About us Contacts Drug interactions: 390 212
Drug search by name

PCE Dispertab and Vinorelbine Intravenous

Determining the interaction of PCE Dispertab and Vinorelbine Intravenous and the possibility of their joint administration.

Check result:
PCE Dispertab <> Vinorelbine Intravenous
Relevance: 03.12.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Talk to your doctor before using vinorelbine together with erythromycin. Combining these medications may significantly increase the blood levels and effects of vinorelbine. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. You should seek medical attention if you experience increased side effects of vinorelbine such as constipation, abdominal pain or bloating, difficulty urinating, numbness or tingling in hands and feet, muscle weakness, difficulty walking, hearing loss, seizures, unusual or excessive bleeding, easy bruising, paleness, fatigue, fainting, infection, fever, chills, sore throat, or other flu-like symptoms. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 and/or P-glycoprotein may significantly increase the plasma concentrations of vinca alkaloids, which are substrates of both the hepatic microsomal isoenzyme and intracellular efflux transporter. Although pharmacokinetic data are not available, the interaction has been associated with severe and life-threatening toxicities in both adult and pediatric cancer patients. Paralytic ileus, intestinal obstruction and perforation, laryngeal nerve paresis requiring mechanical ventilation, neurogenic bladder, paresthesia, paralysis, hypotension, hypertension, heart failure, hyponatremia secondary to SIADH, seizures, profound myelosuppression, and septic shock have been reported. Most cases have involved vincristine or vinblastine in combination with itraconazole. However, the interaction has also been reported with other known potent inhibitors such as clarithromycin, erythromycin, cyclosporine, posaconazole, voriconazole and ritonavir, as well as less potent ones such as nifedipine and isoniazid. In adults with acute lymphoblastic leukemia receiving vincristine as part of their chemotherapeutic regimen, neurotoxicity (paresthesia, muscle weakness, and paralytic ileus) was more severe and occurred earlier and more frequently in 14 patients coadministered itraconazole 400 mg/day for antifungal prophylaxis than in 460 previous patients who did not receive itraconazole (29% vs. 6%). Similarly, in a retrospective cohort study consisting of 25 patients receiving 59 courses of vinorelbine-containing chemotherapy, the incidence of grade 3 or 4 neutropenia was 63.2% in patients who were coadministered clarithromycin, compared to 27.5% in those who did not receive clarithromycin. The incidence of grade 4 neutropenia was also higher in the clarithromycin group, 31.6% vs. 2.5%. Four patients who had received vinorelbine both with and without clarithromycin had lower neutrophil counts during clarithromycin coadministration. A retrospective study to assess vincristine dosing and toxicity in combination with azoles found that vincristine dosing modifications (i.e., dose reductions, dose delays, therapy discontinuation) occurred in 58.6% of patients who received concomitant azole therapy (n=29) compared to 23.8% of patients who did not (n=21). The mean dose reduction of vincristine when combined with an azole was 46.5%. Symptoms of decreased peristalsis were also more common in the azole group, 65.5% vs. 28.6%. The individual incidence was 50%, 75%, and 66.6% in patients receiving fluconazole, voriconazole, and posaconazole, respectively. In addition, patients in the azole group were more likely to have an incomplete course of vincristine, 48.3% vs. 9.5%. Most reported cases of toxicity have been reversible following discontinuation of the CYP450 3A4 inhibitor, and many of the patients tolerated their chemotherapy in the absence of the inhibitor or after dose adjustment. In one incident, however, a patient who had been on itraconazole for fungal pneumonia developed constipation, mucositis, and granulocytopenia within one week after the first dose of vinorelbine and cisplatin, and died 12 days later. No other details were available.

