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Drug Interactions between ACAM2000 and trabectedin

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

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Interactions between your drugs

Moderate

trabectedin smallpox and monkeypox vaccine

Applies to: trabectedin and ACAM2000 (smallpox and mpox vaccine)

MONITOR: Administration of the smallpox and monkeypox vaccine, which contains a live, attenuated, non-replicating strain of orthopoxvirus, to immunosuppressed patients is generally safe but may be associated with a diminished or suboptimal immunologic response due to antibody inhibition. Such patients may include those who have recently received or are receiving immunosuppressive agents, antilymphocyte globulins, alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids.

MANAGEMENT: It is generally advisable to complete recommended vaccinations, including smallpox and monkeypox vaccine, before starting immunosuppressant or antineoplastic treatment. Clinicians should consult public health authorities and thoroughly assess risks versus benefits prior to administering the smallpox and monkeypox vaccine to immunosuppressed individuals. If the decision is made to vaccinate, titer testing by the Centers for Disease Control and Prevention (CDC) might be considered on a case-by-case basis. Because a correlate of protection has not been established and there is no known antibody titer level that will ensure protection, titer results should be interpreted with caution to avoid providing a false sense of security. Additionally, since immunosuppressed patients might be less likely to mount an effective vaccine response, infections may occur even after full vaccination and outcomes could be particularly severe in these patients, especially following exposure to more virulent orthopoxviruses. Therefore, vaccine recipients might consider avoiding high-risk exposures until after completion of immunosuppressive therapies. Regardless of vaccination status, all individuals who work with orthopoxviruses should wear appropriate personal protective equipment.

References (4)
  1. CDC Centers for Disease Control and Prevention (2019) General Best Practice Guidelines for Immunization: Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf
  2. (2021) "Product Information. Jynneos (smallpox and monkeypox vaccine)." Bavarian Nordic, Inc.
  3. Rao AK, Petersen BW, Whitehill F, et al. (2022) "Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices--United States, 2022 ht"
  4. Anonymous. (2022) Updated ATAGI Clinical Guidance on Vaccination Against MPX (Monkeypox) https://www.health.gov.au/sites/default/files/documents/2022/08/atagi-clinical-guidance-on-vaccination-against-monkeypox.pdf

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

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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