albendazole albendazole albendazole is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. it is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuriasis, strongyloidiasis, taeniasis, clonorchiasis, opisthorchiasis, cutaneous larva migrans, giardiasis, and gnathostomiasis, among other diseases. albendazoleclinical datatrade namesalbenza, valbazen, zentel, othersahfs/drugs.commonographmedlineplusa610019license data us dailymed: albendazole pregnancycategory au: d routes ofadministrationby mouthatc codep02ca03 (who) qp52ac11 (who)legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only (for humans; veterinary suspension and paste are both otc) pharmacokinetic databioavailability<5%protein binding70%metabolismhepaticelimination half-life8-12 hoursexcretionbile (humans)urine (ruminants)identifiers iupac name methyl carbamate cas number54965-21-8 ypubchem cid2082drugbankdb00518 ychemspider1998 yuniif4216019lnkeggd00134 ychebichebi:16664 ychemblchembl1483 yniaid chemdb007895comptox dashboard (epa)dtxsid0022563 echa infocard100.053.995 chemical and physical dataformulac12h15n3o2smolar mass265.33 g·mol−13d model (jsmol)interactive imagemelting point208 to 210 °c (406 to 410 °f) smiles cccsc2ccc1nc(nc(=o)oc)c1c2 inchi inchi=1s/c12h15n3o2s/c1-3-6-18-8-4-5-9-10(7-8)14-11(13-9)15-12(16)17-2/h4-5,7h,3,6h2,1-2h3,(h2,13,14,15,16) ykey:hxhwsazorrcqmx-uhfffaoysa-n y (verify) common side effects include nausea, abdominal pain, and headache. rare but potentially serious side effects include bone marrow suppression which usually improves on discontinuing the medication. liver inflammation has been reported and those with prior liver problems are at greater risk. it is pregnancy category d in australia, meaning it may cause harm if taken by pregnant women. albendazole was developed in 1975. it is on the world health organization's list of essential medicines. medical uses albendazole is an effective treatment for: flatworms fasciolosis cestodes (tapeworms), as an alternative to praziquantel or niclosamide for adult beef tapewormss and as an alternative to praziquantel for pork tapeworms. it is also given for infections by t. crassiceps. though praziquantel is often better at treating tapeworm infections, albendazole is used more often in endemic countries due to being cheaper and having a broader spectrum. cysticercosis (especially neurocysticercosis), which is caused by the larval form of the pork tapeworm (i.e. albendazole is the drug of choice for larval pork tapeworms, but not adult pork tapeworms). old cysts are not affected. echinococcosis of the liver, lung, and peritoneum (caused by the larval form of the dog tapeworm, or of the alveoli (caused by e. multilocularis) when surgical excision is not possible. alveolar and cystic echinococcosis may require lifelong treatment with albendazole, which only prevents the parasites from growing and reproducing rather than killing them. nematodes ascariasis, which can be cured with a single dose of albendazole. baylisascariasis, caused by the raccoon roundworm. albendazole can achieve good results (95%-100% efficacy after a 10-day course of treatment) if treatment is initiated within 72 hours of ingestion of the egg-containing raccoon feces. corticosteroids are sometimes added in cases of eye and cns infections. pinworm infection filariasis; since albendazole's disintegration of the microfilariae ("pre-larva") can cause an allergic reaction, antihistamines or corticosteroids are sometimes added to treatment. in cases of lymphatic filariasis (elephantiasis) caused by wuchereria bancrofti or brugia malayi, albendazole is sometimes given as an adjunct to ivermectin or diethylcarbamazine in order to suppress microfilaremia. it can also be given for loa loa filariasis as an adjunct or replacement to diethylcarbamazine. albendazole has an embryotoxic effect on loa loa adults and thus slowly reduces microfilaremia. gnathostomiasis when caused by gnathostoma spinigerum. albendazole has a similar effectiveness to ivermectin in these cases, though it needs to be given for 21 days rather than the 2 days needed for ivermectin. gongylonemiasis hookworm infections, including cutaneous larva migrans caused by hookworms of genus ancylostoma. a single dose of albendazole is sufficient to treat intestinal infestations by a. duodenale or necator americanus. intestinal capillariasis, as an alternative to mebendazole mansonelliasis when caused by mansonella perstans. albendazole is effective against adult worms but not against the immature microfilariae. oesophagostomumiasis, when caused by oesophagostomum bifurcum strongyloidiasis, as an alternative to ivermectin or thiabendazole. albendazole can be given with diethylcarbamazine to lower microfilaremia levels. toxocariasis, also called "visceral larva migrans", when caused by the dog roundworm toxocara canis or cat roundworm t. catis. corticosteroids can be added in severe cases, and surgery might be required to repair secondary damage. trichinosis, when caused by trichinella spiralis or t. pseudospiralis. albendazole has a similar efficacy to thiabendazole, but fewer side effects. it works best when given early, acting on the adult worms in the intestine before they generate larva that can penetrate the muscle and cause a more widespread infection. corticosteroids are sometimes added on to prevent inflammation caused by dying larva. trichostrongyliasis, as an alternative to pyrantel pamoate. a single dose is sufficient for treatment. trichuriasis (whipworm infection), sometimes considered as an alternative to mebendazole and sometimes considered to be the drug of choice. only a single dose of albendazole is needed. it can also be given with ivermectin. giardiasis, as an alternative or adjunct to metronidazole, especially in children microsporidiosis, including ocular microsporidiosis caused by encephalitozoon hellem or e. cuniculi, when combined with topical fumagillin granulomatous amoebic encephalitis, when caused by the amoeba balamuthia mandrillaris, in combination with miltefosine and fluconazole arthropods crusted scabies, when combined with topical crotamiton and salicylic acid head lice infestation, though ivermectin is much better intestinal myiasis though albendazole is effective in treating many diseases, it is only fda-approved for treating hydatid disease caused by dog tapeworm larvae and neurocysticercosis caused by pork tapeworm larvae. pregnancy albendazole is a pregnancy class d drug in australia. it is contraindicated in the first trimester of pregnancy, and should be avoided up to one month before conception. while studies in pregnant rats and rabbits have shown albendazole to be teratogenic, albendazole has been found to be safe in humans during the second and third trimesters. it can, however, possibly cause infantile eczema when given during pregnancy. in pregnant dogs, albendazole use has led to puppies with reduced weight and with cleft palates. birds have lower rates of laying eggs and hatching when given albendazole. albendazole sulfoxide is secreted into breast milk at around 1.5% of the maternal dose, though oral absorption is poor enough that it is unlikely to affect nursing infants. contraindications hypersensitivity to the benzimidazole class of compounds contraindicates its use. side effects close-up of a pork tapeworm cyst. destruction of these cysts can cause inflammation. the most common side effects of albendazole are experienced by over 10% of people and include headache and abnormal liver function. elevation of liver enzymes occurs in 16% of patients receiving treatment specifically for hydatid disease and goes away when treatment ends. liver enzymes usually increase to two to four times the normal levels (a mild to moderate increase). an estimated 1–10% of people experience abdominal pain, nausea or vomiting, dizziness or vertigo, increased intracranial pressure, meningeal signs, temporary hair loss, and fever. the headache, nausea, and vomiting are thought to be caused by the sudden destruction of cysticerci (tapeworm larvae), which causes acute inflammation. fewer than 1% of people get hypersensitivity reactions such as rashes and hives, leukopenias (drop in white blood cell levels) such as agranulocytosis and granulocytopenia, thrombocytopenia (reduced platelet count), pancytopenia (drop in white blood cells, red blood cells, and platelets), hepatitis, acute liver failure, acute kidney injury, irreversible bone marrow suppression, and aplastic anemia. side effects can be different when treating for hydatid disease versus neurocysticercosis: for example, those being treated for the former are more likely to experience elevated liver enzymes and abdominal pain, while those being treated for the latter are more likely to experience headache. treating hydatid disease can also unmask undiagnosed neurocysticercosis. people receiving albendazole for the treatment of neurocysticercosis can have neurological side effects such as seizures, increased intracranial pressure, and focal signs caused by the inflammatory reaction that occurs when parasites in the brain are killed. steroids and anticonvulsants are often given with albendazole when treating neurocysticercosis to avoid these effects. those being treated for retinal neurocysticercosis can face retinal damage if they are not first checked for ocular cysticeri, since changes to existing lesions in the eye by albendazole can cause permanent blindness. overdose because of its low solubility, albendazole often cannot be absorbed in high enough quantities to be toxic. the oral ld50 of