Albenza

Antinematodal Agents

Administer with food, preferably a high-fat meal, to increase oral bioavailability.
Albendazole tablets may be chewed or crushed.

hepatic failure / Delayed / 0-1.0
renal failure (unspecified) / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 0-16.0
hepatitis / Delayed / 0-1.0
blurred vision / Early / Incidence not known

diarrhea / Early / Incidence not known
drowsiness / Early / Incidence not known
asthenia / Delayed / Incidence not known

Albenza

Rx

Oral broad-spectrum antihelmintic antiparasitic agent (benzimidazole class)
Used for hydatid cyst disease and neurocysticercosis; many off-label uses
Similar to mebendazole and thiabendazole but better tolerated

400 mg PO twice daily with meals for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles.

15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles.

15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles. Published data in pediatric patients for this indication are limited, particularly in infants and young children, in whom hydatid disease is uncommon.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 10 to 14 days with corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 10 to 14 days with corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 10 to 14 days combined with praziquantel and corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 10 to 14 days combined with praziquantel and corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 800 mg/day) PO in 2 divided doses for 7 to 14 days combined with corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 800 mg/day) PO in 2 divided doses for 7 to 14 days combined with corticosteroids. The FDA-approved maximum dosage is 800 mg/day for 8 to 30 days.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses combined with praziquantel and corticosteroids. Continue treatment for 2 to 12 months or until resolution of cystic lesions on neuroimaging studies.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses combined with praziquantel and corticosteroids. Continue treatment for 2 to 12 months or until resolution of cystic lesions on neuroimaging studies.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 14 days. Antiparasitic and corticosteroid therapy is recommended after shunt insertion to decrease subsequent shunt failure when surgical removal of isolated intraventricular cysts is not possible.

15 mg/kg/day (Max: 1,200 mg/day) PO in 2 divided doses for 14 days. Antiparasitic and corticosteroid therapy is recommended after shunt insertion to decrease subsequent shunt failure when surgical removal of isolated intraventricular cysts is not possible.

15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 8 to 30 days; can be repeated as necessary. Surgery is indicated for intraocular cysts; intraocular cysts should be removed before administration of antiparasitic treatment to avoid irreversible eye damage due to the inflammatory response.

15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 8 to 30 days; can be repeated as necessary. Surgery is indicated for intraocular cysts; intraocular cysts should be removed before administration of antiparasitic treatment to avoid irreversible eye damage due to the inflammatory response.

400 mg PO as a single dose.

400 mg PO as a single dose.

200 mg PO twice daily for 10 days.

200 mg PO twice daily for 10 days.

400 mg PO once daily for 3 days.

5 mg/kg/day PO for 3 days.

400 mg PO twice daily for 14 to 28 days.

7.5 mg/kg/dose (Max: 400 mg/dose) PO twice daily for 7 days.

400 mg PO twice daily until CD4 count is more than 200 cells/mm3 for at least 6 months after starting antiretroviral therapy.[34362]

400 mg PO twice daily until CD4 count is more than 200 cells/mm3 for at least 6 months after starting antiretroviral therapy.

7.5 mg/kg/dose (Max: 400 mg/dose) PO twice daily until immune reconstitution after starting antiretroviral therapy.

400 mg PO twice daily in combination with itraconazole until CD4 count is more than 200 cells/mm3 for at least 6 months after starting antiretroviral therapy.

400 mg PO twice daily in combination with itraconazole until CD4 count is more than 200 cells/mm3 for at least 6 months after starting antiretroviral therapy.

400 mg PO twice daily in combination with topical fumagillin bicylohexylammonium eye drops. Consider treatment discontinuation if signs and symptoms of the ocular infection resolve and the CD4 count is more than 200 cells/mm3.[34362]

400 mg PO twice daily in combination with topical fumagillin bicylohexylammonium eye drops. Consider treatment discontinuation if signs and symptoms of the ocular infection resolve and the CD4 count is more than 200 cells/mm3.

7.5 mg/kg/dose (Max: 400 mg/dose) PO twice daily in combination with topical fumagillin until immune reconstitution after starting antiretroviral therapy.

400 mg PO twice daily for 7 days.[64719]

400 mg PO twice daily for 7 days.[64719]

400 mg PO twice daily for 8 to 14 days.

