Anthelmintics

Microbiology:
The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.
In the specified treatment indications albendazole appears to be active against the larval forms of the following organisms:

Echinococcus granulosus
Taenia solium

INDICATIONS AND USAGE:
ALBENZA is indicated for the treatment of the following infections:

Neurocysticercosis
ALBENZA is indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium.

Lesions considered responsive to albendazole therapy appear as nonenhancing cysts with no surrounding edema on contrast-enhanced computerized tomography. Clinical studies in patients with lesions of this type demonstrate a 74% to 88% reduction in number of cysts; 40% to 70% of albendazole-treated patients showed resolution of all active cysts.

Hydatid Disease
ALBENZA is indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus.

This indication is based on combined clinical studies which demonstrated non-infectious cyst contents in approximately 80 to 90% of patients given ALBENZA for 3 cycles of therapy of 28 days each (see DOSAGE AND ADMINISTRATION). Clinical cure (disappearance of cysts) was seen in approximately 30% of these patients, and improvement (reduction in cyst diameter of ≥25%) was seen in an additional 40%.

NOTE: When medically feasible, surgery is considered the treatment of choice for hydatid disease. When administering ALBENZA in the pre- or post-surgical setting, optimal killing of cyst contents is achieved when 3 courses of therapy have been given.

NOTE: The efficacy of albendazole in the therapy of alveolar hydatid disease caused by Echinococcus multilocularis has not been clearly demonstrated in clinical studies.

WARNINGS
Rare fatalities associated with the use of ALBENZA have been reported due to granulocytopenia or pancytopenia (see PRECAUTIONS). Albendazole has been shown to cause bone marrow suppression, aplastic anemia, and agranulocytosis in patients with and without underlying hepatic dysfunction. Blood counts should be monitored at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy with albendazole in all patients. Patients with liver disease, including hepatic echinococcosis, appear to be more at risk for bone marrow suppression leading to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia attributable to albendazole and warrant closer monitoring of blood counts. Albendazole should be discontinued in all patients if clinically significant decreases in blood cell counts occur.

Albendazole should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Patients should not become pregnant for at least 1 month following cessation of albendazole therapy. If a patient becomes pregnant while taking this drug, albendazole should be discontinued immediately. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

PRECAUTIONS
General
Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. Oral or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of anticysticeral therapy.

Pre-existing neurocysticercosis may also be uncovered in patients treated with albendazole for other conditions. Patients may experience neurological symptoms (e.g. seizures, increased intracranial pressure and focal signs) as a result of an inflammatory reaction caused by death of the parasite within the brain. Symptoms may occur soon after treatment; appropriate steroid and anticonvulsant therapy should be started immediately.

Cysticercosis may, in rare cases, involve the retina. Before initiating therapy for neurocysticercosis, the patient should be examined for the presence of retinal lesions. If such lesions are visualized, the need for anticysticeral therapy should be weighed against the possibility of retinal damage caused by albendazole-induced changes to the retinal lesion.

DOSAGE AND ADMINISTRATION:
Dosing of ALBENZA will vary, depending upon which of the following parasitic infections is being treated. In young children, the tablets should be crushed or chewed and swallowed with a drink of water.

Indication	Patient Weight	Dose	Duration
Hydatid Disease	60 kg or greater	400 mg twice daily, with meals	28-day cycle followed by a 14-day albendazole-free interval, for a total of 3 cycles
	less than 60 kg	15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)
	NOTE: When administering ALBENZA in the pre- or post-surgical setting, optimal killing of cyst contents is achieved when 3 courses of therapy have been given.
Neurocysticercosis	60 kg or greater	400 mg twice daily, with meals	8 to 30 days
	less than 60 kg	15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)

Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. Oral or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of treatment.

Additional dosing (ADULT):
Source:  Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; April 30, 2014.
See reference for additional guidance.

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Neurocysticercosis:
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<60 kg: 15 mg/kg/day in 2 divided doses (maximum: 800 mg/day) for 8-30 days
≥60 kg: 800 mg/day in 2 divided doses for 8-30 days

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Ancylostoma caninum, Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm) (unlabeled use)
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Oral: 400 mg as a single dose

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Cutaneous larva migrans (unlabeled use):
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Oral: 400 mg once daily for 3 days

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Enterobius vermicularis (pinworm) (unlabeled use):
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Oral: 400 mg as a single dose; repeat in 2 weeks

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Giardia duodenalis (giardiasis) (unlabeled use):
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Oral: 400 mg once daily for 5 days

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Gnathostoma spinigerum (unlabeled use):
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Oral: 800 mg/day in 2 divided doses for 21 days

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Disseminated microsporidiosis (unlabeled use):
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Oral: 800 mg/day in 2 divided doses

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Echinococcus granulosus (tapeworm) (unlabeled use):
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Oral: 800 mg/day in 2 divided doses for 1-6 months

SUPPLIED:
ALBENZA is supplied as 200 mg, white to off-white, circular, biconvex, bevel-edged, film coated TILTAB tablet embossed "ap" and "550". They are supplied as follows:

Bottles of 2 NDC 52054-550-22
Bottles of 28 NDC 52054-550-28

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

ALBENZA and TILTAB are registered trademarks of GlaxoSmithKline, used with permission.

SOURCE: Package insert data:

Microbiology:
Ivermectin is a member of the avermectin class of broad-spectrum antiparasitic agents which have a unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).

The selective activity of compounds of this class is attributable to the facts that some mammals do not have glutamate-gated chloride channels and that the avermectins have a low affinity for mammalian ligand-gated chloride channels. In addition, ivermectin does not readily cross the blood-brain barrier in humans.

Ivermectin is active against various life-cycle stages of many but not all nematodes. It is active against the tissue microfilariae of Onchocerca volvulus but not against the adult form. Its activity against Strongyloides stercoralis is limited to the intestinal stages.

INDICATIONS AND USAGE:
STROMECTOL is indicated for the treatment of the following infections:

Strongyloidiasis of the intestinal tract. STROMECTOL is indicated for the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis.

This indication is based on clinical studies of both comparative and open-label designs, in which 64-100% of infected patients were cured following a single 200-mcg/kg dose of ivermectin.

Onchocerciasis. STROMECTOL is indicated for the treatment of onchocerciasis due to the nematode parasite Onchocerca volvulus.

This indication is based on randomized, double-blind, placebo-controlled and comparative studies conducted in 1427 patients in onchocerciasis-endemic areas of West Africa. The comparative studies used diethylcarbamazine citrate (DEC-C).

NOTE: STROMECTOL has no activity against adult Onchocerca volvulus parasites. The adult parasites reside in subcutaneous nodules which are infrequently palpable. Surgical excision of these nodules (nodulectomy) may be considered in the management of patients with onchocerciasis, since this procedure will eliminate the microfilariae-producing adult parasites.

CONTRAINDICATIONS
STROMECTOL is contraindicated in patients who are hypersensitive to any component of this product.

WARNINGS
Historical data have shown that microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions in patients with onchocerciasis. These reactions are probably due to allergic and inflammatory responses to the death of microfilariae. Patients treated with STROMECTOL for onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, probably, or definitely related to the drug itself.

The treatment of severe Mazzotti reactions has not been subjected to controlled clinical trials. Oral hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to treat postural hypotension. Antihistamines and/or aspirin have been used for most mild to moderate cases.

DOSAGE AND ADMINISTRATION:
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Strongyloidiasis
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The recommended dosage of STROMECTOL for the treatment of strongyloidiasis is a single oral dose designed to provide approximately 200 mcg of ivermectin per kg of body weight. See Table 1 for dosage guidelines. Patients should take tablets on an empty stomach with water. In general, additional doses are not necessary. However, follow-up stool examinations should be performed to verify eradication of infection.

