipil has been shown to be embryocidal and teratogenic in rats given 7-10 times the maximum recommended human dose (MRHD) of Lipil on mg/m2 basis, and embryocidal in rabbits given 9 times the MRHD of Lipil on a mg/m2 basis.
Use in lactation: Because of the potential for tumorigenicity as seen in animal studies, Lipil should not be used in women who are breastfeeding. A decision should be made whether to discontinue nursing or to discontinue Lipil.
Use in children: No information is available on the relationship of age to the effects of Lipil in pediatric patients. Safety and efficacy has not been established.
Use in the
Elderly: Clearance of fenofibric acid following a single dose of Lipil in elderly volunteers 77-87 years, was 1.2 L/hr compared to 1.1 L/hr in younger adults, indicating that a similar dosage regimen can be used in the elderly without resulting in an increase in the accumulation of Lipil or its metabolites.
What happens if I miss a dose of Lipil?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.
References
- DailyMed. "FENOFIBRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DrugBank. "fenofibrate". http://www.drugbank.ca/drugs/DB01039 (accessed September 17, 2018).
- MeSH. "Hypolipidemic Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