400 mg PO twice daily for 8 to 14 days.

400 mg PO as a single dose.

400 mg PO as a single dose; repeat dose in 2 weeks.

400 mg PO as a single dose; repeat dose in 2 weeks.

200 to 400 mg PO as a single dose; repeat dose in 2 weeks.

400 mg PO as a single dose.

400 mg PO as a single dose.

400 mg PO once daily for 3 days.

400 mg PO once daily for 3 days.

400 mg PO once daily for 5 days.

10 mg/kg/dose (Max: 400 mg/dose) PO once daily for 5 days.

†Indicates off-label use

Patients with abnormal liver function tests prior to beginning albendazole therapy should be carefully evaluated. In patients with evidence of extrahepatic biliary obstruction, the systemic exposure of albendazole sulfoxide is increased and the elimination is prolonged.

The pharmacokinetics of albendazole in patients with renal impairment have not been studied; however, renal elimination of albendazole and albendazole sulfoxide is negligible and dosage adjustment in renal impairment is not expected to be necessary.

Carbamazepine: (Minor) Enzyme-inducing antiepileptic drugs, such as carbamazepine, appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
Cimetidine: (Moderate) Cimetidine administration with albendazole has been reported to increase albendazole bioavailability. Concentrations of albendazole sulfoxide were increased in bile and cystic fluid about 2 fold in patients with hydatid cyst disease treated with cimetidine 10 mg per kg per day concomitantly with albendazole compared to administration of albendazole alone. More data are needed to elucidate the clinical consequence of this interaction.
Dexamethasone: (Moderate) Monitor for an increase in albendazole-related adverse reactions if concomitant use with dexamethasone is necessary. Concomitant use increased the steady-state trough concentrations of albendazole sulfoxide by about 56%.
Food: (Moderate) Albendazole tablets should be administered with a fatty meal to increase bioavailability and ensure therapeutic efficacy.
Grapefruit juice: (Moderate) Grapefruit juice appears to increase the bioavailability of albendazole via reduction of CYP3A4-mediated metabolism in the intestinal mucosa. The AUC and Cmax of albendazole increased approximately 3-fold and the half-life was shortened by 46 percent when administered with grapefruit juice. The clinical consequence of the interaction is not clear, Patients should be advised to not significantly alter their intake of grapefruit juice during albendazole therapy.
Hydantoins: (Minor) Antiepileptic drugs (AEDs) are often administered concomitantly with albendazole for the treatment of neurocysticercosis. Hydantoins appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
Phenobarbital: (Minor) Phenobarbital appears to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. It is not clear if these pharmacokinetic interactions affect the therapeutic efficacy of albendazole in the treatment of neurocysticercosis. Monitor patient clinical response closely during treatment.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Phenobarbital appears to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. It is not clear if these pharmacokinetic interactions affect the therapeutic efficacy of albendazole in the treatment of neurocysticercosis. Monitor patient clinical response closely during treatment.
Praziquantel: (Moderate) The serum concentration of albendazole may be increased if coadministered with praziquantel. Use albendazole cautiously in combination with praziquantel.
Theophylline, Aminophylline: (Moderate) Albendazole has been shown to induce the hepatic CYP1A microsomal enzymes. It is possible that the prescription of albendazole may result in an increased clearance of theophylline via induction of CYP1A enzymes. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of theophylline, leading to an increase in serum theophylline concentrations. Theophylline serum concentrations and the patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy. (Moderate) Albendazole has been shown to induce the hepatic CYP1A microsomal enzymes. It is possible that the prescription of albendazole may result in an increased clearance of aminophylline via induction of CYP1A enzymes. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of aminophylline, leading to an increase in serum aminophylline concentrations. Aminophylline serum concentrations and the patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.

Albendazole/Albenza Oral Tab: 200mg

15 mg/kg/day PO or 800 mg/day PO for most indications; up to 3200 mg/day PO in HIV patients with microsporidiosis.

15 mg/kg/day PO or 800 mg/day PO for most indications.

15 mg/kg/day PO, not to exceed 800 mg/day PO.

15 mg/kg/day PO, not to exceed 800 mg/day PO.