MANAGEMENT: Concomitant use of vinca alkaloids with potent CYP450 3A4 and/or P-glycoprotein inhibitors should be avoided if possible. Otherwise, conservative dosing of the antineoplastic should be considered, and the patient closely monitored for toxicity. Based on the known half-life of vinca alkaloids (24 to 48 hours), the time course of interaction is expected to be approximately 5 to 7 days. Patients should be advised to seek medical attention if they experience symptoms that could indicate neuro- or myelotoxicity, including constipation, abdominal pain or bloating, urinary retention, paresthesia, paralysis, muscle weakness, hearing loss, seizures, erratic blood pressure changes, unusual or excessive bleeding, easy bruising, pallor, fatigue, dizziness, lightheadedness, fever, chills, and sore throat. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the antineoplastic dosage is adjusted upward to the previous dosage.

References
  • Bermudez M, Fuster JL, Llinares E, Galera A, Gonzalez C "Itraconazole-related increased vincristine neurotoxicity: case report and review of literature." J Pediatr Hematol Oncol 27 (2005): 389-392
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • Gillies J, Hung KA, Fitzsimons E, Soutar R "Severe vincristine toxicity in combination with itraconazole." Clin Lab Haematol 20 (1998): 123-4
  • Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201
  • Cerner Multum, Inc. "Australian Product Information." O 0
  • Harnicar S, Adel N, Jurcic J "Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients." J Oncol Pharm Pract 15 (2009): 175-82
  • Jain S, Kapoor G "Severe life threatening neurotoxicity in a child with acute lymphoblastic leukemia receiving posaconazole and vincristine." Pediatr Blood Cancer 54 (2010): 783
  • "Product Information. Velban (vinblastine)." Lilly, Eli and Company, Indianapolis, IN.
  • Fedeli L, Colozza M, Boschetti E, et al. "Pharmacokinetics of vincristine in cancer patients treated with nifedipine." Cancer 64 (1989): 1805-11
  • Antoniou T, Tseng AL "Interactions between antiretrovirals and antineoplastic drug therapy." Clin Pharmacokinet 44 (2005): 111-145
  • Murphy JA, Ross LM, Gibson BE "Vincristine toxicity in five children with acute lymphoblastic leukaemia." Lancet 346 (1995): 443
  • Tobe SW, Siu LL, Jamal SA, Skorecki KL, Murphy GF, Warner E "Vinblastine and erythromycin: an unrecognized serious drug interaction." Cancer Chemother Pharmacol 35 (1995): 188-90
  • van Schie RM, Bruggemann RJ, Hoogerbrugge PM, Te Loo DM "Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia." J Antimicrob Chemother 66 (2011): 1853-6
  • Porter CC, Carver AE, Albano EA "Vincristine induced peripheral neuropathy potentiated by voriconazole in a patient with previously undiagnosed CMT1X." Pediatr Blood Cancer 52 (2009): 298-300
  • Leveque D, Santucci R, Pavillet J, Herbrecht R, Bergerat JP "Paralytic ileus possibly associated with interaction between ritonavir/lopinavir and vincristine." Pharm World Sci 31 (2009): 619-21
  • Kamaluddin M, McNally P, Breatnach F, et al "Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies." Acta Paediatr 90 (2001): 1204-7
  • Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."
  • Kajita J, Kuwabara T, Kobayashi H, Kobayashi S "CYP3A4 is mainly responsibile for the metabolism of a new vinca alkaloid, vinorelbine, in human liver microsomes." Drug Metab Dispos 28 (2000): 1121-7
  • Bosque E "Possible drug interaction between itraconazole and vinorelbine tartrate leading to death after one dose of chemotherapy." Ann Intern Med 134 (2001): 427
  • "Product Information. Oncovin (vincristine)." Lilly, Eli and Company, Indianapolis, IN.
  • Jeng MR, Feusner J "Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia." Pediatr Hematol Oncol 18 (2001): 137-42
  • Corona G, Vaccher E, Spina M, Toffoli G "Potential hazard drug-drug interaction between boosted protease inhibitors and vinblastine in HIV patients with Hodgkin's lymphoma." AIDS 27 (2013): 1033-5
  • Eiden C, Palenzuela G, Hillaire-Buys D, et al. "Posaconazole-increased vincristine neurotoxicity in a child: a case report." J Pediatr Hematol Oncol 31 (2009): 292-5
  • Sathiapalan RK, El-Solh H "Enhanced vincristine neurotoxicity from drug interactions: case report and review of literature." Pediatr Hematol Oncol 18 (2001): 543-6
  • Takahashi N, Kameoka Y, Yamanaka Y, et al. "Itraconazole oral solution enhanced vincristine neurotoxicity in five patients with malignant lymphoma." Intern Med 47 (2008): 651-3
  • Bashir H, Motl S, Metzger ML, et al. "Itraconazole-enhanced chemotherapy toxicity in a patient with Hodgkin lymphoma." J Pediatr Hematol Oncol 28 (2006): 33-35
  • Moriyama B, Falade-Nwulia O, Leung J, et al. "Prolonged half-life of voriconazole in a CYP2C19 homozygous poor metabolizer receiving vincristine chemotherapy: avoiding a serious adverse drug interaction." Mycoses 54 (2011): e877-9
  • Chan JD "Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports." Pharmacotherapy 18 (1998): 1304-7
  • Bohme A, Ganser A, Hoelzer D "Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL." Ann Hematol 71 (1995): 311-2
  • Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R "Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions." Biochem Pharmacol 45 (1993): 853-61
  • Sathiapalan RK, Al-Nasser A, El-Solh H, Al-Mohsen I, Al-Jumaah S "Vincristine-itraconazole interaction: cause for increasing concern." J Pediatr Hematol Oncol 24 (2002): 591
  • Chen S, Wu D, Sun A, et al "Itraconazole-enhanced vindesine neurotoxicity in adult acute lymphoblastic leukaemia." Am J Hematol 82 (2007): 942
  • Kivisto KT, Kroemer HK, Eichelbaum M "The role of human cytochrome p450 enzymes in the metabolism of anticancer agents: implications for drug interactions." Br J Clin Pharmacol 40 (1995): 523-30
  • Haddad A, Davis M, Lagman R "The pharmacological importance of cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for avoiding adverse drug interactions." Support Care Cancer 15 (2007): 251-7
  • Zhou-Pan XR, Seree E, Zhou XJ, et al "Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions." Cancer Res 53 (1993): 5121-6
  • Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y "Potentiation of vincristine and adriamycin effects in human hemopoietic tumor cell lines by calcium antagonists and calmodulin inhibitors." Cancer Res 43 (1983): 2267-72
  • Ariffin H, Omar KZ, Ang EL, Shekhar K "Severe vincristine neurotoxicity with concomitant use of itraconazole." J Paediatr Child Health 39 (2003): 638-9
  • Mantadakis E, Amoiridis G, Kondi A, Kalmanti M "Possible increase of the neurotoxicity of vincristine by the concurrent use of posaconazole in a young adult with leukemia." J Pediatr Hematol Oncol 29 (2007): 130
  • Kotb R, Vincent I, Dulioust A, et al. "Life-threatening interaction between antiretroviral therapy and vinblastine in HIV-associated multicentric Castleman's disease." Eur J Haematol 76 (2006): 269-71
  • Yano R, Tani D, Watanabe K, et al. "Evaluation of potential interaction between vinorelbine and clarithromycin." Ann Pharmacother 43 (2009): 453-8
PCE Dispertab

Generic Name: erythromycin

Brand name: EES. Granules, EES-400 Filmtab, EryPed 200, EryPed 400, Ery-Tab, Erythrocin Lactobionate, Erythrocin Stearate Filmtab, PCE Dispertab, E. E. S, EryPed, Erythrocin, Erythromycin Filmtabs, Erythromycin Lactobionate - IV

Synonyms: PCE Dispertab (Oral), PCE, PCE (Oral)

Vinorelbine Intravenous

Generic Name: vinorelbine

Brand name: Navelbine

Synonyms: Vinorelbine

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle