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Thursday, 4 October 2012

Albendazole

Class: Anthelmintics
VA Class: AP200
Chemical Name: [5-(Propylthio)-1H-benzimidazol-2-yl]-carbamic acid methyl ester
Molecular Formula: C₁₂H₁₅N₃O₂S
CAS Number: 54965-21-8
Brands: Albenza

Introduction

Anthelmintic agent; benzimidazole derivative.¹ ⁴

Uses for Albendazole

Neurocysticercosis

Treatment of parenchymal neurocysticercosis resulting from active lesions caused by Cysticercus cellulosae, the larval form of Taenia solium (pork tapeworm).¹ ⁵ ⁷ ⁸ ¹³

Albendazole and praziquantel are drugs of choice, but treatment of neurocysticercosis is controversial.⁸ ¹³ (See Precautions Related to Treatment of Neurocysticercosis under Cautions.)

Corticosteroids usually used concomitantly to reduce frequency and severity of adverse nervous system effects (CSF reaction syndrome).¹ ⁵ ⁷ ⁸ ¹³ Anticonvulsant therapy also may be necessary.¹ ⁵ ⁷ ⁸ ¹³

If retinal lesions are present, weigh risk versus benefit.¹ ⁵ ⁸ Ocular and spinal cysts generally are not treated with anthelmintic drugs since irreparable damage may occur, even with concomitant corticosteroids.⁸ ¹³

Hydatid Disease

Treatment of cystic hydatid disease (unilocular hydatid disease) of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm (Echinococcus granulosus).¹ ³ ⁵ ⁷ ⁸ ¹³

Surgery is the treatment of choice when medically feasible;¹ ³ ⁵ ⁷ ⁸ ¹¹ ¹² ¹³ perioperative use of an anthelmintic may be indicated to minimize the risk of intraoperative dissemination of daughter cysts.⁷ ⁸ ¹¹ Albendazole is drug of choice when an antihelmintic is indicated.⁷ ⁸ ¹¹ ¹²

Has been used for treatment of alveolar hydatid disease† caused by Echinococcus multilocularis.³ ⁵ ⁷ ⁸ ¹² ¹³ Surgical excision of the larval mass is the recommended and only reliable treatment.⁸ ¹³ Although efficacy has not been definitely established, continuous albendazole (or mebendazole) therapy has been associated with clinical improvement in some nonresectable cases.¹³

Ascariasis

Treatment of ascariasis† caused by Ascaris lumbricoides.⁸ ¹³ Albendazole, mebendazole, and ivermectin are drugs of choice.⁸ ¹³

Baylisascariasis

Has been used for treatment of baylisascariasis† caused by Baylisascaris procyonis.⁸ ¹³ ¹⁸

Although no drug has been proven effective,⁸ ¹⁸ immediate albendazole treatment (within 1–3 days of infection) is recommended in cases of probable infection, including known exposures such as ingestion of raccoon stool or contaminated soil.⁸ ¹⁸ Ivermectin, mebendazole, thiabendazole, and levamisole (not commercially available in the US) are alternatives.⁸ Concomitant corticosteroid therapy may be helpful, especially in ocular and CNS infections.⁸

Additional information on baylisascariasis can be obtained at

Enterobiasis

Treatment of enterobiasis† caused by Enterobius vermicularis (pinworm).⁸ ¹³ Albendazole, mebendazole, and pyrantel pamoate are drugs of choice.⁸ ¹³

Filariasis

Treatment of filariasis† caused by Mansonella perstans.⁸ Albendazole and mebendazole are drugs of choice.⁸ Antihistamines or corticosteroids also may be indicated to decrease allergic reactions secondary to disintegration of microfilariae following treatment.⁸

Treatment of filariasis† caused by Wuchereria bancrofti or Brugia malayi.⁸ ¹³ ²⁰ ²¹ ²² ²³ Diethylcarbamazine (available in the US from the CDC) is the drug of choice.⁸ ¹³ Ivermectin (with or without albendazole) has been used.⁸ ¹³ ²⁰ ²¹ ²² ²³ A single dose of albendazole used in conjunction with either a single dose of diethylcarbamazine or ivermectin may be more effective than any one drug alone for suppression of microfilaremia caused by these organisms.⁸ ¹³ ²⁰ ²¹ ²²

Has been used to reduce microfilaremia in the treatment of loiasis† caused by Loa loa.⁸ Diethylcarbamazine (available in the US from the CDC) is the drug of choice;⁸ albendazole may be useful when diethylcarbamazine is ineffective or cannot be used, but repeated courses may be necessary.⁸

Hookworm Infections

Treatment of cutaneous larva migrans† (creeping eruption) caused by dog and cat hookworms.⁸ ¹³ Usually self-limited with spontaneous cure after several weeks or months; albendazole, ivermectin, or topical thiabendazole (not commercially available in the US) are drugs of choice when treatment is indicated.⁸ ¹³

Treatment of intestinal hookworm infections† caused by Ancylostoma duodenale or Necator americanus.⁸ ¹³ Albendazole, mebendazole, and pyrantel pamoate are drugs of choice.⁸ ¹³

Treatment of eosinophilic enterocolitis† caused by Ancylostoma caninum (dog hookworm).⁸ Treatment of choice is albendazole, mebendazole, pyrantel pamoate, or endoscopic removal of worms.⁸

Toxocariasis (Visceral Larva Migrans)

Treatment of toxocariasis† (visceral larva migrans) caused by Toxocara canis or T. cati (dog and cat roundworms).⁸ ¹³ Albendazole and mebendazole are drugs of choice.⁸ ¹³ Concomitant corticosteroids may be indicated in severe cases with cardiac, ocular, or CNS involvement.⁸ ¹³ Treatment may not be effective for ocular larva migrans; inflammation may be reduced by corticosteroid injections and surgery may be necessary for secondary damage.¹³

Strongyloidiasis

Treatment of strongyloidiasis† caused by Strongyloides stercoralis (threadworm).⁸ ¹³ Drug of choice is ivermectin; albendazole and thiabendazole are alternatives.⁸ ¹³

Trichinellosis

Treatment of trichinellosis† (trichinosis) caused by Trichinella spiralis.⁸ ¹³ Drug of choice is mebendazole; albendazole is an alternative.⁸ Concomitant corticosteroids usually recommended, especially for severe disease.⁸ ¹³ Corticosteroids alleviate symptoms of the inflammatory reaction and can be lifesaving when cardiac or CNS systems are involved.¹³

Trichostrongyliasis

Treatment of trichostrongyliasis† caused by Trichostrongylus.⁸ Pyrantel pamoate is drug of choice; albendazole and mebendazole are alternatives.⁸

Trichuriasis

Treatment of trichuriasis† caused by Trichuris trichiura (whipworm).⁸ ¹³ Mebendazole is drug of choice; albendazole and ivermectin are alternatives.⁸ ¹³

Capillariasis

Treatment of capillariasis† caused by Capillaria philippinensis.⁸ Mebendazole is drug of choice; albendazole is an alternative.⁸

Gnathostomiasis

Treatment of gnathostomiasis† caused by Gnathostoma spinigerum.⁸ Albendazole or ivermectin (with or without surgical removal) is recommended.⁸

Gongylonemiasis

Treatment of gongylonemiasis† caused by Gongylonema.⁸ Albendazole or surgical removal is recommended.⁸

Oesophagostomiasis

Treatment of oesophagostomiasis† caused by Oesophagostomum bifurcum.⁸ ¹⁹ Albendazole or pyrantel pamoate may be effective.⁸ ¹⁹

Trematode (Fluke) Infections

Treatment of infections caused by Clonorchis sinensis† (Chinese liver fluke).⁸ Albendazole and praziquantel are drugs of choice.⁸ Other anthelmintics (usually praziquantel) are recommended for all other fluke infections.⁸

Giardiasis

Treatment of giardiasis† caused by Giardia duodenalis (also known as G. lamblia or G. intestinalis).⁸ ¹³ Metronidazole, tinidazole, and nitazoxanide are drugs of choice.⁸ ¹³ Albendazole (alone or in conjunction with metronidazole) is an alternative;⁸ ¹³ may be particularly useful in children.¹³

Microsporidiosis

Treatment of intestinal microsporidiosis† caused by Encephalitozoon intestinalis.⁸ ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷ Albendazole is drug of choice,⁸ ¹³ but organism not eradicated in all patients and recurrence of diarrhea is common after therapy is stopped.¹³

Treatment of ocular microsporidiosis† caused by Encephalitozoon hellem, E. cuniculi, or Vittaforma corneae.⁸ ¹⁴ ¹⁵ ¹⁶ ¹⁷ Albendazole in conjunction with topical fumagillin (not commercially available in the US) has been recommended,⁸ but topical fumagillin generally not effective for lesions caused by V. corneae and keratoplasty may be necessary.⁸

Treatment of disseminated microsporidiosis† caused by E. hellem, E. cuniculi, E. intestinalis, Pleistophora, Trachipleistophora, or Brachiola vesicularum.⁸ ¹⁴ ¹⁵ ¹⁶ ¹⁷ Albendazole is drug of choice.⁸

Albendazole Dosage and Administration

Administration

Oral Administration

Administer orally with food.¹ Food, especially fatty food, increases bioavailability.¹ ³ ⁷

In patients (particularly young children) who have difficulty swallowing tablets whole, tablets may be crushed or chewed and swallowed with a drink of water.¹

Dosage

Pediatric Patients

Neurocysticercosis

Oral

Children weighing <60 kg: 15 mg/kg daily (up to 800 mg daily), administered as 2 equally divided doses with meals, for 8–30 days.¹ ⁸ Repeat as necessary.⁸

Children ≥6 years of age and weighing ≥60 kg: 400 mg twice daily with meals for 8–30 days.¹ ⁸ ⁵ Repeat as necessary.⁸

Hydatid Disease

Oral

Children <60 kg: 15 mg/kg daily (up to 800 mg daily), administered in 2 equally divided doses with meals for 28 days, followed by a 14-day albendazole-free interval.¹ Repeat for a total of 3 dosage cycles.¹

Children ≥6 years of age and weighing ≥60 kg: 400 mg twice daily with meals for 28 days, followed by a 14-day albendazole-free interval.¹ Repeat for a total of 3 dosage cycles.¹

Alternatively, 15 mg/kg daily (up to 800 mg daily) for 1–6 months has been recommended for treatment of hydatid cyst disease in pediatric patients.⁸

Ascariasis†

Oral

Single 400-mg dose.⁸

Baylisascariasis†

Oral

25–50 mg/kg daily for 10 days.¹⁸ Some clinicians recommend a 20-day regimen.⁸

Immediate treatment is recommended if infection is probable; treatment should not be delayed until patient is symptomatic.¹⁸

Enterobiasis†

Oral

400-mg initial dose followed by a second 400-mg dose given 2 weeks later.⁸

Consider treating household contacts, especially in situations in which multiple or repeated symptomatic infections occur.⁸ ¹³

Filariasis†

Filariasis Caused by Mansonella perstans†

Oral

400 mg twice daily for 10 days.⁸

Hookworm Infections†

Cutaneous Larva Migrans (Creeping Eruption)†

Oral

400 mg once daily for 3 days.⁸

Intestinal Hookworm Infections†

Oral

Single 400-mg dose.⁸

Perform a repeat stool examination (using a concentration technique) for eggs of Ancylostoma duodenale or Necator americanus 2 weeks after treatment; repeat dose if results are positive.¹³

Eosinophilic Enterocolitis Caused by Ancylostoma caninum†

Oral

Single 400-mg dose.⁸

Toxocariasis (Visceral Larva Migrans)†

Oral

400 mg twice daily for 5 days.⁸ Optimum duration of therapy not known; some clinicians recommend up to 20 days of treatment.⁸

Strongyloidiasis†

Oral

400 mg twice daily for 2 days.⁸

Repeated or prolonged therapy or use of other agents may be necessary in immunocompromised individuals or those with disseminated disease.⁸ ¹³

Trichinellosis†

Oral

400 mg twice daily for 8–14 days.⁸

Trichostrongyliasis†

Oral

Single 400-mg dose.⁸

Trichuriasis†

Oral

400 mg once daily for 3 days.⁸

Capillariasis†

Oral

400 mg once daily for 10 days.⁸

Gnathostomiasis†

Oral

400 mg twice daily for 21 days.^a

Gongylonemiasis†

Oral

10 mg/kg daily for 3 days.⁸

Trematode (Fluke) Infections†

Oral

10 mg/kg daily for 7 days.⁸

Giardiasis†

Oral

400 mg daily for 5 days (alone or in conjunction with metronidazole).⁸

Adults

Neurocysticercosis

Oral

Adults <60 kg: 15 mg/kg daily (up to 800 mg daily), administered in 2 equally divided doses with meals, for 8–30 days.¹ ⁸ Repeat as necessary.⁸

Adults ≥60 kg: 400 mg twice daily with meals for 8–30 days.¹ ⁸ ⁵ Repeat as necessary.⁸

Hydatid Disease

Oral

Adults <60 kg: 15 mg/kg daily (up to 800 mg daily), administered in 2 equally divided doses with meals for 28 days, followed by a 14-day albendazole-free interval.¹ Repeat for a total of 3 dosage cycles.¹

Adults ≥60 kg: 400 mg twice daily with meals for 28 days, followed by a 14-day albendazole-free interval.¹ Repeat for a total of 3 dosage cycles.¹

Alternatively, 400 mg twice daily for 1–6 months has been recommended for treatment of hydatid cyst disease in adults.⁸

Ascariasis†

Oral

Single 400-mg dose.⁸

Baylisascariasis†

Oral

25–50 mg/kg daily for 10 days.¹⁸ Some clinicians recommend a 20-day regimen.⁸

Enterobiasis†

Oral

400-mg initial dose followed by a second 400-mg dose given 2 weeks later.⁸

Consider treating household contacts, especially in situations in which multiple or repeated symptomatic infections occur.⁸ ¹³

Filariasis†

Filariasis Caused by Mansonella perstans†

Oral

400 mg twice daily for 10 days.⁸

Hookworm Infections†

Cutaneous Larva Migrans (Creeping Eruption)†

Oral

400 mg once daily for 3 days.⁸

Intestinal Hookworm Infections†

Oral

Single 400-mg dose.⁸

Perform a repeat stool examination (using a concentration technique) for eggs of Ancylostoma duodenale or Necator americanus 2 weeks after treatment; repeat dose if results are positive.¹³

