Albendazole

Albendazole is an anthelmintic agent belonging to the pharmacological class of Benzimidazole

Albendazole has been approved to relieve symptoms and also for the treatment and maintenance of Ancylostoma caninum, Ancylostoma duodenale or Necator americanus, Ascariasis, Clonorchis sinensis or Opisthorchis viverrini, Cutaneous larva migrans, Enterobiasis, Giardiasis, Gnathostomiasis, Gongylonemiasis, Hydatid disease, Microsporidiosis, Neurocysticercosis, parenchymal disease, Oesophagostomum bifurcum, Taeniasism, Toxocariasis, Trichinellosis.

Albendazole is a medication that is generally well-tolerated by patients. Its absorption from the gastrointestinal tract is limited due to its low aqueous solubility. However, taking albendazole with a fatty meal can enhance its oral bioavailability. The drug is primarily metabolized in the liver, where it is rapidly converted to the main metabolite, albendazole sulfoxide. This metabolite is further transformed into albendazole sulfone and other primary oxidative metabolites, which are then excreted in human urine. Approximately 70% of albendazole is bound to plasma proteins. Although the volume of distribution is not available, it is important to note that albendazole selectively damages cytoplasmic microtubules in the absorptive and intestinal cells of nematodes without affecting the host's cells. This disruption of microtubules leads to a breakdown of essential functions in the helminth, resulting in its immobilization and eventual death. The elimination of albendazole and its metabolites occurs mainly through urine, with urinary excretion of albendazole sulfoxide being a minor pathway. The drug's efficacy can vary depending on the type of infection, and it may take up to three days for patients to experience its therapeutic effects.

The common side effects involved in using Albendazole are Headache, Dizziness, Nausea, Vomiting, Stomach and abdominal pain, Temporary hair loss.

Albendazole is available in the form of Delayed-release Tablets and syrups.

Albendazole is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Albendazole belonging to the pharmacological class of Triazoles, acts as an anthelmintic agent.

Benzimidazole antihelmintic agents work by inhibiting the polymerization of tubulin and the uptake of glucose that relies on microtubules, achieved through binding to free ß-tubulin. In the case of albendazole, it selectively targets and damages the cytoplasmic microtubules in the absorptive and intestinal cells of nematodes while sparing the host's cells. This damage to the microtubules is irreversible and disrupts the essential functions of these cells, leading to the accumulation of secretory substances in the Golgi apparatus, reduced glucose uptake, and depletion of the helminth's glycogen stores. As a result, the parasite's energy production is diminished, causing it to become immobilized and eventually leading to its demise.

Albendazole exhibits larvicidal effects in necatoriasis and ovicidal effects in ascariasis, ancylostomiasis, and trichuriasis. However, it is worth noting that resistance to albendazole has been observed in animals, and this resistance is attributed to the loss of affinity to tubulin binding sites.

Albendazole has been approved to relieve symptoms and also for the treatment and maintenance of Ancylostoma caninum, Ancylostoma duodenale or Necator americanus, Ascariasis, Clonorchis sinensis or Opisthorchis viverrini, Cutaneous larva migrans, Enterobiasis, Giardiasis, Gnathostomiasis, Gongylonemiasis, Hydatid disease, Microsporidiosis, Neurocysticercosis, parenchymal disease, Oesophagostomum bifurcum, Taeniasism, Toxocariasis, Trichinellosis.

After taking a single 400 mg dose of the parent drug, the peak plasma concentration of albendazole sulphoxide is typically observed in the range of 0.22-0.25 mg/L approximately two to three hours after the dose administration.

Albendazole is generally well-tolerated, and the time it takes for the effects to be noticeable may vary depending on the type of infection you have. It might take up to three days before a person start experiencing the effects of albendazole.

Albendazole is found to be available in the form of Tablets and Syrups.

Albendazole can be used in the following treatment:

• Ancylostoma caninum
• Ancylostoma duodenale or Necator americanus
• Ascariasis
• Clonorchis sinensis or Opisthorchis viverrini
• Cutaneous larva migrans
• Enterobiasis
• Giardiasis
• Gnathostomiasis
• Gongylonemiasis
• Hydatid disease
• Microsporidiosis
• Neurocysticercosis, parenchymal disease
• Oesophagostomum bifurcum
• Taeniasis
• Toxocariasis
• Trichinellosis

Albendazole is approved for use in the following clinical indications:

• Ancylostoma caninum
• Ancylostoma duodenale or Necator americanus
• Ascariasis
• Clonorchis sinensis or Opisthorchis viverrini
• Cutaneous larva migrans
• Enterobiasis
• Giardiasis
• Gnathostomiasis
• Gongylonemiasis
• Hydatid disease
• Microsporidiosis
• Neurocysticercosis, parenchymal disease
• Oesophagostomum bifurcum
• Taeniasis
• Toxocariasis
• Trichinellosis

Ancylostoma caninum (eosinophilic enterocolitis)

• Oral: 400 mg as a single dose.

Ancylostoma duodenale or Necator americanus (hookworms)

• Oral: 400 mg as a single dose.

Ascariasis (intestinal roundworm)

• Oral: 400 mg as a single dose.

Clonorchis sinensis or Opisthorchis viverrini (Chinese liver fluke or Southeast Asian liver fluke)

• Oral: 10 mg/kg/day for 7 days.

Cutaneous larva migrans (dog and cat hookworm)

• Oral: 400 mg once daily for three days.

Enterobiasis (pinworm)

• Oral: 400 mg as a single dose; repeat in two weeks.

Giardiasis (Giardia duodenalis) (alternative agent)

• Oral: 400 mg once daily for five days.

Gnathostomiasis (Gnathostoma spinigerum)

• Oral: 400 mg twice daily for 21 days.

Gongylonemiasis (Gongylonema spp.)

• Oral: 400 mg once daily for three days.

Hydatid disease (Echinococcus granulosis, dog tapeworm)

• <60 kg: 15 mg/kg/day in two divided doses (maximum: 800 mg/day).
• ≥60 kg: 800 mg/day in two divided doses.
• Duration: Optimal duration uncertain; 1 to 6 months based on clinical factors.

Microsporidiosis

Immunocompetent patients:

• Disseminated infection: Oral: 400 mg twice daily.
• Intestinal (Encephalitozoon intestinalis) infection: Oral: 400 mg twice daily for 21 days.
• Ocular infection: Oral: 400 mg twice daily, in combination with topical fumagillin.

Immunocompromised patients (e.g., patients with HIV):

• Disseminated or intestinal infection (other than Enterocytozoon bieneusi or Vittaforma corneal): Oral: 400 mg twice daily for 21 days; for patients with HIV, continue until CD4 count >200 cells/mm3 for >6 months after initiation of antiretroviral therapy.
• Ocular infection: Oral: 400 mg twice daily, in combination with topical fumagillin; continue until resolution of ocular symptoms and until CD4 count >200 cells/mm3 for >6 months after initiation of antiretroviral therapy.

Neurocysticercosis, parenchymal disease (Taenia solium, pork tapeworm)

• Oral: 15 mg/kg/day in 2 divided doses (maximum: 1.2 g/day) for 10 to 14 days; may be repeated if persistent viable lesions on 6-month follow-up imaging. Concomitant therapy with praziquantel is recommended if >2 viable cysts are present. Initiate adjunctive corticosteroid therapy prior to initiation of albendazole. Antiparasitic therapy should not be initiated in patients with untreated hydrocephalus, calcified lesions, or cysticerci encephalitis; consult an infectious diseases specialist for specific treatment recommendations.

Oesophagostomum bifurcum

• Oral: 400 mg as a single dose.

Taeniasis (alternative agent)

• Oral: 400 mg once daily for three days.

Toxocariasis

• Ocular larva migrans with sight-threatening ocular inflammation: Oral: Optimal dose is unknown: 400 mg twice daily for 2 weeks; 800 mg twice daily has also been described. Give with concomitant corticosteroids.
• Visceral larva migrans, moderate to severe: Oral: 400 mg twice daily, generally for 5 days; consider concomitant corticosteroids for severe infection.

Trichinellosis (Trichinella spiralis)

• Oral: 400 mg twice daily for 8 to 14 days; concomitant corticosteroids may be given for severe symptoms.

Albendazole is available in the following dosage forms and strengths:

• Tablets : 200mg
• Syrups: 200mg/5ml

When taking Albendazole, there are certain dietary restrictions that should be followed to ensure the medication's effectiveness and safety:

• Food with High Fat Content: Albendazole oral bioavailability appears to be enhanced when taken with a fatty meal. Therefore, it is recommended to take albendazole with food that contains a moderate to high amount of fat (e.g., a meal with approximately 40 grams of fat) to improve its absorption and effectiveness.

The dietary restriction should be individualized as per patient requirements.

Albendazole may be contraindicated under the following conditions:

• Albendazole is not recommended for use in patients who have a known hypersensitivity to the benzimidazole class of compounds or any components present in Albendazole.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

WARNINGS

There have been reports of rare fatalities associated with the use of Albendazole due to granulocytopenia or pancytopenia. It has been found that Albendazole can lead to bone marrow suppression, aplastic anemia, and agranulocytosis in patients with or without underlying hepatic dysfunction. To ensure patient safety, blood counts should be closely monitored at the start of each 28-day cycle of therapy and every two weeks while on therapy with albendazole. Patients with liver disease, including hepatic echinococcosis, should be monitored even more closely as they are at a higher risk for bone marrow suppression, leading to pancytopenia, aplastic anemia, agranulocytosis, as well as leukopenia. If any clinically significant decreases in blood cell counts occur, albendazole should be discontinued immediately.

Pregnant women should not use albendazole except in specific clinical circumstances where no other management is appropriate. Additionally, patients should avoid becoming pregnant for at least a month following the cessation of albendazole therapy. In the event that a patient becomes pregnant while taking this drug, albendazole should be stopped immediately and the potential hazard to the fetus should be explained to the patient.

PRECAUTIONS

Patients receiving treatment for neurocysticercosis should be given steroid and anticonvulsant therapy as necessary. To prevent cerebral hypertensive episodes during the first week of anticysticeral therapy, corticosteroids (oral or intravenous) should be considered. When treated with albendazole for other conditions, patients may reveal pre-existing neurocysticercosis. Symptoms such as seizures, increased intracranial pressure, and focal signs may occur due to an inflammatory reaction caused by the parasite's death within the brain. If symptoms occur soon after treatment, immediate initiation of appropriate steroid and anticonvulsant therapy is recommended

. There is a rare possibility that cysticercosis may affect the retina. Patients should be examined for retinal lesions before initiating therapy for neurocysticercosis. If such lesions are found, the need for anticysticeral therapy should be evaluated against the likelihood of retinal damage caused by albendazole-induced changes to the retinal lesion.

Patients should be informed that:

• Some people, especially young children, may have difficulty swallowing the tablets whole. In young children, the tablets can be crushed or chewed and swallowed with water.
• To ensure the safety of unborn babies, it is recommended that women of childbearing age only begin taking albendazole after receiving a negative pregnancy test.
• It is important for these women to avoid getting pregnant while taking albendazole and for one month after completing the treatment.
• Regular monitoring of blood counts and liver function tests every two weeks is necessary during albendazole therapy as there is a potential for liver or bone marrow damage. To avoid any harm to a fetus, if you are a woman of childbearing age, it is recommended that you take a pregnancy test before starting treatment with Albendazole. It is also advised that you do not become pregnant while taking Albendazole or within a month of completing treatment. During Albendazole therapy, it is important to undergo regular blood count and liver function tests every two weeks to ensure that the liver and bone marrow are not negatively affected.
• Albendazole should be taken with food.

It is advisable to avoid alcohol consumption during Albendazole treatment, as it may increase the risk of liver toxicity and other adverse effects.

Albendazole is excreted in animal milk, but it is currently unknown whether it is excreted in human milk. Given that many drugs are excreted in human milk, caution should be exercised when administering albendazole to a nursing woman.

Pregnancy:

Pregnancy Category C

It has been found that Albendazole can cause birth defects and skeletal abnormalities in pregnant rats and rabbits. When given orally at doses of 10 and 30 mg/kg/day during gestation days 6 to 15 in rats, and at a dose of 30 mg/kg/day during gestation days 7 to 19 in rabbits, teratogenic effects were observed. Maternal toxicity was also noted in the rabbit study, with a 33% mortality rate at the 30 mg/kg/day dose. However, no such effects were observed in mice at oral doses up to 30 mg/kg/day administered during gestation days 6 to 15.

There have not been enough studies on the effects of albendazole on pregnant women to make a definitive conclusion. Therefore, using albendazole during pregnancy should only be considered if the potential benefits outweigh the potential risks to the fetus. Caution and careful evaluation of the situation are necessary in these cases.

There are certain food-related warnings and precautions to consider when using Albendazole:

• Food with High Fat Content: Albendazole oral bioavailability appears to be enhanced when taken with a fatty meal. Therefore, it is recommended to take albendazole with food that contains a moderate to high amount of fat (e.g., a meal with approximately 40 grams of fat) to improve its absorption and effectiveness.

The adverse reactions related to Albendazole can be categorized as follows:

Common:

• Nausea
• Vomiting
• Stomach and abdominal pain

Less Common:

• Headache
• Dizziness
• Temporary hair loss

Rare:

• Teratogenic effects (embryotoxicity and skeletal malformations) in pregnant animals
• Symptoms of overdose, which may include severe gastrointestinal disturbances

The clinically relevant drug interactions of Albendazole are briefly summarized here:

• Dexamethasone Interaction:

When coadministered with each dose of albendazole (15 mg/kg/day) in 8 neurocysticercosis patients, 8 mg of dexamethasone led to approximately 56% higher steady-state trough concentrations of albendazole sulfoxide.

• Praziquantel Interaction:

When given to healthy subjects (n = 10) in the fed state, praziquantel (40 mg/kg) caused an increase of around 50% in the mean maximum plasma concentration and area under the curve of albendazole sulfoxide, compared to a separate group of subjects (n = 6) who were given albendazole alone. However, the mean Tmax and mean plasma elimination half-life of albendazole sulfoxide remained unchanged. The pharmacokinetics of praziquantel remained the same when it was coadministered with albendazole (400 mg).

• Cimetidine Interaction:

When compared to albendazole (20 mg/kg/day) alone (n = 12), treatment with cimetidine (10 mg/kg/day) increased albendazole sulfoxide concentrations in bile and cystic fluid by approximately 2-fold in hydatid cyst patients (n = 7). However, albendazole sulfoxide plasma concentrations remained unchanged 4 hours after dosing.

• Theophylline Interaction:

The pharmacokinetics of theophylline (aminophylline 5.8 mg/kg infused over 20 minutes) remained unchanged following a single oral dose of albendazole (400 mg) in 6 healthy subjects.

The following are the side effects involving Albendazole:

• Headache
• Dizziness
• Nausea
• Vomiting
• Stomach and abdominal pain
• Temporary hair loss

The use of Albendazole should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category C

It has been found that Albendazole can cause harm to the fetus of pregnant rats and rabbits, leading to skeletal malformations and embryotoxicity. The teratogenic effects were observed in rats at oral doses of 10 and 30 mg/kg/day during gestation days 6 to 15, and in rabbits at an oral dose of 30 mg/kg/day administered during gestation days 7 to 19. In the rabbit study, maternal toxicity was noted, with a 33% mortality rate at the 30 mg/kg/day dose. However, no such effects were observed in mice at oral doses up to 30 mg/kg/day when administered during gestation days 6 to 15.

There are no sufficient and well-controlled studies on the administration of Albendazole in pregnant women. Hence, it is recommended to use Albendazole during pregnancy only if the benefits outweigh the potential risk to the fetus. Caution and careful evaluation of the situation are essential in such cases.

Lactation:

Albendazole is excreted in animal milk, but it is currently unknown whether it is excreted in human milk. Given that many drugs are excreted in human milk, caution should be exercised when administering albendazole to a nursing woman.