Table 1: Dosage Guidelines for STROMECTOL for Strongyloidiasis:

Body Weight (kg)	Single Oral Dose
	Number of 3-mg Tablets
15-24	1 tablet
25-35	2 tablets
36-50	3 tablets
51-65	4 tablets
66-79	5 tablets
≥80	200 mcg/kg

----------------------------------------
Onchocerciasis
----------------------------------------
The recommended dosage of STROMECTOL for the treatment of onchocerciasis is a single oral dose designed to provide approximately 150 mcg of ivermectin per kg of body weight. See Table 2 for dosage guidelines. Patients should take tablets on an empty stomach with water.  In mass distribution campaigns in international treatment programs, the most commonly used dose interval is 12 months. For the treatment of individual patients, retreatment may be considered at intervals as short as 3 months.

Table 2: Dosage Guidelines for STROMECTOL for Onchocerciasis:

Body Weight (kg)	Single Oral Dose
	Number of 3-mg Tablets
15-25	1 tablet
26-44	2 tablets
45-64	3 tablets
65-84	4 tablets
=85	150 mcg/kg

Additional dosing (ADULT):
Source:  Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; April 30, 2014.
See reference for additional guidance.

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Ascariasis due to Ascaris lumbricoides (unlabeled use):
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Oral: 200 mcg/kg as a single dose

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Filariasis due to Mansonella ozzardi (unlabeled use):
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Oral: 6 mg as a single dose

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Lice due to Pediculus humanus capitis, Pediculus humanus corporis, Phthirus pubis (unlabeled use):
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Oral: 200 mcg/kg/dose; generally requires >1 dose; number of doses and dosage intervals have not been established

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Pediculus humanus capitis:
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Oral: 400 mcg/kg/dose every 7 days for 2 doses

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Scabies due to Sarcoptes scabieiin immunocompromised patients (unlabeled use):
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Oral: 200 mcg/kg as a single dose; may repeat dose in 14 days

SUPPLIED:
No. 8495 -- Tablets STROMECTOL 3 mg are white, round, flat, bevel-edged tablets coded MSD on one side and 32 on the other side. They are supplied as follows:

NDC 0006-0032-20 unit dose packages of 20.

Storage

Store at temperatures below 30°C (86°F).
SOURCE: Package insert data

Microbiology:
Mode of Action
Mebendazole inhibits the formation of the worms’ microtubules and causes the worms’ glucose depletion.

INDICATIONS AND USAGE:
Mebendazole tablets are indicated for the treatment of Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (common roundworm), Ancylostoma duodenale (common hookworm), Necator americanus (American hookworm) in single or mixed infections.

Efficacy varies as a function of such factors as preexisting diarrhea and gastrointestinal transit time, degree of infection, and helminth strains. Efficacy rates derived from various studies are shown in the table below:

	Pinworm (enterobiasis)	Whipworm (trichuriasis)	Common Roundworm (ascariasis)	Hookworm
Cure rates mean	95%	68%	98%	96%
Egg reduction mean	--	93%	99%	99%

CONTRAINDICATIONS
Mebendazole is contraindicated in persons who have shown hypersensitivity to the drug.

WARNINGS
There is no evidence that mebendazole, even at high doses, is effective for hydatid disease. There have been rare reports of neutropenia and agranulocytosis when mebendazole was taken for prolonged periods and at dosages substantially above those recommended.

DOSAGE AND ADMINISTRATION:
The same dosage schedule applies to children and adults. The tablet may be chewed, swallowed, or crushed and mixed with food.

	Pinworm (enterobiasis)	Whipworm (trichuriasis)	Common Roundworm (ascariasis)	Hookworm
Dose	1 tablet, once	1 tablet morning and evening for 3 consecutive days	1 tablet morning and evening for 3 consecutive days	1 tablet morning and evening for 3 consecutive days

If the patient is not cured three weeks after treatment, a second course of treatment is advised. No special procedures, such as fasting or purging, are required.

