Albendazole

P02C - Antinematodal agents ATC P02CA03 Small molecule approved 1996 Oral Prodrug Natural product

Active form: Albendazole Oxide.

JFDA label: Cystazole Tablet

Mechanism of Action

Inhibitor of Tubulin — Tubulin inhibitor

Target	Action	Gene / class
Tubulin efficacy	INHIBITOR

Indications

Approved

Hydatid disease
Neurocysticercosis

Off-label

Microsporidiosis in HIV-infected patients (adolescents and adults)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Helminths

Organism	Activity	MIC
Taenia solium	Active	—

Contraindications

Source: Lexicomp

Hypersensitivity to albendazole, benzimidazoles, or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (5)

Very Common dizziness · Headache · Increased intracranial pressure · meningism · vertigo

Hepatobiliary disorders (1)

Very Common Increased liver enzymes (hydatid: 16%; neurocysticercosis: 1% to 10%:

Skin and subcutaneous tissue disorders (1)

Very Common Alopecia, nausea and vomiting

General disorders and administration site conditions (1)

Very Common Fever

Dosing

Source: Lexicomp

Neurocysticercosis: Oral: ≥60 kg: 800 mg/day in 2 divided doses for 8 to 30 days Note: Give concurrent anticonvulsant and corticosteroid therapy. Hydatid: Oral: ≥60 kg: 800 mg/day in 2 divided doses Note: Administer dose for three 28-day cycles with a 14-day drug-free interval in between each cycle. Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm) (off-label use): Oral: 400 mg as a single dose (Parasitic Infections 2013) Clonorchis sinensis (Chinese liver fluke) or Opisthorchis viverrini (Southeast Asian liver fluke) (off-label use): Oral: 10 mg/kg/day for 7 days (Parasitic Infections 2013) Cutaneous larva migrans (off-label use): Oral: 400 mg once daily for 3 days (Parasitic Infections 2013) Cysticercus (off-label use): Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 8 to 30 days; may be repeated as necessary (Parasitic Infections 2013) Echinococcus granulosus (tapeworm) (off-label use): Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 1 to 6 months (Parasitic Infections 2013) Enterobius vermicularis (pinworm) (off-label use): Oral: 400 mg as a single dose; repeat in 2 weeks (Parasitic Infections 2013) Giardia duodenalis (giardiasis) (off-label use): Oral: 400 mg once daily for 5 days (Parasitic Infections 2013) Gnathostoma spinigerum (off-label use): Oral: 800 mg/day in 2 divided doses for 21 days (Parasitic Infections 2013) Gongylonemiasis (off-label use): Oral: 400 mg once daily for 3 days (Parasitic Infections 2013) Microsporidiosis: Immunocompetent patients: Disseminated (off-label use): 800 mg/day in 2 divided doses (Parasitic Infections 2013) Intestinal (E. intestinalis) (off-label use): 800 mg/day in 2 divided doses for 21 days (Parasitic Infections 2013) Ocular (off-label use): 800 mg/day in 2 divided doses, in combination with topical fumagillin (Parasitic Infections 2013) Immunocompromised (HIV-positive) patients Disseminated or intestinal infection (other than Enterocytozoon bieneusi or V. corneae) (off-label use): 800 mg/day in 2 divided doses; continue until CD4 count >200 cells/mm3 for >6 months after initiation of antiretroviral therapy (DHHS [OI Adults 2015]) Ocular (off-label use): 800 mg/day in 2 divided doses, 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 (DHHS [OI Adults 2015]) Oesophagostomum bifurcum (off-label use): Oral: 400 mg as a single dose (Ziem 2004) Trichinella spiralis (Trichinellosis) (off-label use): Oral: 800 mg/day in 2 divided doses for 8 to 14 days plus corticosteroids for severe symptoms (Parasitic Infections 2013) Visceral larva migrans (toxocariasis) (off-label use): Oral: 800 mg/day in 2 divided doses for 5 days (Parasitic Infections 2013)

(For additional information see "Albendazole: Pediatric drug information") Neurocysticercosis: Children and Adolescents: Oral: Refer to adult dosing. Hydatid: Children and Adolescents: Oral: Refer to adult dosing. Off-label uses: Cysticercus (off-label use): Pediatric: Oral: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses for 8 to 30 days; may be repeated as necessary (Parasitic Infections 2013) Giardia duodenalis (giardiasis) (off-label use): Children and Adolescents: Oral: 10 mg/kg/day for 5 days (Yereli 2004) Microsporidiosis (other than Enterocytozoon bieneuesi or V. corneae), disseminated or intestinal infection, HIV-positive (off-label use): Infants, Children, and Adolescents: 15 mg/kg/day (maximum: 800 mg/day) in 2 divided doses continued until immune reconstitution after cART initiation (DHHS [OI Children] 2013) Microsporidiosis, intestinal infection (immunocompetent) (off-label use): Infants ≥6 months and Children: 15 mg/kg/day in 2 divided doses for 7 days (Tremoulet 2004) Additional pediatric off-label uses: Refer to adult dosing: Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), Clonorchis sinensis (Chinese liver fluke), cutaneous larva migrans, Echinococcus granulosus (tapeworm), Enterobius vermicularis (pinworm), Gnathostoma spinigerum, gongylonemiasis, Necator americanus (hookworm), Oesophagostomum bifurcum, Opisthorchis viverrini (Southeast Asian liver fluke), Trichinella spiralis (Trichinellosis), visceral larva migrans (toxocariasis)

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, the need for adjustment not likely since albendazole is primarily eliminated by hepatic metabolism.

