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Drug Interactions between trabectedin and Xgeva

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

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Interactions between your drugs

Moderate

trabectedin denosumab

Applies to: trabectedin and Xgeva (denosumab)

MONITOR: Concomitant use of immunosuppressive or myelosuppressive agents with denosumab may increase the risk of serious infections. Denosumab binds to and inhibits the receptor activator of nuclear factor kappa-B ligand (RANKL), which is expressed on activated T and B lymphocytes and in lymph nodes. Thus, denosumab alone may increase the risk of infections. In a clinical trial of over 7800 women with postmenopausal osteoporosis, the incidence of nonfatal serious infections was 3.3% in the placebo group and 4.0% in the denosumab group. Specifically, hospitalizations due to skin infections including erysipelas and cellulitis (<0.1% placebo vs. 0.4% denosumab) and serious infections in the abdomen (0.7% placebo vs. 0.9% denosumab), urinary tract (0.5% placebo vs. 0.7% denosumab), and ear (0.0% placebo vs. 0.1% denosumab) were reported. Endocarditis was reported in no placebo patients and 3 denosumab-treated patients. There was no difference in the incidence of opportunistic infections or infections resulting in death between the placebo and denosumab groups. The overall incidence of infections was also similar between the two groups.

MANAGEMENT: Caution is advised if denosumab must be used in combination with immuno- or myelosuppressive agents. Patients should be advised to contact their physician if they develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. The need for continued denosumab therapy should be assessed when serious infections occur during treatment.

References

  1. (2010) "Product Information. Prolia (denosumab)." Amgen USA

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Drug and food interactions

Moderate

trabectedin food

Applies to: trabectedin

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of trabectedin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

GENERALLY AVOID: Coadministration of trabectedin with other agents known to induce hepatotoxicity such as alcohol may potentiate the risk of liver injury. Reversible, acute increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have occurred frequently in patients treated with trabectedin alone or with pegylated liposomal doxorubicin in clinical trials. In one U.S. trial with 378 patients, grade 3 or 4 elevated liver function tests (defined as elevations in ALT, AST, total bilirubin, or alkaline phosphatase) were reported in 35% of patients receiving trabectedin. ALT or AST elevations greater than eight times the upper limit of normal (ULN) occurred in 18% of patients, and drug-induced liver injury (defined as concurrent elevations in ALT or AST more than three times ULN, alkaline phosphatase less than two times ULN, and total bilirubin at least two times ULN) occurred in 1.3% of patients.

MANAGEMENT: Consumption of grapefruit or grapefruit juice during treatment with trabectedin should be avoided. Excessive use of alcohol is also not recommended. 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. Monitoring of alkaline phosphatase, bilirubin, AST, and ALT should occur regularly during trabectedin treatment in accordance with the product labeling, or as often as necessary when clinical symptoms develop. Trabectedin must not be used in patients with elevated bilirubin at the time of initiation of cycle. Elevated liver function tests should be managed with treatment interruption, dosage reduction, or permanent discontinuation depending on the severity and duration of abnormality.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2010) "Product Information. Yondelis (trabectedin)." Janssen Pharmaceuticals

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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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