Eosinophilic Enterocolitis Caused by Ancylostoma caninum†

Oral

Single 400-mg dose.⁸

Toxocariasis (Visceral Larva Migrans)†

Oral

400 mg twice daily for 5 days.⁸ Optimum duration of therapy not known; some clinicians recommend up to 20 days of treatment.⁸

Strongyloidiasis†

Oral

400 mg twice daily for 2 days.⁸

Repeated or prolonged therapy or use of other agents may be necessary in immunocompromised individuals or those with disseminated disease.⁸ ¹³

Trichinellosis†

Oral

400 mg twice daily for 8–14 days.⁸

Trichostrongyliasis†

Oral

Single 400-mg dose.⁸

Trichuriasis†

Oral

400 mg once daily for 3 days.⁸

Capillariasis†

Oral

400 mg once daily for 10 days.⁸

Gnathostomiasis†

Oral

400 mg twice daily for 21 days.^a

Gongylonemiasis†

Oral

10 mg/kg daily for 3 days.⁸

Trematode (Fluke) Infections†

Oral

10 mg/kg daily for 7 days.⁸

Giardiasis†

Oral

400 mg daily for 5 days (alone or in conjunction with metronidazole).⁸

Microsporidiosis†

Intestinal Microsporidiosis†

Oral

400 mg twice daily for 21 days.⁸

Ocular Microsporidiosis†

Oral

400 mg twice daily.⁸

Disseminated Microsporidiosis†

Oral

400 mg twice daily.⁸

Prescribing Limits

Pediatric Patients

Neurocysticercosis

Oral

Children weighing <60 kg: Maximum 800 mg daily.¹ ⁸

Hydatid Disease

Oral

Children weighing <60 kg: Maximum 800 mg daily.¹ ⁸

Adults

Neurocysticercosis

Oral

Adults weighing <60 kg: Maximum 800 mg daily.¹ ⁸

Hydatid Disease

Oral

Adults weighing <60 kg: Maximum 800 mg daily.¹ ⁸

Special Populations

No special population dosage recommendations at this time.

Cautions for Albendazole

Contraindications

Hypersensitivity to benzimidazole derivatives or any component in the formulation.¹

Warnings/Precautions

Warnings

Myelosuppression

Can cause bone marrow suppression, aplastic anemia, and agranulocytosis in patients with or without underlying hepatic dysfunction.¹ Reversible leukopenia has occurred in <1% of patients receiving the drug;¹ granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia reported rarely.¹ Rare fatalities reported due to granulocytopenia or pancytopenia.¹

Monitor blood counts at the beginning of each 28-day cycle of albendazole treatment and every 2 weeks during treatment.¹ Closer monitoring of blood counts is recommended in patients with liver disease, including hepatic echinococcosis, since these individuals may be more susceptible to bone marrow suppression leading to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia.¹

Discontinue albendazole if clinically important decreases in blood cell counts occur.¹

Fetal/Neonatal Morbidity and Mortality

Teratogenic effects (embryotoxicity, skeletal malformations) reported in rats and rabbits.¹

Exclude pregnancy before initiating albendazole.¹ Avoid pregnancy during and for at least 1 month after treatment.¹ If patient becomes pregnant, immediately discontinue the drug and apprise patient of the potential hazard to the fetus.¹ (See Pregnancy under Cautions.)

General Precautions

Precautions Related to Treatment of Neurocysticercosis

Adverse CNS effects (e.g., seizures and/or hydrocephalus) resulting from inflammatory reactions to damaged intracerebral cysts may occur when albendazole is used for treatment of neurocysticercosis.⁵ ⁷ Use appropriate corticosteroid and anticonvulsant treatment as required.¹ ⁵ ⁷ ⁸ Consider oral or IV corticosteroid therapy during the first week of treatment to prevent cerebral hypertension.¹

Destruction of cysticercal lesions by albendazole may cause retinal damage.¹ ⁵ ⁸ Prior to treatment of neurocysticercosis, examine patient for retinal lesions.¹ In those with such lesions, weigh the need for treatment against the possibility of irreparable retinal damage.¹ ⁵ ⁸

Hepatic Effects

Mild to moderate increases of hepatic enzymes occurred in about 16% of patients in clinical trials.¹ Hepatic enzymes generally return to normal when the drug is discontinued, but acute liver failure of uncertain casualty and hepatitis have been reported.¹

Perform liver function tests (hepatic transaminase concentrations) prior to each cycle of albendazole treatment and at least every 2 weeks during treatment.¹ If hepatic enzymes exceed twice the ULN, consider discontinuing the drug based on the individual patient circumstance.¹ Decisions to reinstitute albendazole when hepatic enzymes return to pretreatment levels should be individualized taking into account the risks and benefits of further albendazole treatment.¹ If the drug is reinstituted, perform laboratory tests frequently.¹

Specific Populations

Pregnancy

Category C.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Use during pregnancy only if benefits justify risks to the fetus and only when no alternative management is appropriate.¹

Use in women of childbearing age only after a negative pregnancy test; caution women against becoming pregnant while receiving albendazole and for at least 1 month after completing treatment.¹

Discontinue immediately if patient becomes pregnant.¹

Lactation

Distributed into animal milk; not known whether distributed into human milk.¹ Use with caution in nursing women.¹

Pediatric Use

Only limited experience in children <6 years of age.¹

Has been used for treatment of neurocysticercosis in pediatric patients as young as 1 year of age; efficacy appeared to be similar to that in adults and no unusual problems were reported.¹

Has been used without unusual problems for treatment of hydatid disease in infants and young children.¹

Geriatric Use

Experience in patients ≥65 years of age is limited.¹ Has been used without unusual problems for treatment of neurocysticercosis or hydatid disease in geriatric adults.¹

Hepatic Impairment

Individuals with hepatic impairment are at increased risk for hepatotoxicity and bone marrow suppression during albendazole treatment.¹

Discontinue albendazole if hepatic enzymes exceed twice the ULN or if clinically important decreases in blood cell counts occur.¹

Renal Impairment

Not studied, but clearance of albendazole unlikely to be affected.¹

Common Adverse Effects

Treatment of hydatid disease: Abnormal liver function test results, abdominal pain, nausea, vomiting, reversible alopecia, headache, dizziness.¹

Treatment of neurocysticercosis: Headache, nausea, vomiting, raised intracranial pressure, meningeal signs.¹

Interactions for Albendazole

Induces CYP1A isoenzyme.¹

Specific Drugs

Drug	Interaction	Comments
Cimetidine	Increased albendazole sulfoxide concentrations in bile and cystic fluid in hydatid cyst patients receiving cimetidine; plasma concentrations of albendazole sulfoxide unchanged¹
Dexamethasone	Increased albendazole trough concentrations¹
Praziquantel	Increased plasma concentrations and AUC of albendazole sulfoxide; time to peak concentrations and plasma elimination half-life of albendazole sulfoxide unchanged¹
Theophylline	Single albendazole dose does not affect theophylline metabolism; potential for interaction exists since albendazole induces CYP1A¹	Monitor theophylline concentrations during and after albendazole therapy¹

Albendazole Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract because of low aqueous solubility.¹