Additional dosing (ADULT):
Source:  Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; April 30, 2014.
See reference for additional guidance.

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Ancylostoma duodenale (hookworm), Necator americanus (hookworm), Ascaris lumbricoides (roundworm), Strongyloides stercoralis (roundworm), Taenia solium (tapeworms), Trichuris trichiura (whipworm), mixed infection:
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Oral: 100 mg twice daily for 3 days; repeat in 3 weeks if not cured with initial treatment

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Enterobius vermicularis (pinworm):
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Oral: 100 mg as a single dose; repeat in 2 and 4 weeks

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Ancylostoma duodenale (hookworm), Ascaris lumbricoides (roundworm), Necator americanus (hookworm), Trichuris trichiura (whipworm):
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500 mg as a single dose

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Giardia duodenalis (giardiasis):
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Oral: 200 mg 3 times daily for 5 days

SUPPLIED:
Mebendazole 100 mg, chewable, round, light peach-colored, unscored tablets, debossed “93” and “107” on one side and plain on the other side, supplied in boxes of twelve tablets, blister packaged.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

SOURCE: Package insert data:

INDICATIONS AND USAGE:
BILTRICIDE is indicated for the treatment of infections due to: all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated).

CONTRAINDICATIONS
BILTRICIDE is contraindicated in patients who previously have shown hypersensitivity to the drug or any of the excipients. Since parasite destruction within the eye may cause irreversible lesions, ocular cysticercosis must not be treated with this compound.

Concomitant administration with strong Cytochrome P450 (P450) inducers, such as rifampin, is contraindicated since therapeutically effective blood levels of praziquantel may not be achieved (see PRECAUTIONS/Drug Interactions). In patients receiving rifampin who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment (see PRECAUTIONS/Drug Interactions).

WARNINGS
Therapeutically effective levels of BILTRICIDE may not be achieved when administered concomitantly with strong P450 inducers, such as rifampin.

DOSAGE AND ADMINISTRATION:
The dosage recommended for the treatment of schistosomiasis is:
20 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours.

The recommended dose for clonorchiasis and opisthorchiasis is: 25 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours.

The tablets should be washed down unchewed with water during meals. Keeping the tablets or segments thereof in the mouth can reveal a bitter taste which can promote gagging or vomiting.

Additional dosing (ADULT):
Source:  Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; April 30, 2014.
See reference for additional guidance.

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Tapeworms (unlabeled use):
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Oral: 5-10 mg/kg as a single dose (25 mg/kg for Hymenolepis nana)

SUPPLIED:
BILTRICIDE is supplied as a 600 mg white to orange tinged, film-coated, oblong tablet with three scores. The tablet is coded with “BAYER” on one side and “LG” on the reverse side. When broken, each of the four segments contains 150 mg of active ingredient so that the dosage can be easily adjusted to the patient’s bodyweight.

Segments are broken off by pressing the score (notch) with thumbnails. If 1/4 of a tablet is required, this is best achieved by breaking the segment from the outer end.

BILTRICIDE is available in bottles of 6 tablets.

SOURCE: Package insert data:

CLINICAL PHARMACOLOGY
Pin-X® has demonstrated anthelmintic activity against Enterobius vermicularis (pinworm) and Ascaris lumbricoides (common roundworm). The anthelmintic action is probably due to the neuromuscular blocking property of the drug. Pin-X® is partially absorbed after an oral dose. Plasma levels of unchanged drug are low. Peak levels (0.05 - 0.13 micrograms per milliliter) are reached in 1-3 hours. Quantities greater than 50% of administered drug are excreted in feces as the unchanged form, whereas only 7% or less of the dose is found in urine as the unchanged form of the drug and its metabolites.

