Skip to main content
SpringerLink
Log in

A Review of Pharmacokinetic Drug–Drug Interactions with the Anthelmintic Medications Albendazole and Mebendazole

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (C max) of mebendazole; dexamethasone increased the area under the plasma concentration–time curve (AUC) of albendazole; levamisole decreased the C max of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. World Health Organization. WHO|Control of neglected tropical diseases is feasible. World Health Organization. Available at: http://www.who.int/neglected_diseases/en/. Accessed 25 Mar 2014.

  2. Molyneux DH, Bradley M, Hoerauf A, Kyelem D, Taylor MJ. Mass drug treatment for lymphatic filariasis and onchocerciasis. Trends Parasitol. 2003;19:516–22.

    Article  CAS  PubMed  Google Scholar 

  3. Centers for Disease Control and Prevention. Neglected tropical diseases. Available at: http://www.cdc.gov/globalhealth/ntd/diseases/index.html. Accessed 28 Dec 2014.

  4. GlaxoSmithKline. Zentel (Albendazole) product information. Product monograph version 3.0. 2011. Available at: http://www.gsk.com.au/resources.ashx/prescriptionmedicinesproductschilddataproinfo/1252/FileName/214005870BB4EF194E1B5C2A6F986051/Zentel_PI_-_clean.pdf. Accessed 18 Oct 2014.

  5. Janssen. Vermox. Product monograph. 2013. Available at: http://www.janssen.ca/subcategory_docdownload?id=1747. Accessed 18 Oct 2014.

  6. Dayan AD. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica. 2003;86:141–59.

    Article  CAS  PubMed  Google Scholar 

  7. Li X-Q, Björkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003;59(5–6):429–42.

    Article  CAS  PubMed  Google Scholar 

  8. Chen K, Twu S, Chang H, Lin R. Outbreak of Stevens–Johnson syndrome/toxic epidermal necrolysis associate with mebendazole and metronidazole use among Filipino laborers in Taiwan. Am J Pub Health. 2003;93:489–92.

    Article  Google Scholar 

  9. Schipper H, Koopmans R, Nagy J. Effect of dose increase or cimetidine co-administration on albendazole bioavailability. Am J Trop Med Hyg. 2000;63(5, 6):270–3.

    CAS  PubMed  Google Scholar 

  10. Nagy J, Schipper HG, Koopmans RP, Butter JJ, van Boxtel CJ, Kager PA. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg. 2002;66:260–3.

    CAS  PubMed  Google Scholar 

  11. Takayanagui OM, Lanchote VL, Marques MP, Bonato PS. Therapy for neurocysticercosis: pharmacokinetic interaction of albendazole sulfoxide with dexamethasone. Ther Drug Monit. 1997;19:51–5.

    Article  CAS  PubMed  Google Scholar 

  12. Jung H, Hurtado M, Tulio Medina M, Sanchez M, Sotelo J. Dexamethasone increases plasma levels of albendazole. J Neurol. 1990;237:279–80.

    Article  CAS  PubMed  Google Scholar 

  13. Corti N, Heck A, Rentsch K, Zingg W, Jetter A, Stieger B, et al. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers. Eur J Clin Pharmacol. 2009;65:999–1006.

    Article  CAS  PubMed  Google Scholar 

  14. Lanchote VL, Garcia FS, Dreossi SA, Takayanagui OM. Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis. Ther Drug Monit. 2002;24:338–45.

    Article  CAS  PubMed  Google Scholar 

  15. Awadzi K, Edwards G, Duke BOL, Opoku NO, Attah SK, Addy ET, et al. The co-administration of ivermectin and albendazole: safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003;97:165–78.

    Article  CAS  PubMed  Google Scholar 

  16. Homeida M, Leahy W, Copeland S, Ali MM, Harron DW. Pharmacokinetic interaction between praziquantel and albendazole in Sudanese men. Ann Trop Med Parasitol. 1994;88:551–9.

