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Drug Interactions between thalidomide and trabectedin

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

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Interactions between your drugs

Moderate

thalidomide trabectedin

Applies to: thalidomide and trabectedin

MONITOR: Thalidomide can cause peripheral neuropathy, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Peripheral neuropathy is a common, potentially severe side effect of thalidomide that may be irreversible. The condition generally occurs following chronic use over a period of months, although there have also been reported cases following relatively short-term use. The median time to first neuropathy event was 42.3 weeks in one phase 3 study. Occasionally, symptoms may occur some time after thalidomide treatment has been discontinued. The incidence of neuropathy requiring thalidomide discontinuation, dosage reduction, or interruption increases with cumulative dose and duration of therapy.

MANAGEMENT: Caution is advised if thalidomide is used in combination with other neurotoxic agents. All patients treated with thalidomide should be examined at monthly intervals for the first three months of therapy and periodically thereafter to detect early signs of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Electrophysiological testing may be performed at baseline and every six months during therapy to detect asymptomatic neuropathy. Consideration should be given to immediate discontinuation of thalidomide in patients who develop peripheral neuropathy to limit further damage. Symptoms may improve or return to baseline in some patients upon discontinuation of thalidomide, although the complete time course of this toxicity has not been fully characterized. If necessary, therapy should generally be reinstituted only after neuropathy returns to baseline status. A dosage reduction of thalidomide may be required as clinically indicated.

References

  1. "Product Information. Thalomid (thalidomide)." Celgene Corporation PROD (2001):
  2. Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

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Drug and food interactions

Moderate

thalidomide food

Applies to: thalidomide

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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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." O 0
  2. "Product Information. Yondelis (trabectedin)." Janssen Pharmaceuticals (2010):

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.