Class: Anthelmintics
VA Class: AP200
Chemical Name: A mixture of Ivermectin Component B1a ((2aE,4E,8E) - (5′S,6S,6′R,7S,11R,13R,15S,17aR,20R,20aR,20bS) - 6′ - (S) - sec - butyl - 3′,4′,5′,6,6′,7,10,11,14,15,17a,20,20a,20b - tetradecahydro - 20,20b - dihydroxy - 5′,6,8,19 - tetramethyl - 17 - oxospiro[11,15 - methano - 2H,13H,17H - furo[4,3,2 - pq][2,6] - benzodioxacyclooctadecin - 13,2′ - [2H]pyran] - 7 - yl - 2,6 - dideoxy - 4 - O - (2,6 - dideoxy - 3 - O - methyl - α - l - arabino - hexopyranosyl) - 3 - O - methyl - α - l - arabino - hexopyranoside) and Ivermectin Component B1b ((2aE,4E,8E) - (5′S,6S,6′R,7S,11R,13R,15S,17aR,20R,20aR,20bS) - 3′,4′,5′,6,6′,7,10,11,14,15,17a,20,20a,20b - tetradecahydro - 20,20b - dihydroxy - 6′ - isopropyl - 5′,6,8,19 - tetramethyl - 17 - oxospiro[11,15 - methano - 2H,13H,17H - furo[4,3,2 - pq][2,6] - benzodioxacyclooctadecin - 13,2′ - [2H]pyran] - 7 - yl - 2,6 - dideoxy - 4 - O - (2,6 - dideoxy - 3 - O - methyl - α - l - arabino - hexopyranosyl) - 3 - O - methyl - α - l - arabino - hexopyranoside)
Molecular Formula: A mixture of Ivermectin Component B_1a (C₄₈H₇₄O₁₄) and Ivermectin Component B_1b (C₄₇H₇₂O₁₄)
CAS Number: 70288-86-7
Brands: Stromectol

Introduction

Anthelmintic and anti-ectoparasitic agent; avermectin derivative.^{1 4 6 14 15 18 19 33 45}

Uses for Ivermectin

Ascariasis

Treatment of ascariasis† caused by Ascaris lumbricoides.^{3 96} Albendazole and mebendazole are drugs of choice.^{3 80} Ivermectin also recommended as a drug of choice,³ but efficacy not clearly established.⁸⁰

Filariasis

Treatment of onchocerciasis (filariasis caused by Onchocerca volvulus; commonly referred to as river blindness).^{1 2 3 6 8 17 20 21 22 42 110} Drug of choice.^{1 2 3 6 8 17 20 21 22 42} Used in individual patients and in mass treatment and control programs.^{4 5 6 7 11 16 17 19 110} Does not kill adult O. volvulus worms, but decreases microfilarial load in skin for approximately 6–12 months following a single dose.^{1 2 8 11 18 20 80}

Treatment of filariasis caused by Mansonella streptocerca†.^{3 21} Diethylcarbamazine (available in the US from CDC) and ivermectin are drugs of choice.^{3 21} Diethylcarbamazine is potentially curative since it is active against both adult worms and microfilariae; ivermectin is effective only against microfilariae.^{3 21 22}

Has been used for treatment of filariasis caused by M. ozzardi†.^{3 23}

Treatment of filariasis caused by Wuchereria bancrofti† or Brugia malayi†; used alone or in conjunction with albendazole or diethylcarbamazine.^{2 3 4 19 63 64 65 76 77 80 90} Ivermectin does not kill adult worms, but may play an important role in mass treatment programs to suppress microfilaremia and thereby interrupt transmission in endemic areas.^{80 90} Diethylcarbamazine is usual drug of choice,^{2 3} especially for individual patients when the goal is to kill the adult worm.^{80 81 82 83 90}

Slideshow: Grapefruit and Medicines: A Possible Deadly Mix?