Rapidly converted to active metabolite (albendazole sulfoxide) before reaching systemic circulation.¹ Peak plasma concentrations of albendazole sulfoxide attained 2–5 hours after a dose.¹

Food

Oral bioavailability enhanced by coadministration with fatty meal (estimated fat content 40 g); plasma concentrations up to fivefold higher compared with administration in fasted state.¹

Distribution

Extent

Widely distributed throughout body.¹ Detected in urine, bile, liver, cyst wall, cyst fluid, and CSF.¹

Plasma Protein Binding

70% bound to plasma protein.¹

Elimination

Metabolism

Rapidly converted in liver to active metabolite (albendazole sulfoxide) which is responsible for anthelmintic activity.¹ Further metabolized to albendazole sulfone and other primary oxidative metabolites.¹

Elimination Route

Albendazole is undetectable in urine; <1% of albendazole sulfoxide detectable in urine.¹ Albendazole sulfoxide partially eliminated in bile.¹

Half-life

Albendazole sulfoxide: 8–12 hours.¹

Special Populations

Patients with extrahepatic obstruction: Increased albendazole sulfoxide serum concentration and prolonged half-life.¹ Elimination half-life may be 31.7 hours.¹

Patients with renal impairment: Pharmacokinetics not studied to date.¹

Geriatric patients: Pharmacokinetics not fully evaluated; data from patients up to 79 years of age with hydatid cysts suggest pharmacokinetics similar to young, healthy adults.¹

Stability

Storage

Oral

Tablets

20–25°C.¹

Actions and SpectrumActions

Broad-spectrum anthelmintic agent.¹

Benzimidazole derivative¹ ⁴ structurally related to thiabendazole and mebendazole.⁴

Principal anthelmintic effect of benzimidazoles appears to be specific, high-affinity binding to free β-tubulin in parasite cells,¹ ³ ⁴ resulting in selective inhibition of parasite microtubule polymerization,¹ ³ ⁴ and inhibition of microtubule-dependent uptake of glucose.² ³ ⁶

Benzimidazole derivatives bind to the β-tubulin of parasites at much lower concentrations than to mammalian β-tubulin protein;⁴ the drugs do not inhibit glucose uptake in mammals, and do not appear to have any effect on blood glucose concentrations in humans.² ⁶

Active against the larval forms of Echinococcus granulosus and Taenia solium.¹

Advice to Patients

Importance of taking with food to increase oral bioavailability.¹

Advise patients who experience difficulty swallowing the tablets whole (particularly young children) that the tablets may be crushed or chewed and swallowed with a drink of water.¹

Importance of completing full course of therapy, even if feeling better after a few days.¹

Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹

Importance of initiating albendazole therapy in women of childbearing age only after a negative pregnancy test is obtained.¹

Importance of cautioning women of childbearing age against becoming pregnant while receiving albendazole or within 1 month of completing treatment.¹

Importance of routine (every 2 weeks) monitoring of blood counts and liver function tests to detect harm to the bone marrow or liver.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Albendazole
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	200 mg	Albenza (with povidone)	GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Albenza 200MG Tablets (AMEDRA PHARMACEUTICALS): 12/$39.99 or 36/$109.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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20. Beach MJ, Streit TG, Addiss DG et al. Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren. Am J Trop Med Hyg. 1999; 60:479-86. [IDIS 427901] [PubMed 10466981]

21. Simonsen PE, Magesa SM, Dunyo SK et al. The effect of single dose ivermectin alone or in combination with albendazole on Wuchereria bancrofti infection in primary school children in Tanzania. Trans R Soc Trop Med Hyg. 2004; 98:462-72. [IDIS 517713] [PubMed 15186934]

22. Makunde WH, Kamugisha LM, Massaga JJ et al. Treatment of co-infection with bancroftian filariasis and onchocerciasis: a safety and efficacy study of albendazole with ivermectin compared to treatment of single infection with bancroftian filariasis. Filaria J. 2003; 2:15. [PubMed 14613509]

23. Bockarie MJ, Alexander NDE, Hyun P et al. Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes. Lancet. 1998; 351:162-8. [IDIS 398928] [PubMed 9449870]

a. AHFS drug information 2007. McEvoy GK, ed. Albendazole. Bethesda, MD: American Society of Health-System Pharmacists; 2007:45–7.

More Albendazole resources

Albendazole Side Effects (in more detail)
Albendazole Dosage
Albendazole Use in Pregnancy & Breastfeeding
Albendazole Drug Interactions
Albendazole Support Group
0 Reviews for Albendazole - Add your own review/rating

Albendazole Professional Patient Advice (Wolters Kluwer)

Albendazole MedFacts Consumer Leaflet (Wolters Kluwer)

albendazole Concise Consumer Information (Cerner Multum)

albendazole Advanced Consumer (Micromedex) - Includes Dosage Information

Albenza Prescribing Information (FDA)

Compare Albendazole with other medications

Ascariasis
Capillariasis
Cutaneous Larva Migrans
Cysticercus cellulosae
Echinococcus
Filariasis, Elephantiasis
Giardiasis
Gnathostomiasis
Hookworm Infection, Necator or Ancylostoma
Hydatid Disease
Liver Fluke

Tuesday, 2 October 2012

K-Tan

Generic Name: phenylephrine and pyrilamine (FEN il EFF rin and pir IL a meen)

Brand Names: Aldex D, Deconsal CT Tannate, K-Tan, Pyril Tann-12, Pyrlex PD, Ry-T-12, Ryna-12, Ryna-12S, Rynesa 12S, V-Tann, Viravan-S, Viravan-T

What is this drug?

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

Pyrilamine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

The combination of phenylephrine and pyrilamine is used to treat runny or stuffy nose, sneezing, watery eyes, and sinus congestion caused by allergies, the common cold, or the flu.

Phenylephrine and pyrilamine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about this drug?

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Do not use any other over-the-counter cough, cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine.

What should I discuss with my health care provider before taking this drug?

Do not use this medication if you are allergic to phenylephrine or pyrilamine, or to other antihistamines, decongestants, diet pills, stimulants, or ADHD medications. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Before taking phenylephrine and pyrilamine, tell your doctor if you are allergic to any drugs, or if you have:

heart disease or high blood pressure;

diabetes;

a thyroid disorder;

glaucoma;

kidney disease;

an enlarged prostate; or

problems with urination.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. This medication may pass into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take this drug?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label. Cold medicine is usually taken for only a short time until your symptoms clear up.

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

The chewable tablet must be chewed before you swallow it.

Shake the oral suspension (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

This medication can cause you to have unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

Store this medicine at room temperature, away from heat, light, and moisture.

What happens if I miss a dose?

Since cold or allergy medicine is usually taken only as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking this drug?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by pyrilamine. Tell your doctor if you regularly use any of these medicines, or any other cold or allergy medications.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Avoid drinking alcohol while you are taking this medication. Alcohol can add to drowsiness caused by an antihistamine. Do not use any other over-the-counter cough, cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant.

This drug side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

fast, pounding, or uneven heartbeat;

severe dizziness, anxiety, restless feeling, or nervousness, confusion, hallucinations, unusual thoughts or behavior;

easy bruising or bleeding, fever, chills, body aches, flu symptoms;

urinating less than usual or not at all; or

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

nausea, stomach pain, constipation, mild loss of appetite;

dry mouth;

warmth, tingling, or redness under your skin;

blurred vision;

dizziness, drowsiness;

problems with memory or concentration;

restless or excitability (especially in children);

sleep problems (insomnia); or

skin rash or itching.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect this drug?