    CAS  PubMed  Google Scholar 

  17. Lima RM, Ferreira MAD, de Jesus Ponte Carvalho TM, Dumêt Fernandes BJ, Takayanagui OM, Garcia HH, et al. Albendazole–praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity. Br J Clin Pharmacol. 2011;71:528–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Pengsaa K, Na-Bangchang K, Limkittikul K, Kabkaew K, Lapphra K, Sirivichayakul C, et al. Pharmacokinetic investigation of albendazole and praziquantel in Thai children infected with Giardia intestinalis. Ann Trop Med Parasitol. 2004;98:349–57.

    Article  CAS  PubMed  Google Scholar 

  19. Na-Bangchang K, Kietinun S, Pawa KK, Hanpitakpong W, Na-Bangchang C, Lazdins J. Assessments of pharmacokinetic drug interactions and tolerability of albendazole, praziquantel and ivermectin combinations. Trans R Soc Trop Med Hyg. 2006;100:335–45.

    Article  CAS  PubMed  Google Scholar 

  20. Garcia HH, Lescano AG, Lanchote VL, Pretell EJ, Gonzales I, Bustos JA, et al. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis. Br J Clin Pharmacol. 2011;72:77–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Shenoy RK, Suma TK, John A, Arun SR, Kumaraswami V, Fleckenstein LL, et al. The pharmacokinetics, safety and tolerability of the co-administration of diethylcarbamazine and albendazole. Ann Trop Med Parasit. 2002;96:603–14.

    Article  CAS  PubMed  Google Scholar 

  22. Amsden GW, Gregory TB, Michalak CA, Glue P, Knirsch CA. Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers. Am J Trop Med Hyg. 2007;76:1153–7.

    CAS  PubMed  Google Scholar 

  23. Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, et al. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004;98:595–614.

    Article  CAS  PubMed  Google Scholar 

  24. Luder PJ, Siffert B, Witassek F, Meister F, Bircher J. Treatment of hydatid disease with high oral doses of mebendazole. Eur J Clin Pharmacol. 1986;31:443–8.

    Article  CAS  PubMed  Google Scholar 

  25. Bekhti A, Pirotte J. Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts. Br J Clin Pharmacol. 1987;24:390–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Merino G, Molina A, García JL, Pulido MM, Prieto JG, Alvarez AI. Ginseng increases intestinal elimination of albendazole sulfoxide in the rat. Comp Biochem Physiol Part C Toxicol Pharmacol. 2003;136:9–15.

    Article  Google Scholar 

  27. Merino G, Molina AJ, Garcia JL, Pulido MM, Prieto JG, Alvarez A. Intestinal elimination of albendazole sulfoxide: pharmacokinetic effects of inhibitors. Int J Pharm. 2003;263:123–32.

    Article  CAS  PubMed  Google Scholar 

  28. Atef M, El-Gendi AY, Amer AM, Abd El-Aty AM. Effect of three anthelmentics on disposition kinetics of florfenicol in goats. Food Chem Toxicol. 2010;48:3340–4.

    Article  CAS  PubMed  Google Scholar 

  29. El-Sooud K. Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats. Pharmacol Res. 2003;48:389–95.

    Article  CAS  Google Scholar 

  30. Virkel G, Lifschitz A, Sallovitz J, Inza G, Lanusse C. Effect of the ionophore antibiotic monensin on the ruminal biotransformation of benzimidazole anthelmintics. Vet J. 2004;167:265–71.

    Article  CAS  PubMed  Google Scholar 

  31. Alvarez L, Lifschitz A, Entrocasso C, Manazza J, Mottier L, Borda B, et al. Evalutaion of the interaction between ivermectin and albendazole following their combined use in lambs. J Vet Pharmacol Ther. 2008;31:230–9.