Has been used in conjunction with albendazole to treat co-infection with W. bancrofti† and O. volvulus.⁷⁶

Has been used to reduce microfilaremia in the treatment of loiasis caused by Loa loa†.^{3 8 35 67} Generally not recommended since rapid killing of microfilariae increases risk of encephalopathy.³ (See Encephalopathy Risk in Onchocerciasis and Loiasis under Cautions.) Drug of choice for loiasis is diethylcarbamazine;^{3 80} preferred alternative is albendazole since it has a slower onset of action and decreased risk of encephalopathy compared with ivermectin.³

Gnathostomiasis

Treatment of gnathostomiasis† caused by Gnathostoma spinigerum.³ Drug of choice (with or without surgical removal) is albendazole or ivermectin.³

Hookworm Infections

Treatment of cutaneous larva migrans† (creeping eruption) caused by Ancylostoma braziliense (dog and cat hookworm) or Ancylostoma caninum (dog hookworm).^{2 3 15 50 69} Usually self-limited with spontaneous cure after several weeks or months;^{3 15 50 69} when treatment is indicated, drug of choice is albendazole or ivermectin^{15 50 69} and alternative is topical thiabendazole (topical preparations not commercially available in the US).³

Do not use for treatment of intestinal hookworm infections caused by Ancylostoma duodenale or Necator americanus.^{13 35 70 71 80} Appears to have little or no activity against these hookworms.^{13 35 70 71 80} Albendazole, mebendazole, and pyrantel pamoate are drugs of choice.³

Strongyloidiasis

Treatment of intestinal (i.e., nondisseminated) strongyloidiasis caused by Strongyloides stercoralis.^{1 2 3} Drug of choice;³ alternatives are albendazole and thiabendazole.³

Has been used for treatment of strongyloidiasis hyperinfection syndrome† and for treatment of strongyloidiasis in immunocompromised patients.^{2 3 98} Repeated, prolonged, or use of other drugs may be necessary in these situations;^{2 3 98} treatment failures reported.¹⁰²

Empiric treatment of strongyloidiasis before transplantation to prevent hyperinfection in hematopoietic stem cell transplant (HSCT) recipients†.⁹ Such treatment recommended by CDC, IDSA, and ASBMT in HSCT candidates with positive strongyloidiasis screening tests and those with possible exposure (e.g., unexplained eosinophilia and travel or residence history suggestive of S. stercoralis exposure [even if seronegative or stool-negative]).⁹ Data insufficient to recommend prophylaxis after HSCT to prevent recurrence of strongyloidiasis in such patients.⁹

Trichuriasis

Treatment of trichuriasis† caused by Trichuris trichiura (whipworm).^{3 96} Mebendazole is drug of choice; alternatives are albendazole and ivermectin.³

Pediculosis

Treatment of pediculosis capitis† (head lice infestation).^{3 4 14 57 62} AAP and others usually recommend topical permethrin 1% as drug of choice and topical malathion 0.5% when permethrin resistance is suspected.^{3 57 62} Ivermectin also may be a drug of choice because of ease of use and efficacy⁸⁰ or may be reserved for when there is no response to topical agents.^{13 80}

Alternative for treatment of pediculosis pubis† (pubic lice infestation).^{3 10} Drug of choice is topical permethrin 1% or topical pyrethrins with piperonyl butoxide.^{2 10}

Alternative for treatment of pediculosis corporis† (body lice infestation).¹⁰⁷ In some cases, body louse infestations may be treated by improved hygiene and by decontaminating clothes and bedding by washing at temperatures that kill lice.^{2 107} If the infestation is severe, a pediculicide also should be used (e.g., topical permethrin, topical pyrethrins with piperonyl butoxide, topical malathion, oral ivermectin).^{106 107}

Scabies

Treatment of scabies† (mite infestation).^{3 4 10 32 46 47 52 53 57 68 108 109} CDC, AAP, and others usually recommend topical permethrin 5% as scabicide of choice;^{2 10 53 57 105} CDC also recommends ivermectin as a drug of choice.¹⁰