Before taking phenylephrine and pyrilamine, tell your doctor if you are also taking:

a diuretic (water pill);

salicylates such as aspirin, Novasal, Doan's Extra Strength, Salflex, Tricosal, and others;

an antidepressant such as amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and others;

atropine (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

bronchodilators such as ipratroprium (Atrovent) or tiotropium (Spiriva);

bladder or urinary medications such as darifenacin (Enablex), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare); or

irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Anaspaz, Cystospaz, Levsin, and others), or propantheline (Pro-Banthine).

This list is not complete and there may be other drugs that can interact with phenylephrine and pyrilamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More K-Tan resources

K-Tan Side Effects (in more detail)
K-Tan Use in Pregnancy & Breastfeeding
K-Tan Drug Interactions
K-Tan Support Group
0 Reviews for K-Tan - Add your own review/rating

K-Tan MedFacts Consumer Leaflet (Wolters Kluwer)

Poly Hist Forte Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Ryna-12 Prescribing Information (FDA)

Rynesa 12S Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

Viravan-T Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Compare K-Tan with other medications

Allergies
Cold Symptoms
Hay Fever
Nasal Congestion
Sinusitis

Where can I get more information?

Your pharmacist can provide more information about phenylephrine and pyrilamine.

See also: K-Tan side effects (in more detail)

Saturday, 29 September 2012

Mucomyst

acetylcysteine

Dosage Form: solution

Mucomyst Description

Mucomyst brand of acetylcysteine is for inhalation (mucolytic agent) or oral administration (acetaminophen antidote), and available as sterile, unpreserved solutions (not for injection). The solutions contain 20% (Mucomyst-20) or 10% (Mucomyst-10) acetylcysteine, with edetate disodium in purified water. Sodium hydroxide is added to adjust pH to 7. Acetylcysteine is the N-acetyl derivative of the naturally-occurring amino acid, cysteine. The compound is a white crystalline powder with the molecular formula C5H9NO3S, a molecular weight of 163.2, and chemical name of N-acetyl-L-cysteine. Acetylcysteine has the following structural formula.

This product contains the following inactive ingredients: edetate disodium, sodium hydroxide, and purified water.

Mucomyst® (acetylcysteine solution, USP)

As a Mucolytic Agent

Mucomyst - Clinical Pharmacology

The viscosity of pulmonary mucous secretions depends on the concentrations of mucoprotein and, to a lesser extent, deoxyribonucleic acid (DNA). The latter increases with increasing purulence owing to the presence of cellular debris. The mucolytic action of acetylcysteine is related to the sulfhydryl group in the molecule. This group probably "opens" disulfide linkages in mucus thereby lowering the viscosity. The mucolytic activity of acetylcysteine is unaltered by the presence of DNA, and increases with increasing pH. Significant mucolysis occurs between pH 7 and 9.

Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcystine.

Occasionally, patients exposed to the inhalation of an acetylcysteine aerosol respond with the development of increased airways obstruction of varying and unpredictable severity. Those patients who are reactors cannot be identified a priori from a random patient population. Even when patients are known to have reacted previously to the inhalation of an acetylcysteine aerosol, they may not react during a subsequent treatment. The converse is also true; patients who have had inhalation treatments of acetylcysteine without incident may still react to a subsequent inhalation with increased airways obstruction. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the medication should be discontinued immediately.

Indications and Usage for Mucomyst

Mucomyst is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as:

: Chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung)

Acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis)

Pulmonary complications of cystic fibrosis

Tracheostomy care

Pulmonary complications associated with surgery

Use during anesthesia

Post-traumatic chest conditions

Atelectasis due to mucous obstruction

Diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial wedge catheterization)

Contraindications

Mucomyst is contraindicated in those patients who are sensitive to it.

Warnings

After proper administration of Mucomyst (acetylcysteine), an increased volume of liquified bronchial secretions may occur. When cough is inadequate, the airway must be maintained open by mechanical suction if necessary. Where there is a mechanical block due to foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with Mucomyst should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the medication should be discontinued immediately.

Precautions

General

With the administration of Mucomyst, the patient may observe initially a slight disagreeable odor that is soon not noticeable. With a face mask there may be stickiness on the face after nebulization. This is easily removed by washing with water.

Under certain conditions, a color change may occur in Mucomyst in the opened bottle. The light purple color is the result of a chemical reaction which does not significantly affect safety or mucolytic effectiveness of Mucomyst.

Continued nebulization of Mucomyst solution with a dry gas will result in an increased concentration of the drug in the nebulizer because of evaporation of the solvent. Extreme concentration may impede nebulization and efficient delivery of the drug. Dilution of the nebulizing solution with appropriate amounts of Sterile Water for Injection, USP, as concentration occurs, will obviate this problem.

Drug Interactions

Drug stability and safety of Mucomyst (acetylcysteine) when mixed with other drugs in a nebulizer have not been established.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Carcinogenesis

Carcinogenicity studies in laboratory animals have not been performed with acetylcysteine alone, nor with acetylcysteine in combination with isoproterenol.

Long-term oral studies of acetylcysteine alone in rats (12 months of treatment followed by 6 months of observation) at doses up to 1,000 mg/kg/day (5.2 times the human mucolytic dose) provided no evidence of oncogenic activity.

Mutagenesis

Published data1 indicate that acetylcysteine is not mutagenic in the Ames test, both with and without metabolic activation.

Impairment of Fertility

A reproductive toxicity test to assess potential impairment of fertility was performed with acetylcysteine (10%) combined with isoproterenol (0.05%) and administered as an aerosol into a chamber of 12.43 cubic meters. The combination was administered for 25, 30, or 35 minutes twice a day for 68 days before mating, to 200 male and 150 female rats; no adverse effects were noted in dams or pups. Females after mating were continued on treatment for the next 42 days.

Reproductive toxicity studies of acetylcysteine in the rat given oral doses of acetylcysteine up to 1,000 mg/kg (5.2 times the human mucolytic dose) have also been reported in the literature.1 The only adverse effect observed was a slight non-dose-related reduction in fertility at dose levels of 500 or 1,000 mg/kg/day (2.6 or 5.2 times the human mucolytic dose) in the Segment I study.

Pregnancy: Teratogenic Effects: Pregnancy Category B

In a teratology study of acetylcysteine in the rabbit, oral doses of 500 mg/kg/day (2.6 times the human mucolytic dose) were administered to pregnant does by intubation on days 6 through 16 of gestation. Acetylcysteine was found to be nonteratogenic under the conditions of the study.

In the rabbit, two groups (one of 14 and one of 16 pregnant females) were exposed to an aerosol of 10% acetylcysteine and 0.05% isoproterenol hydrochloride for 30 or 35 minutes twice a day from the 6th through the 18th day of pregnancy. No teratogenic effects were observed among the offspring.

Teratology and a perinatal and postnatal toxicity study in rats were performed with a combination of acetylcysteine and isoproterenol administered by the inhalation route. In the rat, two groups of 25 pregnant females each were exposed to the aerosol for 30 and 35 minutes, respectively, twice a day from the 6th through the 15th day of gestation. No teratogenic effects were observed among the offspring.