There are no dosage adjustments provided in manufacturer's labeling. However, patients with underlying liver disease may be more at risk for adverse effects.

Warnings & Precautions

Source: Lexicomp

Bone marrow suppression

Agranulocytosis, aplastic anemia, granulocytopenia, leukopenia, and pancytopenia have occurred leading to fatalities (rare); use with caution in patients with hepatic impairment (more susceptible to hematologic toxicity). Discontinue therapy in all patients who develop clinically significant decreases in blood cell counts.

Transaminase elevations

Reversible elevations in hepatic enzymes have been reported. Patients with abnormal LFTs and hepatic echinococcosis are at an increased risk of hepatotoxicity. Discontinue therapy if LFT elevations are >2 times the upper limit of normal; may consider restarting treatment (with frequent monitoring of LFTs) when hepatic enzymes return to pretreatment values. Discontinue therapy if hepatic enzymes are significantly increased. Disease-related concerns:

Neurocysticercosis

Appropriate use: Corticosteroids should be administered before or upon initiation of albendazole therapy to minimize inflammatory reactions and prevent increased intracranial pressure. Anticonvulsant therapy should be used concurrently to prevent seizures. If retinal lesions exist, weigh risk of further retinal damage due to albendazole-induced inflammatory changes to the retinal lesion vs benefit of disease treatment.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal reproduction studies. Albendazole should not be used during pregnancy, if at all possible. The manufacturer recommends a pregnancy test prior to therapy in women of reproductive potential. Women should be advised to avoid pregnancy during and for at least 1 month following therapy. Discontinue if pregnancy occurs during treatment.

Lactation

Albendazole excretion into breast milk was studied following a single oral 400 mg dose in breast-feeding women 2 weeks to 6 months postpartum (n=33). Mean albendazole concentrations 6 hours after the dose were 63.7 ± 11.9 ng/mL (maternal serum) and 31.9 ± 9.2 ng/mL (milk). An active and inactive metabolite was also detected in breast milk (Abdel-tawab, 2009). The manufacturer recommends that caution be exercised when administering albendazole to nursing women.

Monitoring

Clinical pearl	LFTs and CBC with differential at start of each 28-day cycle and every 2 weeks during therapy (more frequent monitoring for patients with liver disease); ophthalmic exam for retinal lesions (patients with neurocysticercosis); pregnancy test

Chemistry & Properties

Formula	C12H15N3O2S
Molecular weight	265.34 g/mol
IUPAC name	methyl N-(6-propylsulfanyl-1H-benzimidazol-2-yl)carbamate
CAS	54965-21-8
PubChem CID	2082
InChIKey	`HXHWSAZORRCQMX-UHFFFAOYSA-N`
logP	3.24 (XLogP 2.9)
Polar surface area	67.01 Å²
H-bond acceptors / donors	4 / 2
Drug-likeness (QED)	0.83
Lipinski violations	0

SMILES

CCCSc1ccc2[nH]c(NC(=O)OC)nc2c1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.844 h
Volume of distribution	0.849 L/kg
Protein binding	85.4%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)BCRP (Substrate)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (96, DDInter)

Interacting drug	Severity	Management
Cladribine	major
Clozapine	major
Abametapir (topical)	moderate
Alemtuzumab	moderate
Amprenavir	moderate
Anagrelide	moderate
Apalutamide	moderate
Aprepitant	moderate
Bendamustine	moderate
Bexarotene	moderate
Binimetinib	moderate
Boceprevir	moderate
Bosentan	moderate
Brigatinib	moderate
Carbamazepine	moderate
Cenobamate	moderate
Cobicistat	moderate
Conivaptan	moderate
Dabrafenib	moderate
Darunavir	moderate
Dasatinib	moderate
Deferasirox	moderate
Diltiazem	moderate
Dronedarone	moderate
Duvelisib	moderate
Echinacea	moderate
Efavirenz	moderate
Entrectinib	moderate
Enzalutamide	moderate
Etravirine	moderate
Fedratinib	moderate
Fluvoxamine	moderate
Fosamprenavir	moderate
Fosaprepitant	moderate
Fosnetupitant	moderate
Fosphenytoin	moderate
Fostamatinib	moderate
Ganciclovir	moderate
Grepafloxacin	moderate
Idelalisib	moderate

Showing 40 of 96.

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Cystazole Tablet	Tablet 200 mg	2 tab pack varies	Jordan Sweden Medical & Sterilization Co.	0.300
Cystazole Tablet	Tablet 200 mg	6 tab pack varies	Jordan Sweden Medical & Sterilization Co.	0.850
Cystazole Tablet	Tablet 200 mg	30 tab pack varies	Jordan Sweden Medical & Sterilization Co.	3.960
Cystazole Tablet	Tablet 200 mg	600 tab pack varies	Jordan Sweden Medical & Sterilization Co.	71.360