Ivermectin may be particularly useful in refractory scabies infestations, for control of outbreaks in institutions, and when compliance with topical therapy is difficult.^{10 32 46 47 52 53 57 68 108 109}

Has been used for treatment of severe or crusted (Norwegian) scabies†.^{2 3 10 108 109} May be a drug of choice in immunocompromised patients^{3 10 52 57 100 108 109} or may be reserved for refractory infections or when topical therapy is not tolerated.^{2 3} Aggressive treatment (multiple-dose ivermectin regimen or concomitant use with a topical scabicide) may be necessary.^{10 108 109}

Ivermectin Dosage and Administration

General

Onchocerciasis

• Does not kill adult O. volvulus worms, but may decrease microfilarial load in skin for approximately 6–12 months following a single dose.^{1 2 8 11 18 20 80 110} Follow-up and retreatment required since adult female worms continue to produce microfilaria for 9–15 years.^{5 7 19}

• Recommendations for retreatment intervals vary.^{1 80} For individual patients, retreatment once every 6–12 months until asymptomatic has been recommended;^{2 3} intervals as short as 3 months can be considered.¹ When used in mass treatment and control programs, retreatment often given at 12-month intervals; in some programs, patients may be routinely retreated before 12 months if symptoms of pruritus develop.^{80 110} Some programs use 6-month intervals to suppress microfilarial counts to a level where transmission can be interrupted.⁸⁰

• Adjunctive surgical excision of subcutaneous nodules may help eliminate microfilariae-producing adult worms,^{1 7 8} but there is no evidence that nodulectomies reduce blindness associated with onchocerciasis.⁸⁰

Strongyloidiasis

• After treatment, perform follow-up stool examinations to verify eradication of S. stercoralis;¹ retreatment indicated if recrudescence of larvae observed.¹

• Optimal dosage for treatment of intestinal strongyloidiasis in immunocompromised (e.g., HIV-infected) patients not established.¹ Several courses of therapy (i.e., at intervals of 2 weeks) may be necessary; cure may not be achieved.¹ Control of extra-intestinal strongyloidiasis in such patients is difficult; once-monthly suppressive treatment may be helpful.¹

Scabies†

• Consider treating family members of patients with scabies since asymptomatic scabies is common.⁸⁰

• Skin eruptions at scabies infestation sites may worsen (increased lesion count and inflammation) during the first few days after initiation of treatment.^{80 87}

• Pruritus may persist 2–4 weeks after treatment while dead mites in the outer skin layers slough off with normal exfoliation.^{80 87}

• HIV-infected patients with uncomplicated scabies should receive the same treatment as those without HIV infection.¹⁰

• If used for treatment of Norwegian scabies†, multiple-dose regimen or use in conjunction with a topical scabicide is recommended to reduce risk of treatment failure.^{2 108 109} Immunocompromised patients, including those with HIV infection, are at increased risk of developing Norwegian scabies; such patients should be managed in consultation with an expert.¹⁰

Administration

Oral Administration

Administer orally.¹ Tablets should be taken on an empty stomach with water.¹

Dosage

Pediatric Patients

Safety and efficacy in children weighing <15 kg not established.¹

Ascariasis†

Ascaris lumbricoides infections†

Oral

150–200 mcg/kg as a single dose.³

Filariasis

Onchocerciasis (Filariasis Caused by Onchocerca volvulus)

Oral

Children weighing ≥15 kg: Approximately 150 mcg/kg as a single dose.¹

For individual patients, retreatment once every 6–12 months until asymptomatic;^{2 3} intervals as short as 3 months can be considered.¹

Approximate Single Dose for Treatment of Onchocerciasis (Based on Patient Weight) 1

Patient Weight (kg)	Single Oral Dose
15–25	3 mg
26–44	6 mg
45–64	9 mg
65–84	12 mg
≥85	150 mcg/kg