albendazole in rats was found to be 2,500 mg/kg. it takes 20 times the normal dose to kill a sheep, and 30 times the normal dose to kill cattle. overdose affects the liver, testicles, and gi tract the most. it can manifest with lethargy, loss of appetite, vomiting, diarrhea, intestinal cramps, dizziness, convulsions, and sleepiness. there is no specified antidote. interactions the antiepileptics carbamazepine, phenytoin, and phenobarbital lower the plasma concentration and half-life of albendazole sulfoxide's r(+) enantiomer. antiepileptics and pharmacokinetics of albendazole sulfoxide drugchange in aucchange in cmax carbamazepine49% decrease50–63% decrease phenobarbitol61% decrease50–63% decrease phenytoin66% decrease50–63% decrease the antacid cimetidine heightens serum albendazole concentrations, increases the half-life of albendazole, and doubles albendazole sulfoxide levels in bile. it was originally thought to work by increasing albendazole bioavailability directly; however, it is now known that cimetidine inhibits the breakdown of albendazole sulfoxide by interfering with cyp3a4. the half-life of albendazole sulfoxide thus increases from 7.4 hours to 19 hours. this might be a helpful interaction on more severe cases, because it boosts the potency of albendazole. paradoxically, cimetidine also inhibits the absorption of albendazole by reducing gastric acidity. several other interactions exist. corticosteroids increase the steady-state plasma concentration of albendazole sulfoxide; dexamethasone, for example, can increase the concentration by 56% by inhibiting the elimination of albendazole sulfoxide. the anti-parasitic praziquantel increases the maximum plasma concentration of albendazole sulfoxide by 50%, and the anti-parasitic levamisole increases the auc (total drug exposure) by 75%. grapefruit inhibits the metabolism of albendazole within the intestinal mucosa. finally, long-term administration of the antiretroviral ritonavir, which works as a cyp3a4 inhibitor, decreases the maximum concentration of albendazole in the plasma as well as the auc. pharmacology a microtubule is composed of polymers of α- and β-tubulin. mechanism of action as a vermicide, albendazole causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals). albendazole leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. albendazole also prevents the formation of spindle fibers needed for cell division, which in turn blocks egg production and development; existing eggs are prevented from hatching. cell motility, maintenance of cell shape, and intracellular transport are also disrupted. at higher concentrations, it disrupts the helminths' metabolic pathways by inhibiting metabolic enzymes such as malate dehydrogenase and fumarate reductase, with inhibition of the latter leading to less energy produced by the krebs cycle. due to diminished atp production, the parasite is immobilized and eventually dies. some parasites have evolved some resistance to albendazole by having a different set of acids constituting β-tubulin, decreasing the binding affinity of albendazole. some parasites (especially filarial nematodes) live in symbiosis with wolbachia, a type of intracellular parasite bacteria. in such cases the wolbachia are necessary to the survival of the parasitic worms. elimination of wolbachia from these filarial nematodes generally results in either death or sterility of the host nematode. pharmacokinetics oral absorption of albendazole varies among species, with 1–5% of the drug being successfully absorbed in humans, 20–30% in rats, and 50% in cattle. the absorption also largely depends on gastric ph. people have varying gastric phs on empty stomachs, and thus absorption from one person to another can vary wildly when taken without food. generally, the absorption in the gi tract is poor due to albendazole's low solubility in water. it is, however, better absorbed than other benzimidazole carbamates. food stimulates gastric acid secretion, lowering the ph and making albendazole more soluble and thus more easily absorbed. oral absorption is especially increased with a fatty meal, as albendazole dissolves better in lipids, allowing it to cross the lipid barrier created by the mucus surface of the gi tract. to target intestinal parasites, albendazole is taken on an empty stomach to stay within the gut. absorption is also affected by how much of the albendazole is degraded within the small intestine by metabolic enzymes in the villi. general metabolism of albendazole and its sulfoxides. the pharmacokinetics of albendazole differ slightly between men and women: women have a lower oral clearance and volume of distribution, while men have a lower serum peak concentration. albendazole undergoes very fast first-pass metabolism in all species, such that the