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Drug Interactions between Adcetris and Esbriet

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

brentuximab vedotin pirfenidone

Applies to: Adcetris (brentuximab) and Esbriet (pirfenidone)

MONITOR: Coadministration of brentuximab vedotin with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with brentuximab vedotin. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and typically occurred after the first dose or after a rechallenge. Preexisting liver disease and elevated baseline liver enzymes may also increase the risk.

MANAGEMENT: The risk of hepatic injury should be considered when brentuximab vedotin is used with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). 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. Liver enzymes and bilirubin should be measured before and during treatment, especially in patients with underlying hepatic disease or marked baseline transaminase elevations. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dosage, or discontinuation of brentuximab vedotin in accordance with the product labeling.

References (1)
  1. (2011) "Product Information. Adcetris (brentuximab vedotin)." Seattle Genetics Inc

Drug and food interactions

Moderate

pirfenidone food

Applies to: Esbriet (pirfenidone)

ADJUST DOSING INTERVAL: Food significantly slows the rate but only modestly reduces the extent of absorption of pirfenidone. In healthy, older adult volunteers aged 50 to 66 years, administration of a single 801 mg oral dose of pirfenidone in the fed state resulted in an approximately 50% reduction in peak plasma concentration (Cmax) and a 15% to 20% reduction in systemic exposure (AUC) compared to administration in the fasted state. Median time to reach peak concentration (Tmax) increased from 0.5 hours to 3 hours with food. Less nausea and dizziness were observed in fed subjects compared to fasted subjects.

GENERALLY AVOID: Consumption of grapefruit juice is associated with inhibition of CYP450 1A2 and may increase the plasma concentrations of pirfenidone, which is primarily metabolized by the isoenzyme.

GENERALLY AVOID: Cigarette smoking may reduce pirfenidone exposure due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of pirfenidone. Following a single 801 mg oral dose of pirfenidone in 25 smokers and 25 healthy nonsmokers, the Cmax and AUC of pirfenidone in smokers were 68% and 46% of those in nonsmokers, respectively.

MANAGEMENT: Pirfenidone should be administered with food to reduce the likelihood of dizziness and gastrointestinal side effects such as nausea, diarrhea, dyspepsia, and vomiting. Patients who experience intolerance to therapy due to these adverse events should be reminded to take pirfenidone with food. If symptoms do not improve, or they worsen in severity, a dosage reduction or discontinuation of therapy may be warranted. Patients should be advised to avoid consumption of grapefruit and grapefruit juice during treatment with pirfenidone. Cigarette smoking should also be avoided during therapy to prevent reduced exposure to pirfenidone.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Esbriet (pirfenidone)." Intermune Inc

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

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

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