In the pregnant rat (30 rats per group), twice-daily exposure to an aerosol of acetylcysteine and isoproterenol for 30 or 35 minutes from the 15th day of gestation through the 21st day postpartum was without adverse effect on dams or newborns.

Reproduction studies of Mucomyst with isoproterenol have been performed in rats and of acetylcysteine alone in rabbits at doses up to 2.6 times the human dose. These have revealed no evidence of impaired fertility or harm to the fetus due to acetylcysteine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies may not always be predictive of human responses, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Mucomyst is administered to a nursing woman.

Adverse Reactions

Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Clinically overt acetylcysteine induced bronchospasm occurs infrequently and unpredictably even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.

Acquired sensitization to acetylcysteine has been reported rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to acetylcysteine.

Reports of irritation to the tracheal and bronchial tracts have been received and although hemoptysis has occurred in patients receiving acetylcysteine such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established.

Mucomyst Dosage and Administration

General

Mucomyst is available in rubber stoppered glass vials containing 4, 10, or 30 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride for Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. The 10% solution may be used undiluted.

Mucomyst does not contain an antimicrobial agent, and care must be taken to minimize contamination of the sterile solution. If only a portion of the solution in a vial is used, store the remainder in a refrigerator and use for inhalation only within 96 hours.

NEBULIZATION—FACE MASK, MOUTH PIECE, TRACHEOSTOMY

When nebulized into a face mask, mouth piece, or tracheostomy, 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution may be given every 2 to 6 hours; the recommended dose for most patients is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times a day.

NEBULIZATION TENT, CROUPETTE

In special circumstances it may be necessary to nebulize into a tent or Croupette, and this method of use must be individualized to take into account the available equipment and the patient's particular needs. This form of administration requires very large volumes of the solution, occasionally as much as 300 mL during a single treatment period.

If a tent or Croupette must be used, the recommended dose is the volume of Mucomyst (using 10% or 20%) that will maintain a very heavy mist in the tent or Croupette for the desired period. Administration for intermittent or continuous prolonged periods, including overnight, may be desirable.

DIRECT INSTILLATION

When used by direct instillation, 1 to 2 mL of a 10% to 20% solution may be given as often as every hour.

When used for the routine nursing care of patients with tracheostomy, 1 to 2 mL of a 10% to 20% solution may be given every 1 to 4 hours by instillation into the tracheostomy.

Mucomyst may be introduced directly into a particular segment of the bronchopulmonary tree by inserting (under local anesthesia and direct vision) a small plastic catheter into the trachea. Two to 5 mL of the 20% solution may then be instilled by means of a syringe connected to the catheter.

Mucomyst may also be given through a percutaneous intratracheal catheter. One to 2 mL of the 20% or 2 to 4 mL of the 10% solution every 1 to 4 hours may then be given by a syringe attached to the catheter.

DIAGNOSTIC BRONCHOGRAMS

For diagnostic bronchial studies, two to three administrations of 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution should be given by nebulization or by instillation intratracheally, prior to the procedure.

Administration of Aerosol

MATERIALS

Mucomyst may be administered using conventional nebulizers made of plastic or glass. Certain materials used in nebulization equipment react with acetylcysteine. The most reactive of these are certain metals (notably iron and copper) and rubber. Where materials may come into contact with Mucomyst solution, parts made of the following acceptable materials should be used: glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel. Silver may become tarnished after exposure, but this is not harmful to the drug action or to the patient.

NEBULIZING GASES

Compressed tank gas (air) or an air compressor should be used to provide pressure for nebulizing the solution. Oxygen may also be used but should be used with the usual precautions in patients with severe respiratory disease and CO2 retention.

APPARATUS

Mucomyst is usually administered as fine nebulae and the nebulizer used should be capable of providing optimal quantities of a suitable range of particle sizes.

Commercially available nebulizers will produce nebulae of Mucomyst satisfactory for retention in the respiratory tract. Most of the nebulizers tested will supply a high proportion of the drug solution as particles of less than 10 microns in diameter. Mitchell2 has shown that particles less than 10 microns should be retained in the respiratory tract satisfactorily.

Various intermittent positive pressure breathing devices nebulized Mucomyst with a satisfactory efficiency including: No. 40 De Vilbiss (The De Vilbiss Co., Somerset, Pennsylvania) and the Bennett Twin-Jet Nebulizer (Puritan Bennett Corp., Oak at 13th, Kansas City, Missouri).

The nebulized solution may be inhaled directly from the nebulizer. Nebulizers may also be attached to plastic face masks or plastic mouthpieces. Suitable nebulizers may also be fitted for use with the various intermittent positive pressure breathing (IPPB) machines. The nebulizing equipment should be cleaned immediately after use because the residues may clog the smaller orifices or corrode metal parts.

Hand bulbs are not recommended for routine use for nebulizing Mucomyst because their output is generally too small. Also, some hand-operated nebulizers deliver particles that are larger than optimum for inhalation therapy.

Mucomyst should not be placed directly into the chamber of a heated (hot pot) nebulizer. A heated nebulizer may be part of the nebulization assembly to provide a warm saturated atmosphere if the Mucomyst aerosol is introduced by means of a separate unheated nebulizer. Usual precautions for administration of warm saturated nebulae should be observed.

The nebulized solution may be breathed directly from the nebulizer. Nebulizers may also be attached to plastic face masks, plastic face tents, plastic mouth pieces, conventional plastic oxygen tents, or head tents. Suitable nebulizers may also be fitted for use with the various intermittent positive pressure breathing (IPPB) machines.

The nebulizing equipment should be cleaned immediately after use, otherwise the residues may occlude the fine orifices or corrode metal parts.

PROLONGED NEBULIZATION

When three fourths of the initial volume of Mucomyst solution have been nebulized, a quantity of Sterile Water for Injection (approximately equal to the volume of solution remaining) should be added to the nebulizer. This obviates any concentration of the agent in the residual solvent remaining after prolonged nebulization.

Compatibility

The physical and chemical compatibility of Mucomyst solutions with certain other drugs that might be concomitantly administered by nebulization, direct instillation, or topical application has been studied.

Mucomyst should not be mixed with certain antibiotics. For example, the antibiotics tetracycline hydrochloride, oxytetracycline hydrochloride, and erythromycin lactobionate were found to be incompatible when mixed in the same solution. These agents may be administered from separate solutions if administration of these agents is desirable.

The supplying of these data should not be interpreted as a recommendation for combining Mucomyst with other drugs. The table is not presented as positive assurance that no incompatibility will be present, since these data are based only on short-term compatibility studies done in the Mead Johnson Research Center. Manufacturers may change their formulations, and this could alter compatibilities. These data are intended to serve only as a guide for predicting compounding problems.

If it is deemed advisable to prepare an admixture, it should be administered as soon as possible after preparation. Do not store unused mixtures.

