Drug Interactions between mipomersen and nintedanib
This report displays the potential drug interactions for the following 2 drugs:
- mipomersen
- nintedanib
Interactions between your drugs
mipomersen nintedanib
Applies to: mipomersen and nintedanib
MONITOR CLOSELY: Coadministration of mipomersen with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Mipomersen can cause elevations in serum transaminases and hepatic steatosis. In a premarketing clinical trial, 12% (4/34) of patients treated with mipomersen had at least one elevation in alanine aminotransferase (ALT) 3 times the upper limit of normal (ULN) or greater, and 9% (3/34) had at least one elevation in ALT 5 times ULN or greater, compared to 0% of the 17 patients treated with placebo. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or partial thromboplastin time (PTT). Mipomersen also increases hepatic fat, with or without concomitant increases in transaminases. In clinical trials of patients with heterozygous familial hypercholesterolemia and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging. The long-term consequences of hepatic steatosis associated with mipomersen therapy are unknown. Hepatic steatosis may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
MANAGEMENT: Caution is advised if mipomersen is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; amiodarone; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; kinase inhibitors; methotrexate; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; tamoxifen; tetracyclines; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; other lipid-lowering medications such as fenofibrate, lomitapide, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Mipomersen has not been studied with other LDL-lowering agents that can also increase hepatic fat, thus concomitant use is not recommended. Patients treated with mipomersen should have serum ALT, AST, alkaline phosphatase, and total bilirubin measured prior to initiation of treatment and regularly during treatment in accordance with the product labeling, and the dosing adjusted or interrupted as necessary. Since alcohol may increase levels of hepatic fat and induce or exacerbate liver injury, the manufacturer recommends that patients taking mipomersen not consume more than one alcoholic drink per day. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.
References (1)
- (2013) "Product Information. Kynamro (mipomersen)." Genzyme Corporation
Drug and food interactions
mipomersen food
Applies to: mipomersen
GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of mipomersen. Mipomersen can cause elevations in serum transaminases and hepatic steatosis. In a premarketing clinical trial, 12% (4/34) of patients treated with mipomersen had at least one elevation in alanine aminotransferase (ALT) 3 times the upper limit of normal (ULN) or greater, and 9% (3/34) had at least one elevation in ALT 5 times ULN or greater, compared to 0% of the 17 patients treated with placebo. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or partial thromboplastin time (PTT). Mipomersen also increases hepatic fat, with or without concomitant increases in transaminases. In clinical trials of patients with heterozygous familial hypercholesterolemia and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging. The long-term consequences of hepatic steatosis associated with mipomersen therapy are unknown. Hepatic steatosis may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
MANAGEMENT: Since alcohol may increase levels of hepatic fat and induce or exacerbate liver injury, the manufacturer recommends that patients taking mipomersen not consume more than one alcoholic drink per day.
References (1)
- (2013) "Product Information. Kynamro (mipomersen)." Genzyme Corporation
nintedanib food
Applies to: nintedanib
ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of nintedanib. After food intake, nintedanib exposure increased by approximately 20% compared to administration under fasted conditions. Absorption was also delayed, as indicated by an increase in the median time to reach maximum plasma concentration (Tmax) from 2 hours in the fasted state to approximately 4 hours under fed conditions, irrespective of the type of food ingested. In an in vitro study, mixing nintedanib capsules with a small amount of apple sauce or chocolate pudding for up to 15 minutes did not have any impact on their pharmaceutical quality, but swelling and deformation of the capsules were observed with longer exposure time due to water uptake of the gelatin capsule shell. Therefore, administration with soft food would not be expected to alter the clinical effect of nintedanib when taken immediately.
GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of nintedanib, which has been shown to be a substrate of the P-glycoprotein (P-gp) efflux transporter and a minor substrate of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of both P-gp-mediated efflux in the gut wall as well as CYP450 3A4-mediated first-pass metabolism in the intestinal tract by certain compounds present in grapefruit.
MANAGEMENT: Nintedanib should be administered with food to reduce the incidence of gastrointestinal effects. Nintedanib capsules may be taken with a small amount (teaspoonful) of cold or room temperature soft food, such as apple sauce or chocolate pudding, and must be swallowed whole (unchewed) immediately, to ensure the capsule stays intact. Food containing grapefruit, grapefruit juice, or Seville oranges should be avoided during treatment with nintedanib.
References (5)
- (2022) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim
- (2021) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (Canada) Ltd
- (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Pty Ltd
- (2023) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Ltd
- (2023) "Product Information. Vargatef (nintedanib)." Boehringer Ingelheim Ltd
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.