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Kaletra and Phenytoin injection

Determining the interaction of Kaletra and Phenytoin injection and the possibility of their joint administration.

Check result:

Kaletra <> Phenytoin injection

Relevance: 06.08.2022 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 lopinavir together with phenytoin. Combining these medications may reduce the blood levels of both medications, which may make them less effective in treating your conditions. Contact your doctor if your symptoms worsen or you develop new infections during treatment with these medications. 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. 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:

ADJUST DOSING INTERVAL: Coadministration of lopinavir-ritonavir and phenytoin may result in decreased plasma concentrations of both lopinavir and phenytoin. The proposed mechanism involves phenytoin induction of lopinavir metabolism via CYP450 3A4 and ritonavir induction of phenytoin metabolism via CYP450 2C9 and 2C19. In 12 healthy volunteers, administration of lopinavir-ritonavir (400 mg-100 mg twice daily for 22 days) with phenytoin (300 mg once daily on days 11 thru 22) decreased lopinavir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 24%, 33% and 46%, respectively. Ritonavir Cmax, AUC and Cmin were also reduced by 20%, 28% and 47%, respectively, although only the change in Cmin was statistically significant. In a different arm of the same study, Cmax, AUC and Cmin of phenytoin decreased by 28%, 31% and 34%, respectively, when phenytoin (300 mg once daily for 22 days) was coadministered with lopinavir-ritonavir (400 mg-100 mg twice daily on days 12 thru 22) in 8 healthy subjects.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised if lopinavir-ritonavir is prescribed with phenytoin. Once-daily administration of lopinavir-ritonavir should be avoided when used concomitantly with phenytoin. An increase in the dosage of lopinavir-ritonavir may be necessary, although dosage adjustment has not been evaluated in clinical studies. Close clinical and laboratory monitoring of antiretroviral response is, therefore, recommended. Additionally, the potential for reduced therapeutic effects of phenytoin should be considered during coadministration with lopinavir-ritonavir. Phenytoin serum levels and pharmacologic effects should be closely monitored and the dosage adjusted accordingly.

References

Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."
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Liedtke MD, Lockhart SM, Rathbun RC "Anticonvulsant and antiretroviral interactions." Ann Pharmacother 38 (2004): 482-9
Cerner Multum, Inc. "Australian Product Information." O 0
Brooks J, Daily J, Schwamm L "Protease inhibitors and anticonvulsants." AIDS Clin Care 9 (1997): 87,90
"Product Information. Kaletra (lopinavir-ritonavir)" Abbott Pharmaceutical, Abbott Park, IL.
"Product Information. Dilantin (phenytoin)." Parke-Davis, Morris Plains, NJ.
Barry M, Gibbons S, Back D, Mulcahy F "Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations." Clin Pharmacokinet 32 (1997): 194-209
Sommadossi JP "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS 13 (1999): s29-40
Department of Health and Human Services "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available from: URL: https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultAndAdolescentGL.pdf." ([2015, April 8]):
Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids 14 (2000): 1333-9
Lim ML, Min SS, Eron JJ, et al "Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction." J Acquir Immune Defic Syndr 36 (2004): 1034-40

Kaletra

Generic Name: lopinavir / ritonavir

Brand name: Kaletra

Synonyms: n.a.

What is Kaletra?

Phenytoin injection

Generic Name: phenytoin

Brand name: Dilantin, Phenytek, Dilantin Infatabs, Phenytoin Sodium, Prompt

Synonyms: Phenytoin

What is Phenytoin injection?

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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.

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