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Drug Interactions between Onxol and RabAvert

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

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Interactions between your drugs

Moderate

PACLitaxel rabies vaccine, purified chick embryo cell

Applies to: Onxol (paclitaxel) and RabAvert (rabies vaccine, purified chick embryo cell)

MONITOR: The administration of inactivated, killed, or otherwise noninfectious vaccines 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: In general, the U.S. Department of Public Health Advisory Committee on Immunization Practices (ACIP) recommends that inactivated or killed vaccines be administered to non-HIV immunosuppressed patients according to the same guidelines as for healthy patients. However, higher dosages, more frequent boosters, and/or serological testing may be required in some cases. Local guidelines and prescribing information for individual vaccines should be consulted. For Haemophilus influenzae b vaccine, some experts recommend that it be administered at least 2 weeks before starting or 3 months after discontinuing chemotherapy when used in patients with Hodgkin's disease. For rabies vaccine, some authorities suggest that immunosuppressive agents should generally be avoided during postexposure therapy except when absolutely necessary for the treatment of other conditions. For SARS-CoV-2 (COVID-19) vaccines, vaccination should generally be completed at least 2 weeks before initiation or resumption of immunosuppressive therapies; however, decisions to delay or temporarily withhold immunosuppressive therapy to complete COVID-19 vaccination should consider the individual's risks relative to their underlying condition. Some authorities recommend administering the COVID-19 vaccine approximately 4 weeks prior to the next scheduled therapy for those on B-cell-depleting therapies on a continuing basis. Additional shots, boosters, and even revaccination may be appropriate depending on age, prior COVID-19 vaccine formulation(s) received, current or planned immunosuppressive therapy, and other factors in individuals with moderate to severe immune compromise due to medical conditions or immunosuppressive medications or treatments (e.g., solid organ transplant recipients on immunosuppressive therapy; patients on active treatment for solid tumor and hematologic malignancies). Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

References

  1. "Product Information. Fluzone (influenza virus vaccine, inactivated)." Connaught Laboratories Inc
  2. "Product Information. Omnihib (haemophilus b conjugate vaccine (obsolete))." SmithKline Beecham PROD
  3. "Product Information. Havrix (HepA) (hepatitis A adult vaccine)." SmithKline Beecham PROD
  4. CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18
  5. "Product Information. Imovax Rabies (rabies vaccine, human diploid cell)." sanofi pasteur (2022):
  6. "Product Information. Biothrax (anthrax vaccine adsorbed)." Emergent BioSolutions Inc. (2003):
  7. Cerner Multum, Inc. "Australian Product Information." O 0
  8. "Product Information. Influenza Virus Vaccine, H5N1, Inactivated (influenza virus vaccine, H5N1, inactivated)." GlaxoSmithKline (2022):
  9. CDC Centers for Disease Control and Prevention "General Best Practice Guidelines for Immunization: Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf" (2019):
  10. Department of Health. National Health Service "Immunisation Against Infectious Disease - "The Green Book". Chapter 6: Contraindications and special considerations. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/Greenbook_chapter_6.pdf" (2019):
  11. CDC Centers for Disease Control and Prevention "Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html" (2022):
  12. Centers for Disease Control and Prevention "Use of COVID-19 vaccines in the U.S. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html" (2023):
  13. UK Health Security Agency "COVID-19: the green book, chapter 14a https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a" (2023):
  14. Public Health Agency of Canada "Immunization of immunocompromised persons: Canadian immunization guide https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3-vaccination-specific-populations/page-8-immunization-immunocompromised-p" (2023):
  15. Public Health Agency of Canada "COVID-19 vaccines: Canadian immunization guide. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-26-covid-19-vaccine.html" (2023):
  16. Australian Government. Department of Health and Aged Care "Australian immunisation handbook: COVID-19. https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/covid-19" (2023):
View all 16 references

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Drug and food interactions

Moderate

PACLitaxel food

Applies to: Onxol (paclitaxel)

MONITOR: Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may increase the plasma concentrations of paclitaxel, which is a substrate of the isoenzyme. Current data suggest that consumption of large quantities of grapefruit juice inhibit both intestinal and hepatic CYP450 3A4 due to certain compounds present in grapefruit. Specific data for paclitaxel are lacking; however, in a case report of a 52-year-old woman with esophageal squamous cell carcinoma receiving a twice weekly chemotherapy regimen including intravenous docetaxel (40 mg/m2) reported that docetaxel systemic exposure (AUC) increased by 65% compared with the AUC target of 1.96 mg*h/L and clearance decreased by 63%, with a 71% reduction in the patient's neutrophil count. In the absence of other CYP450 3A4 inhibitors, these effects were attributed to daily consumption of 250 mL of grapefruit juice, which the patient had been consuming for at least 3 months. Two weeks after the patient ceased the grapefruit juice, the docetaxel AUC was closer to the target value and the neutrophil count reduction was less than 35%. In addition, in a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel AUC increased by 2.2-fold and clearance decreased by 49% when intravenous docetaxel was given at a reduced dosage of 10 mg/m2 in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally once daily for 3 days) compared to docetaxel administered alone at 100 mg/m2.

MANAGEMENT: Caution is recommended if paclitaxel is to be used in combination with grapefruit and grapefruit juice. Patients should be closely monitored for the development of paclitaxel toxicity, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy and dose adjustment considered per local treatment protocols.

References

  1. "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer PROD (2001):
  2. Aronson JK, Grahame-Smith DG "Clinical pharmacology: adverse drug interactions." Br Med J 282 (1981): 288-91
  3. McInnes GT, Brodie MJ "Drug interactions that matter: a critical reappraisal." Drugs 36 (1988): 83-110
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Yong WP, Wang LZ, Tham LS, et al. "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol 62 (2008): 243-51
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther 5 (2006): 833-9
  8. Valenzuela B, Rebollo J, Perez T, Brugarolas A, Perez-Ruixo JJ "Effect of grapefruit juice on the pharmacokinetics of docetaxel in cancer patients: a case report." Br J Clin Pharmacol (2011):
  9. Starr SP, Hammann F, Gotta V, et al. "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol 450 (2016): 22-27
View all 9 references

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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.