What happens if I overdose Gadolip 45?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of Gadolip 45 capsules:
Store Gadolip 45 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 Gadolip 45 capsules out of the reach of children and away from pets.
Overdose of Gadolip 45 in details
Only anecdotal cases of Gadolip 45 overdosage have been reported. In the majority of cases, no overdose symptoms were reported.
There is no specific treatment for overdose with Gadolip 45. 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 Gadolip 45 is highly bound to plasma proteins, hemodialysis should not be considered.
What should I avoid while taking Gadolip 45?
If you also take cholestyramine, colesevelam, or colestipol: Wait 4 to 6 hours after taking any of these other medicines before you take Gadolip 45. Avoid taking Gadolip 45 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 Gadolip 45.
Gadolip 45 warnings
Mortality and Coronary Heart Disease Morbidity
The effect of Gadolip 45 on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established. Because of similarities between Gadolip 45 and Gadolip 45, clofibrate, and gemfibrozil, the findings in the following large randomized, placebo-controlled clinical studies with these fibrate drugs may also apply to Gadolip 45.
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 Gadolip 45. The mean duration of follow-up was 4.7 years. Gadolip 45 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 Gadolip 45 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 Gadolip 45. Gadolip 45 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 Gadolip 45 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 Gadolip 45 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 Gadolip 45 with colchicine.
Liver Function
Gadolip 45 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 Gadolip 45, 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 Gadolip 45 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 Gadolip 45, increases to > 3 times the upper limit of normal in ALT occurred in 5.3% of patients taking Gadolip 45 versus 1.1% of patients treated with placebo. The incidence of increases in transaminases observed with Gadolip 45 therapy may be dose related. In an 8-week dose-ranging study of Gadolip 45 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 Gadolip 45 once daily and was 0% in those receiving dosages equivalent to 45 mg Gadolip 45 once daily or less, or placebo. Hepatocellular, chronic active, and cholestatic hepatitis observed with Gadolip 45 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 Gadolip 45, 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 Gadolip 45 as well as patients receiving Gadolip 45. In the pooled analysis of three 12-week, double-blind, controlled studies of Gadolip 45, increases in creatinine to > 2 mg/dL occurred in 0.8% of patients treated with Gadolip 45 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 Gadolip 45 is suggested. Renal monitoring should be considered for patients at risk for renal insufficiency, such as the elderly and those with diabetes.
Cholelithiasis
Gadolip 45, like Gadolip 45, clofibrate, and gemfibrozil, may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Gadolip 45 therapy should be discontinued if gallstones are found.
Coumarin Anticoagulants
Caution should be exercised when Gadolip 45 is given in conjunction with oral coumarin anticoagulants. Gadolip 45 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 Gadolip 45. 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 Gadolip 45 and Gadolip 45 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 Gadolip 45 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 Gadolip 45- 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 Gadolip 45 group. For DVT, there were 48 events (1%) in the placebo group and 67 (1%) in the Gadolip 45 group (p = 0.074); and for PE, there were 32 (0.7%) events in the placebo group and 53 (1%) in the Gadolip 45 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 Gadolip 45?
Some medical conditions may interact with CIP - Gadolip 45. 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 - Gadolip 45. 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 - Gadolip 45'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 - Gadolip 45
This may not be a complete list of all interactions that may occur. Ask your health care provider if CIP - Gadolip 45 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.
Gadolip 45 precautions
Cross-Sensitivity and/or Related Problems: Gadolip 45 has chemical, pharmacological and clinical similarities to other fibrate agents, clofibrate and gemfibrozil.
Carcinogenicity: A 24-month study in rats given Gadolip 45 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: Gadolip 45 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. Gadolip 45 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Gadolip 45 has been shown to be embryocidal and teratogenic in rats given 7-10 times the maximum recommended human dose (MRHD) of Gadolip 45 on mg/m2 basis, and embryocidal in rabbits given 9 times the MRHD of Gadolip 45 on a mg/m2 basis.
Use in lactation: Because of the potential for tumorigenicity as seen in animal studies, Gadolip 45 should not be used in women who are breastfeeding. A decision should be made whether to discontinue nursing or to discontinue Gadolip 45.
Use in children: No information is available on the relationship of age to the effects of Gadolip 45 in pediatric patients. Safety and efficacy has not been established.
Use in the
Elderly: Clearance of fenofibric acid following a single dose of Gadolip 45 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 Gadolip 45 or its metabolites.
What happens if I miss a dose of Gadolip 45?
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