Symptoms suggestive of pinworm infestation:
Pruritis Ani (itching in the anal area), insomnia, gastrointestinal distress, irritability, enuresis (bed wetting) and secondary infection due to localized scratching are symptoms of pinworms. However, you should make a visual inspection and confirmation of the pinworms before using this product.

How to find and identify the pinworm:
A pinworm is a small round worm that lives in the body of other animals. They are 1/4 to 1/2 inch long and have white bodies and pointed tails. There are several kinds of pinworms, however, only one kind, Enterobius vermicularis, commonly infects human beings. The worms can usually be detected during the hours of sleep when the worm migrates out of the anus onto the surrounding skin.

The life cycle of the pinworm:
The young worms live in the upper part of the large intestine. When they are ready to lay eggs, they crawl down the rectum and out the intestinal opening called the anus, usually at night. They lay eggs on the surrounding skin. This movement causes swelling and severe itching.

How pinworms are spread and how to avoid spreading:
The eggs fall off into the bedding or clothing and may be picked up under the fingernails in scratching. If the eggs are swallowed, they reach the intestine and become adult pinworms. Therefore, to avoid the spreading of pinworms all areas should be as clean as possible.

INDICATIONS AND USAGE:
For the treatment of pinworms.

CONTRAINDICATIONS
Hypersensitivity to any of the ingredients.

WARNINGS
KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Abdominal cramps, nausea, vomiting, diarrhea, headache, or dizziness sometimes occur after taking this drug. If any of these conditions persist, consult a doctor. If you are pregnant or have liver disease, do not take this product unless directed by a doctor.

DOSAGE AND ADMINISTRATION:
Information for Patients
Phenylketonurics
Pin-X® Chewable Tablets contain phenylalanine 11.8 mg per tablet.

DIRECTIONS FOR USE
Read package insert carefully before taking this medication. Take only according to directions and do not exceed the recommended dosage unless directed by a doctor. Medication should only be taken one time as a single dose; do not repeat treatment unless directed by a doctor. When one individual in a household has pinworms, the entire household should be treated unless otherwise advised. See WARNINGS. If any worms other than pinworms are present before or after treatment, consult a doctor. If any symptoms or pinworms are still present after treatment, consult a doctor. This product can be taken any time of day, with or without meals. It may be taken alone or with milk or fruit juice. Use of a laxative is not necessary prior to, during, or after medication.

Adults and children 2 years to under 12 years of age: oral dosage is a single dose of 5 milligrams of pyrantel base per pound, or 11 milligrams per kilogram, of body weight not to exceed 1 gram. Dosage information is summarized on the following schedule:

Weight	Dosage (taken as a single dose)
Less than 25 pounds (11 kg) or under 2 years old	Do not use unless directed by a doctor
25 to 37 pounds (11 to 16 kg)	1/2 tablet
38 to 62 pounds (17 to 28 kg)	1 tablet
63 to 87 pounds (29 to 39 kg)	1 1/2 tablets
88 to 112 pounds ( 40 to 50 kg)	2 tablets
113 to 137 pounds (51 to 62 kg)	2 1/2 tablets
138 to 162 pounds (63 to 73 kg)	3 tablets
163 to 187 pounds (74 to 84 kg)	3 1/2 tablets
over 187 pounds (over 84 kg)	4 tablets

Additional dosing (ADULT):
Source:  Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.; April 30, 2014.
See reference for additional guidance.

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Ancylostoma duodenale (hookworm), Ascariasis lumbricoides (roundworm), Necator americanus (hookworm) (unlabeled use):
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11 mg/kg (maximum: 1 g/dose) administered once daily for 3 days

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Moniliformis (unlabeled use):
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11 mg/kg administered as a single dose; repeat twice 2 weeks apart

SUPPLIED:
Pin-X® Chewable Tablets are supplied as round, flat faced, orange color, orange flavored chewable tablets with “Pin-X” debossed over a score line on one side and plain on the reverse side, in bottles of 12.

Store at 15°-30°C (59°-86°F).

SOURCE: Package insert data: