Continuing Education Activity
Albendazole has FDA approval for the treatment of cystic hydatid disease of the liver, lung, and peritoneum resulting from the larval form of the dog tapeworm, Echinococcus granulosus. Albendazole is also approved for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium. This activity will discuss the role of the interprofessional team in the use of this medication.
- Identify the mechanism of action and administration of albendazole.
- Describe the adverse effects and contraindications of albendazole.
- Review the appropriate monitoring and toxicity of albendazole.
- Identify some interprofessional team strategies for improving care coordination and communication to advance albendazole therapy and improve outcomes.
Albendazole is an FDA-approved medication for the treatment of a variety of parasitic worm infections. Albendazole is an antihelminthic medication that has 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 the treatment of parenchymal neurocysticercosis secondary to active lesions caused by infection with larval forms of the pork tapeworm, Taenia solium. It is also useful in 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).
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. Recent studies have created nanoformulations of albendazole and conjugated the drug to nano-carriers to improve solubility and increase drug delivery to tumor cells.
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. 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, which leads to the immobilization of the parasite and subsequent death.
Albendazole comes in a variety of formulations ranging from tablets to oral solutions. A limiting factor of albendazole is its poor solubility and absorption in the human body. Consequently, albendazole should be administered with a high-fat meal to improve its bioavailability. 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.
Care is necessary when albendazole coadministering 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%. CYP450 inhibitors such as cimetidine and grapefruit juice can increase the concentration and availability of albendazole by as much as 50% as well.
Commonly, clinicians coadminister steroids such as dexamethasone with albendazole for the treatment of neuro-helminth infections to increase the bioavailability of albendazole, reduce inflammation, and decrease cerebral edema. Corticosteroids have demonstrated a capacity to increase the efficacy of the treatment, reduce complications, and improve patient outcomes when coadministered with albendazole.
The most common adverse effects accompanying albendazole use are headaches and elevated liver enzymes, with 10% to 20% of patients experiencing elevated liver enzymes. 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.
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. 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.
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. Mitigation of these symptoms is possible with the coadministered with steroids and anticonvulsant medication.
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. 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.
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. 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. 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.
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.
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. The majority 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 be involved in the care of a patient 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.
For patients with neurologic involvement, ophthalmologists can observe potential retinal progression and resolution of the disease, and infectious disease specialists can coordinate care with primary care providers to ensure proper treatment of the infection. 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]