Albendazole

Usage

Albendazole is prescribed for the treatment of a variety of parasitic worm infestations, including:

• Nematode infections: Ascariasis (roundworm), Trichuriasis (whipworm), Hookworm infection, Enterobiasis (pinworm), Strongyloidiasis, Cutaneous larva migrans (creeping eruption), Visceral larva migrans, Trichostrongyliasis, Capillariasis.
• Cestode infections: Hydatid disease (caused by Echinococcus species), Neurocysticercosis (caused by the larval stage of the pork tapeworm Taenia solium).
• Protozoal infections: Giardiasis (caused by Giardia lamblia).

Pharmacological Classification: Anthelmintic, Antiprotozoal

Mechanism of Action: Albendazole inhibits tubulin polymerization in parasitic worms, disrupting microtubule formation and function. This interferes with glucose uptake, leading to glycogen depletion and ultimately the death of the parasite.

Alternate Names

Albendazole is also known as Albendazolum. There are numerous brand names under which albendazole is marketed, including Albenza, Eskazole, and Zentel.

How It Works

Pharmacodynamics: Albendazole’s primary effect is on the parasite’s cytoskeleton. By inhibiting tubulin polymerization, it disrupts essential cellular processes, leading to parasite immobilization and death.

Pharmacokinetics:

• Absorption: Albendazole has poor oral bioavailability, which is significantly increased when taken with a fatty meal.
• Metabolism: It is rapidly metabolized in the liver to its primary active metabolite, albendazole sulfoxide.
• Elimination: Albendazole sulfoxide is primarily eliminated in the bile and feces, with minimal renal excretion. The plasma half-life of albendazole sulfoxide is approximately 8.5 hours.

Mode of Action: Albendazole selectively binds to β-tubulin in parasitic worms, preventing the formation of microtubules. This disrupts several crucial functions, including glucose uptake, intracellular transport, and cell division, eventually leading to the parasite’s death.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Albendazole’s mechanism of action primarily involves the inhibition of tubulin polymerization. It does not directly interact with receptors, neurotransmitters, or inhibit enzymes other than those involved in tubulin synthesis.

Elimination Pathways: Primarily biliary and fecal excretion, with minimal renal excretion. Albendazole undergoes extensive first-pass metabolism in the liver.

Dosage

Standard Dosage

Adults:

For most indications, the standard adult dose is 400 mg orally once or twice daily, depending on the specific infection. It’s crucial to administer the medication with food, preferably a high-fat meal, to enhance absorption.

Children:

Pediatric dosing is typically based on weight: 15 mg/kg/day divided into two doses, with a maximum dose of 800 mg/day. Like adults, children should take albendazole with food. Safety and efficacy have not been established in children younger than one year for some indications.

Special Cases:

• Elderly Patients: Dosage adjustments are generally not necessary, but caution is advised in those with hepatic dysfunction.
• Patients with Renal Impairment: No dosage adjustment is needed.
• Patients with Hepatic Dysfunction: Careful monitoring is required. Dose reduction may be necessary.
• Patients with Comorbid Conditions: Exercise caution in patients with liver disease. No specific dosing adjustments for diabetes or cardiovascular disease are indicated.

Clinical Use Cases

Albendazole is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is in treating parasitic infections.

Dosage Adjustments

Dosage adjustments may be required based on the specific parasitic infection being treated, the patient’s weight, and the presence of hepatic impairment.

Side Effects

Common Side Effects:

• Headache
• Dizziness, Vertigo
• Nausea, Vomiting
• Abdominal pain
• Diarrhea
• Elevated liver enzymes
• Temporary hair loss (reversible alopecia)

Rare but Serious Side Effects:

• Leukopenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Pancytopenia (reduction of all blood cell types)
• Agranulocytosis
• Aplastic anemia
• Hepatic dysfunction (including hepatitis and liver failure)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Angioedema

Long-Term Effects: Chronic complications from prolonged albendazole use are rare. However, long-term monitoring of liver function may be necessary.

Adverse Drug Reactions (ADR): Serious ADRs requiring immediate intervention include severe allergic reactions (anaphylaxis, angioedema), bone marrow suppression (pancytopenia, agranulocytosis), and severe liver injury.

Contraindications

• Absolute Contraindications: Hypersensitivity to albendazole or other benzimidazole derivatives, pregnancy (first trimester).
• Relative Contraindications: Pre-existing liver disease, bone marrow suppression.

