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Drug Interactions between samarium sm 153 lexidronam and trabectedin

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

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Interactions between your drugs

Major

samarium sm 153 lexidronam trabectedin

Applies to: samarium sm 153 lexidronam and trabectedin

GENERALLY AVOID: Theoretical concerns exist that chemotherapeutic agents and other bone marrow depressants may potentiate the myelosuppressive effects of samarium sm 153 lexidronam. In clinical trials, white blood cell and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 95% of patients within three to five weeks after administration of samarium sm 153 lexidronam, and tended to return to pretreatment levels by eight weeks. The potential for additive bone marrow toxicity with myelotoxic treatments including chemotherapy or external beam radiation has not been studied.

MANAGEMENT: The manufacturer recommends avoiding concomitant use of samarium sm 153 lexidronam with chemotherapy or external beam radiation therapy unless benefits are anticipated to outweigh the risks. Moreover, samarium sm 153 lexidronam should not be given after either of these treatments until there has been time for adequate marrow recovery. Caution and close monitoring of bone marrow function are advisable if coadministration with other myelotoxic agents is required. Patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, unusual bleeding or bruising, or signs 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.

References

  1. (2001) "Product Information. Quadramet (samarium sm 153 lexidronam)." Berlex Laboratories
  2. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid

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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.

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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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