    Article  CAS  PubMed  Google Scholar 

  32. Merino G, Molina AJ, Garcia JL, Pulido MM, Prieto JG, Alvarez AI. Effect of clotrimazole on microsomal metabolism and pharmacokinetics of albendazole. J Pharm Pharmacol. 2003;55:757–64.

    Article  CAS  PubMed  Google Scholar 

  33. López-García ML, Torrado S, Martínez AR, Bolás F. Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime. Vet Parasitol. 1998;75:209–19.

    Article  PubMed  Google Scholar 

  34. Merino G, Alvarez A, Prieto J, Kim R. The anthelminthic agent albendazole does not interact with p-glycoprotein. Drug Metab Dispos. 2002;30(4):365–9.

    Article  CAS  PubMed  Google Scholar 

  35. Wen H, Zhang HW, Muhmut M, Zou PF, New RR, Craig PS. Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. Ann Trop Med Parasitol. 1994;88:49–52.

    CAS  PubMed  Google Scholar 

  36. Schneider D, Gannon R, Sweeney K, Shore E. Theophylline and antiparasitic drug interactions. Chest. 1990;97:84–7.

    Article  CAS  PubMed  Google Scholar 

  37. Adebayo G, Mabadeje A. Theophylline disposition: effects of cimetidine, mebendazole and albendazole. Aliment Pharmacol Ther. 1988;2:341–6.

    Article  CAS  PubMed  Google Scholar 

  38. Lange H, Eggers R, Bircher J. Increased systemic availability of albendazole when taken with a fatty meal. Eur J Clin Pharmacol. 1988;34:315–7.

    Article  CAS  PubMed  Google Scholar 

  39. Mares SS, Jung CH, López AT, González-Esquivel DF. Influence of a Mexican diet on the bioavailability of albendazole. Basic Clin Pharmacol Toxicol. 2005;97:122–4.

    Article  CAS  PubMed  Google Scholar 

  40. Jung H, Medina L, García L, Fuentes I, Moreno-Esparza R. Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide. J Pharm Pharmacol. 1998;50:43–8.

    Article  CAS  PubMed  Google Scholar 

  41. Gottschall DW, Theodorides VJ, Wang R. The metabolism of benzimidazole anthelmintics. Parasitol Today. 1990;6:115–24.

    Article  CAS  PubMed  Google Scholar 

  42. Li X-Q, Björkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003;59:429–42.

    Article  CAS  PubMed  Google Scholar 

  43. Moroni P, Buronfosse T. Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes. Drug Metab Dispos. 1995;23:160–5.

    CAS  PubMed  Google Scholar 

  44. Lin JH, Lu AYH. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 1998;35:361–90.

    Article  CAS  PubMed  Google Scholar 

  45. McCune JS, Hawke RL, Lecluyse EL. In vivo and in vitro induction of human cytochrome P450 3A4 by dexamethasone. Clin Pharmacol Ther. 2000;68:356–66.

    Article  CAS  PubMed  Google Scholar 

  46. Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, et al. Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr. 2006;42:52–60.

    CAS  PubMed  Google Scholar 

  47. Lin JH, Lu AYH. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 1998;35:361–90.

    Article  CAS  PubMed  Google Scholar 

  48. Riva R, Albani F, Contin M, Baruzzi A. Pharmacokinetic interactions between antiepileptic drugs. Clin Pharmacokinet. 1996;31:470–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar

    Shane Ashley Pawluk & Kyle John Wilby

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada

    Craig Allan Roels & Mary H. H. Ensom

Authors
  1. Shane Ashley Pawluk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Craig Allan Roels
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyle John Wilby
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mary H. H. Ensom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shane Ashley Pawluk.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pawluk, S.A., Roels, C.A., Wilby, K.J. et al. A Review of Pharmacokinetic Drug–Drug Interactions with the Anthelmintic Medications Albendazole and Mebendazole. Clin Pharmacokinet 54, 371–383 (2015). https://doi.org/10.1007/s40262-015-0243-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40262-015-0243-9

Keywords

Search

Navigation