Continuing Education Activity

Albendazole is an FDA-approved medication for treating a variety of parasitic worm infections. Albendazole is an antihelminthic medication with numerous indications such as cystic hydatid disease of the liver, lung, and peritoneum resulting from the larval form of the dog tapeworm, Echinococcus granulosus. Albendazole also has approval for treating parenchymal neurocysticercosis secondary to active lesions caused by infection with larval forms of the pork tapeworm, Taenia solium. This activity will discuss the role of the interprofessional team in the use of this medication.

Objectives:

• Identify the mechanism of action of albendazole.
• Describe the potential adverse effects of albendazole.
• Review the approved and off-label indications of albendazole.
• Identify some interprofessional team strategies for improving care coordination and communication to advance albendazole therapy and improve outcomes.

Indications

Albendazole is an FDA-approved medication for the treatment of a variety of parasitic worm infections. Albendazole is an antihelminthic medication with numerous indications such as cystic hydatid disease of the liver, lung, and peritoneum resulting from the larval form of the dog tapeworm, Echinococcus granulosus. Albendazole also has approval for treating parenchymal neurocysticercosis secondary to active lesions caused by infection with larval forms of the pork tapeworm, Taenia solium. It can also be a valuable agent for the treatment of pinworm disease caused by Enterobius vermicularis.

Albendazole is used to treat Trichuriasis (Trichuris trichiuria), Filiariasis, Ascariasis (Ascaris lumbricoides), and metronidazole-resistant Giardiasis (Giardia duodenalis). 

Finally, it can be prescribed as a treatment for Trichinosis (Trichinella spiralis), hookworms (Ancylostoma sp. and Necator sp.), and Strongyloidiasis (Strongyloides stercoralis).[1]

Albendazole has also been the topic of recent investigation as a potential anticancer agent due to its limited toxicity to normal cells but high toxicity to both tumor and parasitic cells.[2] Recent studies have created nanoformulations of albendazole and conjugated the drug to nano-carriers to improve solubility and increase drug delivery to tumor cells.[2]

Albendazole and mebendazole have demonstrated anticancer properties in vitro and in animal models. Both have demonstrated anticancer properties against the following solid tumor cancers: breast, head and neck, colorectal, melanoma, ovary, and prostate. There is also limited clinical data on albendazole and mebendazole’s anticancer properties. Neutropenia is a limiting side effect of prolonged high dose albendazole pharmacotherapy. Mebendazole appears less likely to cause neutropenia.[3]

Keller L. et al. conducted double-blind, randomized controlled trials on the effectiveness of albendazole-ivermectin versus albendazole-placebo in the treatment of Trichuris trichiura. The patients, ages 6 to 60, were from Lao People's Democratic Republic (Laos) and Tanzania (Pemba Island). In Laos, 466 patients received the combination of albendazole-ivermectin, and 413 patients received albendazole-placebo treatment. In Tanzania, 558 patients received the combination of albendazole-ivermectin, and 515 patients received albendazole-placebo treatment. Patients were assessed at six months and twelve months post-treatment. A minimum of one stool specimen was collected from each patient who underwent Kato-Katz assessment, and helminth egg reduction rates, reinfection rates, and cure rates were determined. Patients who were helminth positive after six months received additional treatment. The helminth egg reduction rates in patients from Laos at six months were 99 vs. 79.6 % in albendazole-ivermectin versus albendazole-placebo, respectively. The cure rates were 65.8 vs. 13.4% in albendazole-ivermectin versus albendazole-placebo, respectively. The helminth egg reduction rates in patients from Tanzania at six months were 84.9 vs. 21.2% in albendazole-ivermectin versus albendazole-placebo, respectively. The cure rates were 17.8 vs. 1.4% in albendazole-ivermectin versus albendazole-placebo, respectively. The reinfection rate was 10% in Laos and 100% in Tanzania at twelve months for the albendazole-placebo cohort. Keller L. et al. concluded that albendazole-ivermectin treatment was superior to albendazole-placebo treatment regarding Trichuris trichiura egg reduction rates, reinfection rates, and cure rates.[4]

Mechanism of Action

Albendazole sulfoxide, the active metabolite of albendazole, causes selective degeneration of cytoplasmic microtubules in intestinal and tegmental cells of intestinal helminths and larvae. The metabolite binds to the B-tubulin subunit of the helminth's microtubules and thus inhibits microtubule polymerization.[5] 

Albendazole also causes impaired glucose utilization and causes a decrease in the parasite's glycogen stores. At high concentrations, albendazole inhibits parasitic metabolic pathways such as the Kreb cycle by inhibiting key enzymes such as malate dehydrogenase. A subsequent decrease in ATP production occurs, which causes energy depletion, leading to the immobilization of the parasite and subsequent death.[5]