Mechanism of Action: Benzimidazole antihelmintic agents inhibit the polymerization of tubulin and the microtubule-dependent uptake of glucose by binding free ß-tubulin. Albendazole selectively damages cytoplasmic microtubules in the absorptive and intestinal cells of nematodes but not of the host. This microtubular deterioration is irreversible and leads to disruption of absorptive and secretory functions of the cells, which are essential to the organism's survival. This disruption results in accumulation of secretory substances in the Golgi apparatus, decreased glucose uptake, and depleted endogenous glycogen stores in the helminth. Due to diminished energy production the parasite is immobilized and eventually dies. Albendazole is larvicidal in necatoriasis and ovicidal in ascariasis, ancylostomiasis, and trichuriasis. Resistance to albendazole has been documented in animals and is due to loss of affinity to tubulin binding sites.In general, the following organisms are susceptible to albendazole: Echinococcus granulosus (dog tapeworm), Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), Trichinella spiralis (pork worm), Trichuris trichiura (whipworm), Enterobius vermicularis (pinworm), Strongyloides stercoralis (threadworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm).

Albendazole is administered orally. In the treatment of hydatid disease, tissue concentrations of albendazole sulfoxide > 500 ng/mL are required for therapeutic efficacy. Albendazole sulfoxide is 70% protein bound and has a half life of approximately 8—12 hours. Concentrations in plasma are approximately 3-fold to 10-fold and 2-fold to 4-fold higher than those seen in cyst fluid and CSF, respectively. Albendazole is extensively metabolized by the liver to albendazole sulfoxide, the primary active metabolite.The primary elimination route is the bile. Renal elimination is negligible (< 1%).
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A
Albendazole induces cytochrome P450 1A enzymes and may induce its own metabolism. After 4 weeks of treatment with albendazole (200 mg 3 times daily), plasma concentrations were 20% lower than those observed in the first half of the treatment period in 12 patients.

The chewable tablets have been shown to be bioequivalent to the oral tablets. After oral administration, albendazole is poorly absorbed from the GI tract. To increase bioavailability, it is recommended to give albendazole with a high-fat meal; the absorption of albendazole increases between 5 to 6.5-fold compared to when given with a non-fatty meal. Grapefruit juice also increases albendazole's oral bioavailability. After oral administration, peak plasma concentrations are reached at approximately 4.5 hours (range, 2—10 hours) when given with a fatty meal compared with 3 hours (range, 1—5 hours) in the fasted state. After administration of albendazole (400 mg) regular tablets with a fatty meal, peak plasma concentrations of albendazole sulfoxide were on average 1310 ng/mL (range, 460—1580 ng/mL) in 6 patients with hydatid disease. Concentrations of albendazole sulfoxide appear to increase in a dose-proportional manner over the therapeutic range after administration with a high-fat meal. Average peak plasma concentrations of albendazole sulfoxide after administration of a 400-mg dose of chewable tablets were 804 ng/mL (range, 202—2244 ng/mL) and 218 ng/mL (range, 54—592 ng/mL) in the fed and fasted states, respectively. In the treatment of hydatid disease, tissue concentrations of albendazole sulfoxide > 500 ng/mL are required for therapeutic efficacy.

Advise pregnant women of the potential risk to the fetus with albendazole therapy. Based on findings from animal reproduction studies, albendazole may cause fetal harm when administered to a pregnant woman. However, available human data from a small number of case series and reports on the use of multiple-dose albendazole in the first trimester of pregnancy and several studies on single-dose albendazole use later in pregnancy have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes.[28046] The World Health Organization (WHO) supports the use of albendazole as antihelminthic therapy after the first trimester of pregnancy.[64428] Guidelines suggest deferring treatment for neurocysticercosis until after pregnancy unless intracranial pressure is elevated.[63735] In animal reproductive studies, oral administration of albendazole during the period of organogenesis caused embryotoxicity and skeletal malformations at doses 0.1 to 0.6 times the maximum recommended human dose (MRHD) based on body surface area and was associated with maternal toxicity at doses 0.6 times the MRHD based on body surface area.[28046]

Albendazole may be associated with reproductive risk. Obtain pregnancy testing before prescribing albendazole to females of reproductive potential. Discuss contraception requirements with the patient. Advise women of reproductive potential to use effective birth control during albendazole treatment and for 3 days after the final dose.[28046]