IN VITRO COMPATIBILITY1 TESTS OF ACETYLCYSTEINE
		RATIO TESTED6
PRODUCT AND/OR AGENT	COMPATIBILITY RATING	ACETYL- CYSTEINE	PRODUCT OR AGENT
1. The rating, Incompatible, is based on the formation of a precipitate, a change in clarity, immiscibility, or a rapid loss of potency of acetylcysteine or the active ingredient of the PRODUCT AND/OR AGENT in the admixture. The rating, Compatible, means that there was no significant physical change in the admixture when compared with a control solution of the PRODUCT AND/OR AGENT, and that there was no predicted chemical incompatibility. All of the admixtures have been tested for short-term chemical compatibility by assaying for the concentration of acetylcysteine after mixing.
2. The active ingredient in the PRODUCT AND/OR AGENT was also assayed after mixing. Some of the admixtures developed minor physical changes which were considered to be insufficient to rate the admixture Incompatible. These are listed in footnotes 3, 4, and 5.
3. A strong odor developed after storage for 24 hours at room temperature.
4. The admixture was a slightly darker shade of yellow than a control solution of the PRODUCT AND/OR AGENT.
5. A light tan color developed after storage for 24 hours at room temperature.
6. Entries are final concentrations. Values in parentheses relate volumes of Mucomyst solutions to volume of test solutions.
ANESTHETIC, GAS
Halothane	Compatible	20%	Infinite
Nitrous Oxide	Compatible	20%	Infinite
ANESTHETIC, LOCAL
Cocaine HCl	Compatible	10%	5%
Lidocaine HCl	Compatible	10%	2%
Tetracaine HCl	Compatible	10%	1%
ANTIBACTERIALS (A parenteral form of each antibiotic was used)
Bacitracin2,3 (mix and use at once)	Compatible	10%	5,000 U/mL
Chloramphenicol Sodium Succinate	Compatible	20%	20 mg/mL
Carbenicillin Disodium2 (mix and use at once)	Compatible	10%	125 mg/mL
Gentamicin Sulfate2	Compatible	10%	20 mg/mL
Kanamycin Sulfate2 (mix and use at once)	Compatible	10%	167 mg/mL
	Compatible	17%	85 mg/mL
Lincomycin HCl2	Compatible	10%	150 mg/mL
Neomycin Sulfate2	Compatible	10%	100 mg/mL
Novobiocin Sodium2	Compatible	10%	25 mg/mL
Penicillin G Potassium2	Compatible	10%	25,000 U/mL
(mix and use at once)	Compatible	10%	100,000 U/mL
Polymyxin B Sulfate2	Compatible	10%	50,000 U/mL
Cephalothin Sodium	Compatible	10%	110 mg/mL
Colistimethate Sodium2
(mix and use at once)	Compatible	10%	37.5 mg/mL
Vancomycin HCl2	Compatible	10%	25 mg/mL
Amphotericin B	Incompatible	4%-15%	1.0-4.0 mg/mL
Chlortetracycline HCl2	Incompatible	10%	12.5 mg/mL
Erythromycin Lactobionate	Incompatible	10%	15 mg/mL
Oxytetracycline HCl	Incompatible	10%	12.5 mg/mL
Ampicillin Sodium	Incompatible	10%	50 mg/mL
Tetracycline HCl	Incompatible	10%	12.5 mg/mL
BRONCHODILATORS
Isoproterenol HCl2	Compatible	3.0%	0.5%
Isoproterenol HCl2	Compatible	10%	0.05%
Isoproterenol HCl2	Compatible	20%	0.05%
Isoproterenol HCl	Compatible	13.3% (2 parts)	.33% (1 part)
Isoetharine HCl	Compatible	13.3%	.33% (1 part)
Epinephrine HCl	Compatible	13.3% (2 parts)	.33% (1 part)
CONTRAST MEDIA
Iodized Oil	Incompatible	20%/20 mL	40%/10 mL
DECONGESTANTS
Phenylephrine HCl2	Compatible	3.0%	.25%
Phenylephrine HCl	Compatible	13.3% (2 parts)	.17% (1 part)
ENZYMES
Chymotrypsin	Incompatible	5%	400 γ/mL
Trypsin	Incompatible	5%	400 γ/mL
SOLVENTS
Alcohol	Compatible	12%	10% - 20%
Propylene Glycol	Compatible	3%	10%
STEROIDS
Dexamethasone Sodium Phosphate	Compatible	16%	0.8 mg/mL
Prednisolone Sodium Phosphate5	Compatible	16.7%	3.3 mg/mL
OTHER AGENTS
Hydrogen Peroxide	Incompatible	(All ratios)
Sodium Bicarbonate	Compatible	20% (1 part)	4.2% (1 part)

Mucomyst® (acetylcysteine solution, USP) As An Antidote for Acetaminophen Overdose

Mucomyst - Clinical Pharmacology

(Antidotal) Acetaminophen is rapidly absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. The parent compound, which is nontoxic, is extensively metabolized in the liver to form principally the sulfate and glucuronide conjugates which are also nontoxic and are rapidly excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite which preferentially conjugates with hepatic glutathione to form the nontoxic cysteine and mercapturic acid derivatives which are then excreted by the kidney. Therapeutic doses of acetaminophen do not saturate the glucuronide and sulfate conjugation pathways and do not result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of a large overdose (150 mg/kg or greater) the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug being metabolized via the P-450 pathway. The increased formation of reactive metabolite may deplete the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis.

Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.

INDICATIONS

Acetylcysteine, administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen.

It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.

Contraindications

There are no contraindications to oral administration of acetylcysteine in the treatment of acetaminophen overdose.

Warnings

Generalized urticaria has been observed rarely in patients receiving oral acetylcysteine for acetaminophen overdose. If this occurs or other allergic symptoms appear, treatment with acetylcysteine should be discontinued unless it is deemed essential and the allergic symptoms can be otherwise controlled.

If encephalopathy due to hepatic failure becomes evident, acetylcysteine treatment should be discontinued to avoid further administration of nitrogenous substances. There are no data indicating that acetylcysteine influences hepatic failure, but this remains a theoretical possibility.

Precautions

Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with oral acetylcysteine may aggravate the vomiting. Patients at risk of gastric hemorrhage (e.g., esophageal varices, peptic ulcers, etc.) should be evaluated concerning the risk of upper gastrointestinal hemorrhage versus the risk of developing hepatic toxicity, and treatment with acetylcysteine given accordingly.

Dilution of the acetylcysteine (see Preparation of Mucomyst (Acetylcysteine) for Oral Administration) minimizes the propensity of oral acetylcysteine to aggravate vomiting.

Adverse Reactions

Oral administration of acetylcysteine, especially in the large doses needed to treat acetaminophen overdose, may result in nausea, vomiting and other gastrointestinal symptoms. Rash with or without mild fever has been observed rarely.

Mucomyst Dosage and Administration

General

Regardless of the quantity of acetaminophen reported to have been ingested, administer Mucomyst (acetylcysteine) immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen. Do not await results of assays for acetaminophen level before initiating treatment with Mucomyst. The following procedures are recommended:

The stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac. Syrup of ipecac should be given in a dose of 15 mL for children up to age 12 and 30 mL for adolescents and adults followed immediately by drinking copious quantities of water. The dose should be repeated if emesis does not occur in 20 minutes.

In the case of a mixed drug overdose, activated charcoal may be indicated. However, if activated charcoal has been administered, lavage before administering acetylcysteine treatment. Activated charcoal adsorbs acetylcysteine in vitro and may do so in patients and thereby may reduce its effectiveness.