Administration

Albendazole comes in a variety of formulations ranging from tablets to oral solutions. A limiting factor in dosing albendazole is its poor solubility and absorption in the human body.[6] Consequently, albendazole should be administered with a high-fat meal to improve its bioavailability.[6] To treat an intraluminal infection, albendazole administration should be on an empty stomach to maximize absorption. The tablets can be crushed or chewed and then swallowed with a drink of water if the patient has difficulty swallowing. An oral suspension of albendazole is also an option if the patient has swallowing dysfunction or is at risk for aspiration. Researchers are developing new formulations of albendazole that have micro-emulsifying delivery systems and increased lipid-solubility to maximize the therapeutic efficacy of the drug.[7]

Care is necessary when albendazole is coadministered with medications that interact with the cytochrome P450 pathway as the CYP450 system of enzymes metabolizes albendazole. CYP450 inducing medications such as phenobarbital, phenytoin, rifampin, and carbamazepine can lower the concentration of albendazole by as much as 50%.[5] CYP450 inhibitors such as cimetidine and grapefruit juice can increase the concentration and availability of albendazole by as much as 50% as well.[8]

Commonly, clinicians coadminister steroids such as dexamethasone with albendazole to treat neuro-helminth infections to increase the bioavailability of albendazole, reduce inflammation, and decrease cerebral edema.[9] Corticosteroids have demonstrated a capacity to increase the efficacy of the treatment, reduce complications, and improve patient outcomes when coadministered with albendazole.[9]

Adverse Effects

The most common adverse effects accompanying albendazole use are headaches and elevated liver enzymes, with 10% to 20% of patients experiencing elevated liver enzymes.[10][11] Some other side effects of albendazole include abdominal pain, nausea, vomiting, and fever. A small percentage of patients may experience a hypersensitivity reaction such as hives and pruritus to the drug. There are reports of alopecia and telogen effluvium in the literature as rare side effects of albendazole therapy. Fortunately, alopecia and telogen effluvium usually reverse after completing the treatment.[10]

Other serious side effects include leukopenia, anemia, thrombocytopenia, and pancytopenia, with patients who have preexisting liver damage or dysfunction at the highest risk for developing these conditions.[12] The most likely mechanism is that albendazole-induced myelosuppression results from the drug's beta-tubulin inhibition affecting the host's microtubules and thus inhibiting the activity of actively dividing human cells such as white blood cells.[12]

Patients with neuro-helminth infection may experience symptoms such as focal neurologic deficits, seizures, and headaches more frequently compared to other parasitic infections due to the destruction of helminthic larvae and cysts in the brain. They also may experience meningeal signs and increased intracranial pressure due to the local inflammatory reaction from parasite death. Mitigating these symptoms is possible with the coadministration of steroids and anticonvulsant medication. 

Contraindications

Albendazole is contraindicated in patients with a history of hypersensitivity to albendazole, benzimidazoles, or any component of the formulation. Clinicians should use the drug with caution in patients with active liver disease or dysfunction because the liver metabolizes the drug via the CYP450 system.[5] Also, care is in order if the patient has biliary obstruction as the drug gets significantly excreted in bile.

The FDA classified albendazole as a category C drug under the prior pregnancy rating system, which states the drug should be avoided during pregnancy and reserved only for use in pregnant patients if there is not an acceptable alternative available. Studies in rats have shown some teratogenic effects in the offspring of rats that received the drug; however, some studies of pregnant patients that received albendazole did not show an increased risk of teratogenicity with exposure to the drug. More research is necessary as there are very few articles in the literature about the potential effects on pregnancy and the developing fetus.[13] 

Monitoring

Liver function tests and CBC with differential should be performed at the start of a 28-day cycle and every two weeks during therapy due to the risk of pancytopenia and anemia.[13][12] Patients with a predisposition for leukopenia and pancytopenia, such as patients with recent chemotherapy, should be observed closely due to the potential of albendazole-induced myelosuppression. Patients with liver disease require more frequent monitoring because the drug is metabolized primarily by the liver.[6] Before initiating therapy, ophthalmic exams for retinal lesions should also be performed in patients with neurocysticercosis because the destruction of parasites in the eye can cause retinal damage. 

Toxicity

Albendazole's low solubility prevents it from being absorbed in large enough quantities to be toxic to humans. There is no specific antidote for albendazole overdose.[14]

Enhancing Healthcare Team Outcomes

Albendazole is one of the most used antiparasitic drugs used throughout the world due to its low cost and high efficacy. Most of the time, this drug is well-tolerated with very few side effects; however, this drug should not be used without physician monitoring or approval due to the risk of severe side effects such as pancytopenia; this effort requires an interprofessional team. Patients with liver dysfunction require regular liver function tests and monitoring due to the increased risk of side effects. [Level 3]

Pharmacists can make a significant contribution to the care of patients taking albendazole by creating the proper formulation for the patient to administer. For example, patients with high aspiration risks or swallowing dysmotility can benefit from oral suspensions, and children can benefit from dissolved tablets or oral suspensions as well to increase their adherence to drug therapy. They can also check for potential drug-drug interactions and serve as a point of patient counsel about the medication and how to take it.

