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PCE Dispertab and Tretinoin

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

Check result:
PCE Dispertab <> Tretinoin
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:

Erythromycin may increase the blood levels of tretinoin. You may be more likely to experience side effects, including a rare but potentially serious condition called pseudotumor cerebri that is associated with elevated pressure in the brain. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor immediately if you develop signs and symptoms of pseudotumor cerebri such as headache, nausea, vomiting, visual disturbances, light sensitivity, or ringing in the ears. 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:

MONITOR: Coadministration with potent inhibitors of CYP450 2C8, 2C9, and/or 3A4 may increase the plasma concentrations and toxicities of tretinoin, which is a substrate of these isoenzymes. There have been isolated reports of pseudotumour cerebri, hypercalcemia, and acute renal failure in patients receiving tretinoin with fluconazole, itraconazole or voriconazole, all of which are considered potent inhibitors of at least one CYP450 isoenzyme involved in the metabolism of tretinoin. The conditions resolved following interruption of tretinoin therapy and/or discontinuation of the azole antifungal agent. As tretinoin is thought to undergo autoinduction of its own metabolism, CYP450 inhibitors have been investigated for use to boost plasma tretinoin concentrations and to overcome treatment resistance that often occurs with continued tretinoin therapy. In a study of two patients with acute promyelocytic leukemia, tretinoin systemic exposure (AUC) was found to be reduced significantly from baseline after one week of treatment. Following two daily doses of fluconazole administered 1 hour before tretinoin, the AUC of tretinoin increased by about 2- to 4-fold compared to day eight of tretinoin treatment alone, but similar to AUCs reported at baseline. In 13 patients who had received tretinoin daily for 4 consecutive weeks, administration of ketoconazole (400 to 1200 mg oral dose) 1 hour before the tretinoin dose on day 29 led to a 72% increase in tretinoin mean plasma AUC. Likewise, in 6 patients with lung cancer, a single 400 mg dose of ketoconazole (but not a 200 mg dose) one hour before tretinoin on day 29 increased tretinoin AUC by 115% compared to day 28 when tretinoin was given alone. No effect was observed when ketoconazole was given on day 2 relative to tretinoin alone on day one. By contrast, one study showed that prolonged ketoconazole administration (400 mg initially, then 200 mg daily for 14 days) in patients receiving tretinoin (45 mg/m2 twice daily for 14 days) had no effect on tretinoin auto-induction, but was associated with more vomiting.

MANAGEMENT: Caution is advised when tretinoin is prescribed in combination with potent inhibitors of CYP450 2C8, 2C9, and/or 3A4. Patients should be closely monitored and advised to seek medical attention immediately if they develop early symptoms of pseudotumour cerebri such as headache, nausea, vomiting, visual disturbances, photosensitivity, and tinnitus.

References
  • Cordoba R, Ramirez E, Lei SH, et al. "Hypercalcemia due to an interaction of all-trans retinoic acid (ATRA) and itraconazole therapy for acute promyelocytic leukemia successfully treated with zoledronic acid." Eur J Clin Pharmacol 64 (2008): 1031-2
  • Adamson PC "Pharmacokinetics of all-trans-retinoic acid: clinical implications in acute promyelocytic leukemia." Semin Hematol 31 (1994): 14-7
  • Hameed DA, el-Metwally TH "The effectiveness of retinoic acid treatment in bladder cancer: impact on recurrence, survival and TGFalpha and VEGF as end-point biomarkers." Cancer Biol Ther 7 (2008): 92-100
  • Lotan Y, Lotan R "Prevention of bladder cancer recurrence by retinoic acid-ketoconazole: a promising strategy?" Cancer Biol Ther 7 (2008): 101-2
  • "Product Information. Vesanoid (tretinoin)." Roche Laboratories, Nutley, NJ.
  • Dixon KS, Hassoun A "Pseudotumor cerebri due to the potentiation of all-trans retinoic acid by voriconazole." J Am Pharm Assoc (2003) 50 (2010): 742-4
  • Muindi JRF, Young CW, Warrell RP "Clinical pharmacology of all-trans retinoic acid." Leukemia 8 (1994): 1807-12
  • Kizaki M, Ueno H, Yamazoe Y, et al "Mechanisms of retinoid resistance in leukemic cells: possible role of cytochrome P450 and P-glycoprotein." Blood 87 (1996): 725-33
  • Rigas JR, Francis PA, Muindi JR, Kris MG, Huselton C, DeGrazia F, Orazem JP, Young CW, Warrell RP Jr "Constitutive variability in the pharmacokinetics of the natural retinoid, all-trans-retinoic acid, and its modulation by ketoconazole." J Natl Cancer Inst 85 (1993): 1921-6
  • Moresco G, Martinello F, Souza LC "[Acute renal failure in patient treated with ATRA and amphotericin B: case report]." J Bras Nefrol 33 (2011): 276-81
  • Marill J, Cresteil T, Lanotte M, Chabot GG "Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites." Mol Pharmacol 58 (2000): 1341-8
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)

Tretinoin

Generic Name: tretinoin

Brand name: Vesanoid

Synonyms: Tretinoin (Systemic)

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
Disease interaction