Drug Interactions

• CYP450 Interactions: Albendazole is metabolized by CYP3A4 and CYP1A2. Enzyme inducers (e.g., phenytoin, carbamazepine, rifampin) may decrease albendazole levels, while inhibitors (e.g., cimetidine, grapefruit juice, ketoconazole) may increase levels.
• Other Drug Interactions: Dexamethasone may increase albendazole sulfoxide levels. Praziquantel may also interact with albendazole.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (second and third trimesters). Contraindicated in the first trimester.
• Fetal Risks: Teratogenic in animal studies, especially during the first trimester.
• Breastfeeding: Limited data. Albendazole and its metabolites are excreted in breast milk, but at low levels. Use with caution. Consider the risks and benefits.

Drug Profile Summary

• Mechanism of Action: Inhibits tubulin polymerization in parasites, disrupting microtubule formation and function.
• Side Effects: Common: Headache, dizziness, GI upset. Serious: Bone marrow suppression, liver injury, allergic reactions.
• Contraindications: Hypersensitivity, first-trimester pregnancy.
• Drug Interactions: CYP3A4 and CYP1A2 inducers/inhibitors, dexamethasone, praziquantel.
• Pregnancy & Breastfeeding: Contraindicated in first trimester; use with caution during breastfeeding.
• Dosage: Variable, depending on the infection and patient characteristics. Consult specific guidelines.
• Monitoring Parameters: Complete blood count (CBC), liver function tests (LFTs).

Popular Combinations

Albendazole is sometimes used in combination with praziquantel and corticosteroids for the treatment of neurocysticercosis. This combination helps to manage the inflammatory response associated with parasite death in the brain.

Precautions

• Obtain a negative pregnancy test before initiating therapy in women of childbearing potential.
• Use effective contraception during treatment and for one month after the last dose.
• Monitor CBC and LFTs, especially during prolonged therapy or in patients with pre-existing liver disease.
• Be aware of the potential for neurological symptoms in patients with neurocysticercosis.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Albendazole?

A: Dosage varies depending on the indication. For many common helminth infections in adults and children over 2 years, a single dose of 400 mg is given. For hydatid disease, the dose is 400 mg twice daily for 28 days, followed by a 14-day drug-free interval, repeated for three cycles. For neurocysticercosis, the dose is 400 mg twice daily for 8-30 days. Pediatric doses are generally calculated as 15 mg/kg/day divided into two doses, not to exceed 800 mg/day.

Q2: What are the common side effects of Albendazole?

A: The most common side effects include headache, dizziness, nausea, vomiting, abdominal pain, and elevated liver enzymes.

Q3: What are the serious side effects of Albendazole?

A: Serious side effects, though rare, can include bone marrow suppression (leukopenia, pancytopenia), severe allergic reactions, and liver damage.

Q4: Can Albendazole be used during pregnancy?

A: Albendazole is contraindicated during the first trimester of pregnancy. It should be avoided in women of childbearing potential unless effective contraception is used. Use during the second and third trimesters should only occur if the benefits clearly outweigh the risks.

Q5: Can Albendazole be used during breastfeeding?

A: Limited data suggest that albendazole is present in breast milk at low concentrations. Use caution during breastfeeding and consider the potential risks and benefits for both mother and infant.

Q6: What are the drug interactions to be aware of with Albendazole?

A: Albendazole interacts with drugs that induce or inhibit CYP3A4 and CYP1A2 enzymes. Concomitant use of dexamethasone may increase albendazole sulfoxide levels. Praziquantel and cimetidine may also interact.

Q7: How is Albendazole administered?

A: Albendazole is administered orally, preferably with a fatty meal to enhance absorption. Tablets can be chewed or crushed if necessary. A suspension is also available for children and individuals who have difficulty swallowing tablets.

Q8: What should be monitored in patients taking Albendazole?

A: Complete blood counts (CBC) and liver function tests (LFTs) should be monitored periodically, especially during long-term therapy or in patients with pre-existing liver disease.

Q9: What is the mechanism of action of Albendazole?

A: Albendazole inhibits tubulin polymerization in parasites, leading to microtubular dysfunction, impaired glucose uptake, and ultimately parasite death.

Q10: Is there a risk of developing resistance to Albendazole?

A: While resistance to albendazole has been reported in some parasitic species in veterinary settings, it is less common in human infections. However, the possibility of resistance developing should be considered, particularly in cases of treatment failure.