Pediatric:

Experience with children under the age of 6 years is limited. While hydatid disease infection in infants and young children is uncommon, no issues have been encountered in those treated for it. On the other hand, neurocysticercosis infection is more frequently encountered in pediatric patients. However, in five published studies involving pediatric patients as young as 1 year old, no significant problems were reported, and the treatment's efficacy appeared similar to that observed in the adult population.

Geriatric Use:

Limited experience exists for patients aged 65 years or older. The number of patients treated for hydatid disease or neurocysticercosis in this age group is also limited. However, no issues specific to the older population have been observed during the treatment.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Albendazole.

Significant toxicity and mortality were observed in male and female mice when administered doses surpassing 5,000 mg/kg. Similarly, in rats, toxic effects were seen at estimated doses ranging from 1,300 to 2,400 mg/kg. In hamsters, doses exceeding 10,000 mg/kg resulted in notable toxicity, while in rabbits, estimated doses between 500 and 1,250 mg/kg led to adverse effects.

The animals exhibited symptoms in a dose-response relationship, including diarrhoea, vomiting, tachycardia, and respiratory distress.

A single case of overdosage was reported in a patient who ingested at least 16 grams of Albendazole over a 12-hour period. Fortunately, no adverse effects were reported in this instance. In case of overdosage, it is advisable to administer symptomatic therapy and provide general supportive measures.

Pharmacodynamics:

Albendazole is a broad-spectrum anthelmintic that primarily acts by inhibiting tubulin polymerization. This action leads to the loss of cytoplasmic microtubules.

Pharmacokinetics:

Absorption and Metabolism

Albendazole's Poor Absorption: Due to its low aqueous solubility, albendazole is poorly absorbed from the gastrointestinal tract. Plasma concentrations of albendazole are minimal or undetectable as it quickly converts to its primary metabolite, albendazole sulfoxide, before entering the systemic circulation.

Enhanced Oral Bioavailability with Fatty Meal: Co-administration of albendazole with a fatty meal (approximately 40g fat) enhances oral bioavailability. This results in higher plasma concentrations of albendazole sulfoxide (up to 5-fold on average) compared to the fasted state.

Time to Reach Maximal Plasma Concentrations: Following oral dosing of albendazole (400mg) with a fatty meal, maximal plasma concentrations of albendazole sulfoxide are typically achieved 2 to 5 hours after dosing, with an average concentration of 1.31 mcg/mL (range 0.46 to 1.58 mcg/mL) in 6 hydatid disease patients.

Dose-Proportional Increase in Plasma Concentrations: Over the therapeutic dose range, plasma concentrations of albendazole sulfoxide increase in a dose-proportional manner when administered with a fatty meal (fat content 43.1g).

Apparent Terminal Elimination Half-Life: The mean apparent terminal elimination half-life of albendazole sulfoxide ranges from 8 to 12 hours in normal subjects, as well as in hydatid and neurocysticercosis patients.

Possible Induction of Metabolism: After 4 weeks of treatment with albendazole (200mg three times daily), patients' plasma concentrations of albendazole sulfoxide were about 20% lower than during the first half of the treatment, suggesting that albendazole may induce its own metabolism.

Distribution

Widespread Distribution: Albendazole sulfoxide is widely distributed throughout the body, with 70% of it bound to plasma protein. It has been detected in various tissues and fluids, including urine, bile, liver, cyst wall, cyst fluid, and cerebral spinal fluid (CSF).

Albendazole sulfoxide was found to have higher concentrations in plasma than in cyst fluid and CSF,

with concentrations being 3-10 times and 2-4 times higher, respectively. Limited in vitro and clinical data suggest that albendazole sulfoxide may be eliminated from cysts at a slower rate than from plasma.

Metabolism and Excretion

Liver Metabolism: Albendazole is rapidly converted in the liver to its primary metabolite, albendazole sulfoxide, which is further metabolized to albendazole sulfone and other oxidative metabolites detected in human urine.

Minimal Urinary Excretion: Only a small fraction of albendazole sulfoxide (less than 1% of the dose) is eliminated in the urine.

Biliary Elimination: Biliary elimination likely contributes to the elimination of albendazole sulfoxide, as evidenced by biliary concentrations similar to those in plasma.

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