Draw blood for predetoxification acetaminophen plasma assay and baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes.

Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. (Prepare Mucomyst for oral administration as described in the specific Dosage Guide and Preparation table.)

Determine subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy.
1. Predetoxification plasma acetaminophen level is clearly in the toxic range (See Acetaminophen Assays - Interpretation and Methodology below):
  
  Administer a first maintenance dose (70 mg/kg acetylcysteine) 4 hours after the loading dose. The maintenance dose is then repeated at 4-hour intervals for a total of 17 doses.
  
  Monitor hepatic and renal function and electrolytes throughout the detoxification process.
2. Predetoxification acetaminophen level could not be obtained:
  
  Proceed as in A.
3. Predetoxification acetaminophen level is clearly in the nontoxic range (beneath the dashed line on the nomogram) and you know that acetaminophen overdose occurred at least 4 hours before the predetoxification acetaminophen plasma assays:
  
  Discontinue administration of acetylcysteine.
4. Predetoxification acetaminophen level was in the non-toxic range, but time of ingestion was unknown or less than 4 hours.
  
  Because the level of acetaminophen at the time of the predetoxification assay may not be a peak value (peak may not be achieved before 4 hours post-ingestion), obtain a second plasma level in order to decide whether or not the full 17-dose detoxification treatment is necessary.

If the patient vomits any oral dose within 1 hour of administration, repeat that dose.

In the occasional instances where the patient is persistently unable to retain the orally administered acetylcysteine, the antidote may be administered by duodenal intubation.

Repeat SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes daily if the acetaminophen plasma level is in the potentially toxic range as discussed below.

Preparation of Mucomyst (Acetylcysteine) for Oral Administration

Oral administration requires dilution of the 20% solution with diet cola or other diet soft drinks, to a final concentration of 5% (see Dosage Guide and Preparation table). If administered via gastric tube or Miller-Abbott tube, water may be used as the diluent. The dilutions should be freshly prepared and utilized within one hour. Remaining undiluted solutions in opened vials can be stored in the refrigerator up to 96 hours. Mucomyst IS NOT APPROVED FOR PARENTERAL INJECTION.

Acetaminophen Assays - Interpretation and Methodology

The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of a drug ingested as an overdose is often inaccurate and is not a reliable guide to therapy of the overdose. THEREFORE, PLASMA OR SERUM ACETAMINOPHEN CONCENTRATIONS, DETERMINED AS EARLY AS POSSIBLE, BUT NO SOONER THAN 4 HOURS FOLLOWING AN ACUTE OVERDOSE, ARE ESSENTIAL IN ASSESSING THE POTENTIAL RISK OF HEPATOTOXICITY. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE OVERDOSE IS POTENTIALLY TOXIC.

INTERPRETATION OF ACETAMINOPHEN ASSAYS

When results of the plasma acetaminophen assay are available refer to the nomogram below to determine if plasma concentration is in the potentially toxic range. Values above the solid line connecting 200 µg/mL at 4 hours with 50 µg/mL at 12 hours are associated with a possibility of hepatic toxicity if an antidote is not administered. (Do not wait for assay results to begin acetylcysteine treatment.)

If the predetoxification plasma level is above the broken line continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus the broken line is placed 25% below the solid line which defines possible toxicity.

If the predetoxification plasma level is below the broken line described above, there is minimal risk of hepatic toxicity and acetylcysteine treatment can be discontinued.

ACETAMINOPHEN ASSAY METHODOLOGY

Assay procedures most suitable for determining acetaminophen concentrations utilize high pressure liquid chromatography (HPLC) or gas liquid chromatography (GLC). The assay should measure only parent acetaminophen and not conjugated. The assay procedures listed below fulfill this requirement:

SELECTED TECHNIQUES (NONINCLUSIVE)

HPLC:

1.: Blair D, Rumack BH. Clin Chem. 1977; 23(4): 743-745.
2.: Howie D, Andriaenssens Pl, Prescott LF. J Pharm Pharmacol 1977; 29(4): 235-237.

GLC

3.: Prescott LF. J Pharm Pharmacol 1971; 23(10): 807-808.

Colorimetric

4.: Glynn JP, Kendal SE. Lancet 1975; 1(May 17): 1147-1148.

Supportive Treatment of Acetaminophen Overdose

Maintain fluid and electrolyte balance based on clinical evaluation of state of hydration and serum electrolytes.

Treat as necessary for hypoglycemia.

Administer vitamin K1 if prothrombin time ratio exceeds 1.5 or fresh frozen plasma if the prothrombin time ratio exceeds 3.0.

Diuretics and forced diuresis should be avoided.

DOSAGE GUIDE AND PREPARATION

Doses in relation to body weight are:

Loading Dose of Mucomyst® (acetylcysteine)**
Body Weight		grams Acetylcysteine	mL of 20% Mucomyst	mL of Diluent	Total mL of 5% Solution
(kg)	(lb)
100-109	220-240	15	75	225	300
90-99	198-218	14	70	210	280
80-89	176-196	13	65	195	260
70-79	154-174	11	55	165	220
60-69	132-152	10	50	150	200
50-59	110-130	8	40	120	160
40-49	88-108	7	35	105	140
30-39	66-86	6	30	90	120
20-29	44-64	4	20	60	80

Maintenance Dose**
** If patient weighs less than 20 kg (usually patients younger than 6 years), calculate the dose of Mucomyst. Each mL of 20% Mucomyst contains 200 mg of acetylcysteine. The loading dose is 140 mg per kilogram of body weight. The maintenance dose is 70 mg/kg. Three (3) mL of diluent are added to each mL of 20% Mucomyst. Do not decrease the proportion of diluent.
Body Weight		grams Acetylcysteine	mL of 20% Mucomyst	mL of Diluent	Total mL of 5% Solution
(kg)	(lb)
100-109	220-240	7.5	37	113	150
90-99	198-218	7	35	105	140
80-89	176-196	6.5	33	97	130
70-79	154-174	5.5	28	82	110
60-69	132-152	5	25	75	100
50-59	110-130	4	20	60	80
40-49	88-108	3.5	18	52	70
30-39	66-86	3	15	45	60
20-29	44-64	2	10	30	40

Estimating Potential for Hepatoxicity

The following nomogram has been developed to estimate the probability that plasma levels in relation to intervals post ingestion will result in hepatoxocity.

Adapted from Rumack and Matthews, Pediatrics 1975; 55: 871-876.

How is Mucomyst Supplied

Mucomyst (acetylcysteine) is sterile, not for injection and can be used for inhalation (mucolytic agent) or oral administration (acetaminophen antidote). It is available as:

Mucomyst®-20: 20% acetylcysteine solution (200 mg acetylcysteine per mL).

NDC 0087-0570-03   Cartons of three 10 mL vials, 1 plastic dropper

NDC 0087-0570-09   Cartons of three 30 mL vials

NDC 0087-0570-07   Cartons of twelve 4 mL vials

Mucomyst®-10: 10% acetylcysteine solution (100 mg acetylcysteine per mL).

NDC 0087-0572-01   Cartons of three 10 mL vials, 1 plastic dropper

NDC 0087-0572-02   Cartons of three 30 mL vials

NDC 0087-0572-03   Cartons of twelve 4 mL vials

Storage

Store unopened vials at controlled room