Interactions between Doptelet and Fenofibrate
1 drug interaction and 12 additional warnings found for the following 2 drugs:
- Doptelet (avatrombopag)
- fenofibrate
Drug interactions
Moderate drug interactions
Moderate:
fenofibrate avatrombopag
Applies to: fenofibrate and Doptelet (avatrombopag)
Monitor
Coadministration with fenofibrate may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of CYP450 2C19, 2A6, and 2C9 isoenzymes. The proposed mechanism, based on in vitro data, is decreased clearance due to fenofibrate-mediated inhibition of CYP450 2C19, 2A6, and 2C9.
Management
Until more information is available, caution is advised if fenofibrate is used concomitantly with drugs that are substrates of CYP450 2C19, 2A6, or 2C9 isoenzymes, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever fenofibrate is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.
References (3)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2016) "Product Information. Antara (fenofibrate)." Lupin Pharmaceuticals Inc
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
avatrombopag Food/Lifestyle
Applies to: Doptelet (avatrombopag)
Adjust dosing interval
Food reduces the variability in oral absorption and bioavailability of avatrombopag. According to the product labeling, avatrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) were not affected when administered with either a low-fat (500 calories; 3 g fat, 15 g proteins, 108 g carbohydrates) or high-fat (918 calories; 59 g fat, 39 g proteins, 59 g carbohydrates) meal. However, the variability of avatrombopag exposure was reduced by 40% to 60% with food, and the time to reach Cmax was delayed by 0 to 2 hours relative to the fasted state.
Management
To ensure consistent absorption and plasma drug levels, avatrombopag should be taken with food.
References (1)
- (2018) "Product Information. Doptelet (avatrombopag)." Dova Pharmaceuticals
Disease interactions
11 potential interactions Applies to: 10 conditions, including Anemia, Primary Biliary Cholangitis, Gallbladder Disease, Thrombotic/Thromboembolic Disorder, and Liver Disease.
Anemia
Moderate:
fenofibrate
Fenofibrate has a moderate potential interaction with Anemia.
Mild to moderate hemoglobin, hematocrit and white blood cell decreases have been observed in patients following initiation of fibric acid derivatives therapy. However, these levels stabilize during long-term administration. Thrombocytopenia and agranulocytosis have been reported in individuals treated with these agents. Caution is recommended when treating patients predisposed to hematologic changes. Periodic monitoring of red and white blood cell counts is recommended during the first 12 months of therapy.
Gallbladder Disease
Major:
fenofibrate
Fenofibrate has a major potential interaction with Gallbladder Disease.
The use of fibric acid derivatives is contraindicated in patients with gallbladder disease. A significantly increased incidence of cholelithiasis has been observed in patients treated with the fibric acid derivative, clofibrate, presumably because of increased cholesterol excretion into the bile. Based on two separate studies (the WHO study and the Coronary Drug Project study), clofibrate use was associated with twice the risk of developing cholelithiasis and cholecystitis requiring surgery. Due to their structural and pharmacologic similarities, use of other fibric acid derivatives may be expected to carry the same risk.
History, Thrombotic/Thromboembolic Disorder
Moderate:
Doptelet
The avatrombopag in Doptelet has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.
Thromboembolic complications may result from increases in platelet counts with TPO receptor agonists such as avatrombopag, lusutrombopag, and eltrombopag. Consider the potential for increased risk of thromboembolism when administering these medications to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (Factor V Leiden, Prothrombin 20210 A, Antithrombin deficiency or Protein C or S deficiency).
Liver Disease
Major:
fenofibrate
Fenofibrate has a major potential interaction with Liver Disease.
The use of fibric acid derivatives is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases. Fibric acid derivatives therapy is associated with dose-related hepatotoxicity, including biochemical abnormalities of liver function, hepatitis (hepatocellular, chronic active, as well as cholestatic) and, rarely, cirrhosis. Postmarketing cases of severe drug-induced liver injury, including liver transplantation and death, have been reported. Therapy with these agents should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. Liver function tests, including serum transaminase levels and total bilirubin, should be performed at baseline and periodically throughout the duration of therapy. Therapy should be discontinued if signs or symptoms of liver injury develop or if elevated enzyme levels persist (ALT or AST greater than 3 times the upper limit of normal, or if accompanied by elevation of bilirubin). Do not restart therapy if there is no alternative explanation for the liver injury.
Myoneural Disorder
Major:
fenofibrate
Fenofibrate has a major potential interaction with Myoneural Disorder.
Severe myopathy, including rhabdomyolysis with acute renal failure secondary to myoglobinuria, has been reported rarely with the use of fibric acid derivatives. The myopathy may be dose-related and is characterized by muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with fibric acid derivatives should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. Therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.
Myopathy
Major:
fenofibrate
Fenofibrate has a major potential interaction with Myopathy.
Severe myopathy, including rhabdomyolysis with acute renal failure secondary to myoglobinuria, has been reported rarely with the use of fibric acid derivatives. The myopathy may be dose-related and is characterized by muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with fibric acid derivatives should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. Therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.
Primary Biliary Cholangitis
Major:
fenofibrate
Fenofibrate has a major potential interaction with Primary Biliary Cholangitis.
The use of fibric acid derivatives is contraindicated in patients with primary biliary cirrhosis. These agents may further raise the already elevated cholesterol in these patients.
Protein C Deficiency
Moderate:
Doptelet
The avatrombopag in Doptelet has a moderate potential interaction with Protein C Deficiency.
Thromboembolic complications may result from increases in platelet counts with TPO receptor agonists such as avatrombopag, lusutrombopag, and eltrombopag. Consider the potential for increased risk of thromboembolism when administering these medications to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (Factor V Leiden, Prothrombin 20210 A, Antithrombin deficiency or Protein C or S deficiency).
Renal Dysfunction
Major:
fenofibrate
Fenofibrate has a major potential interaction with Renal Dysfunction.
The use of fibric acid derivatives is contraindicated in patients with significantly impaired renal function. The rate of clearance of fenofibric acid has been shown to decrease substantially when CrCl is below 50 mL/min, with drug accumulation during chronic dosing. Increased adverse effects, including rhabdomyolysis (with or without secondary renal failure) and severe hyperkalemia, have been associated with the use of fibric acid derivatives in patients with renal insufficiency. Therapy with these agents should be administered cautiously in patients with mild or moderate renal impairment. Close clinical monitoring is recommended during therapy.
Moderate:
Doptelet
The avatrombopag in Doptelet has a moderate potential interaction with Renal Dysfunction.
The effect of severe renal impairment (CrCl < 30 mL/min) including patients requiring hemodialysis on avatrombopag pharmacokinetics is unknown. Caution and monitoring is advised.
Thrombotic/Thromboembolic Disorder
Moderate:
Doptelet
The avatrombopag in Doptelet has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.
Thromboembolic complications may result from increases in platelet counts with TPO receptor agonists such as avatrombopag, lusutrombopag, and eltrombopag. Consider the potential for increased risk of thromboembolism when administering these medications to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (Factor V Leiden, Prothrombin 20210 A, Antithrombin deficiency or Protein C or S deficiency).
More resources
Doptelet
A total of 98 drugs are known to interact with Doptelet.
- Doptelet is in the drug class platelet-stimulating agents.
- Doptelet is used to treat the following conditions:
fenofibrate
A total of 147 drugs are known to interact with fenofibrate.
- Fenofibrate is in the drug class fibric acid derivatives.
- Fenofibrate is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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