For patients with neurologic involvement, ophthalmologists can observe potential retinal progression and resolution of the disease. Infectious disease specialists can coordinate care with primary care providers to ensure proper infection treatment. Nurses are integral in the treatment process as they are often the direct interface with the patient and can obtain information regarding medication side effects and patient adherence. With interprofessional management and monitoring, albendazole therapy has its best chance of achieving positive patient outcomes. [Level 5]

Review Questions

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References

1.

Henriquez-Camacho C, Gotuzzo E, Echevarria J, White AC, Terashima A, Samalvides F, Pérez-Molina JA, Plana MN. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection. Cochrane Database Syst Rev. 2016 Jan 18;2016(1):CD007745. [PMC free article: PMC4916931] [PubMed: 26778150]

2.

Movahedi F, Li L, Gu W, Xu ZP. Nanoformulations of albendazole as effective anticancer and antiparasite agents. Nanomedicine (Lond). 2017 Oct;12(20):2555-2574. [PubMed: 28954575]

3.

Chai JY, Jung BK, Hong SJ. Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update. Korean J Parasitol. 2021 Jun;59(3):189-225. [PMC free article: PMC8255490] [PubMed: 34218593]

4.

Keller L, Welsche S, Patel C, Sayasone S, Ali SM, Ame SM, Hattendorf J, Hürlimann E, Keiser J. Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: Results from randomized controlled trials in Lao PDR and Pemba Island, Tanzania. PLoS Negl Trop Dis. 2021 Jun;15(6):e0009561. [PMC free article: PMC8277064] [PubMed: 34191812]

5.

Venkatesan P. Albendazole. J Antimicrob Chemother. 1998 Feb;41(2):145-7. [PubMed: 9533454]

6.

Zhang H, Liu C, Zheng Q. Development and application of anthelminthic drugs in China. Acta Trop. 2019 Dec;200:105181. [PubMed: 31542370]

7.

Sawatdee S, Atipairin A, Sae Yoon A, Srichana T, Changsan N, Suwandecha T. Formulation Development of Albendazole-Loaded Self-Microemulsifying Chewable Tablets to Enhance Dissolution and Bioavailability. Pharmaceutics. 2019 Mar 20;11(3) [PMC free article: PMC6471907] [PubMed: 30897738]

8.

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 Mar;66(3):260-3. [PubMed: 12139218]

9.

Romo ML, Carpio A, Kelvin EA. Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel? J Clin Pharmacol. 2014 Apr;54(4):361-7. [PubMed: 24443292]

10.

Veraldi S, Francia C, La Vela V, Nazzaro G, Barbareschi M. Telogen effluvium after oral albendazole. Clin Exp Dermatol. 2012 Jul;37(5):565-7. [PubMed: 22420487]

11.

Speich B, Ali SM, Ame SM, Bogoch II, Alles R, Huwyler J, Albonico M, Hattendorf J, Utzinger J, Keiser J. Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial. Lancet Infect Dis. 2015 Mar;15(3):277-84. [PubMed: 25589326]

12.

Xing F, Ye H, Yang J, Chan JF, Seto WK, Pai PM, Yuen KY, Hung DL. Fatal pancytopenia due to albendazole treatment for strongyloidiasis. IDCases. 2018;12:112-116. [PMC free article: PMC6010955] [PubMed: 29942764]

13.

Choi JS, Han JY, Ahn HK, Ryu HM, Koren G. Foetal outcomes after exposure to albendazole in early pregnancy. J Obstet Gynaecol. 2017 Nov;37(8):1108-1111. [PubMed: 28760057]

14.

Dayan AD. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Trop. 2003 May;86(2-3):141-59. [PubMed: 12745134]

15.

Curtiss P, Cobos G, Sicco KL, Seminara N. Acute Alopecia Associated With Albendazole Toxicosis. Cutis. 2022 May;109(5):E43-E45. [PubMed: 35856765]

16.

Garg D, Sharma S. Albendazole for Neurocysticercosis in Children: How Long is Long Enough? Indian Pediatr. 2022 Dec 15;59(12):909-910. [PubMed: 36511204]

17.

Jacob J, Steel A, Lin Z, Berger F, Zöeller K, Jarvi S. Clinical Efficacy and Safety of Albendazole and Other Benzimidazole Anthelmintics for Rat Lungworm Disease (Neuroangiostrongyliasis): A Systematic Analysis of Clinical Reports and Animal Studies. Clin Infect Dis. 2022 Apr 09;74(7):1293-1302. [PMC free article: PMC8994584] [PubMed: 34448480]

Disclosure: Kashif Malik declares no relevant financial relationships with ineligible companies.

Disclosure: Anterpreet Dua declares no relevant financial relationships with ineligible companies.