Alternatively, in some mass treatment and control programs, dosage is estimated based on height† since weighing recipients may be impractical (e.g., in rural areas of developing countries).^{80 86 88}

Approximate Single Dose for Treatment of Onchocerciasis in Mass Treatment Programs (Based on Patient Height†)8889

Patient Height (cm)	Single Oral Dose
90–119	3 mg
120–140	6 mg
141–158	9 mg
≥159	12 mg

Mansonella streptocerca Infections†

Oral

150 mcg/kg as a single dose.³

Wuchereria bancrofti Infections†

Oral

150–400 mcg/kg as a single dose has been used;^{63 64 65 66 76 77} often in conjunction with a single dose of albendazole or diethylcarbamazine.^{63 64 66 76 77}

Gnathostomiasis†

Gnathostoma spinigerum Infections†

Oral

200 mcg/kg once daily for 2 days.³

Hookworm Infections†

Cutaneous Larva Migrans (Creeping Eruption Caused by Dog and Cat Hookworms)†

Oral

200 mcg/kg once daily for 1–2 days.³

Strongyloidiasis

Treatment of Intestinal Strongyloides stercoralis Infections

Oral

Children weighing ≥15 kg: Approximately 200 mcg/kg as a single dose.¹ Alternatively, some clinicians recommend 200 mcg/kg once daily for 2 days.³

Manufacturer states that additional doses not generally necessary, but follow-up stool examinations necessary to verify eradication.¹ Retreat if recrudescence of larvae is observed.¹

Approximate Single Dose for Treatment of Intestinal Strongyloidiasis (Based on Patient Weight)1

Patient Weight (kg)	Single Oral Dose
15–24	3 mg
25–35	6 mg
36–50	9 mg
51–65	12 mg
66–79	15 mg
≥80	200 mcg/kg

Prevention of Strongyloides Hyperinfection in HSCT Candidates at Risk†

Oral

Children weighing ≥15 kg: 200 mcg/kg once daily for 2 days given prior to HSCT.⁹

In immunocompromised candidates, multiple courses at 2-week intervals may be required and cure may not be achievable.⁹

Trichuriasis†

Trichuris trichiura Infections†

Oral

200 mcg/kg once daily for 3 days.³

Pediculosis†

Pediculosis Capitis (Head Lice Infestation)†

Oral

200 mcg/kg once daily on days 1, 2, and 10.³

Alternatively, an initial 200-mcg/kg dose followed by an additional 200-mcg/kg dose given after 7–14 days.^{4 5 51 57 62}

Alternatively, an initial 300-mcg/kg dose followed by an additional 300-mcg/kg dose given after 7 days.⁸⁰

Pediculosis Pubis (Pubic Lice Infestation)†

Oral

200 mcg/kg as a single dose;³ an additional dose given after 10–14 days may be necessary in some patients.³

CDC recommends a 2-dose regimen using 250-mcg/kg doses given 2 weeks apart.¹⁰

Scabies†

Oral

200 mcg/kg as a single dose;^{3 46 68} an additional dose given after 10–14 days may be necessary in some patients.³

CDC recommends a 2-dose regimen using 200-mcg/kg doses given 2 weeks apart.¹⁰

Optimal number of doses has not been determined;¹⁰⁹ 2 doses usually recommended, especially in immunocompromised patients.^{3 4 5 10 32 46 47 51 52 60 108 109}

Crusted (Norwegian) Scabies†

Oral

Multiple-dose regimen consisting of 200-mcg/kg doses;^{10 52 108} some clinicians recommend doses be given once daily on days 1, 15, and 29.^{10 52}

Given with or without concomitant use of a topical scabicide (e.g., topical permethrin 5%).^{10 52 108}

Adults

Ascariasis†

Ascaris lumbricoides Infections†

Oral

150–200 mcg/kg as a single dose.³

Filariasis

Onchocerciasis (Filariasis Caused by Onchocerca volvulus)

Oral

Approximately 150 mcg/kg as a single dose.¹

For individual patients, retreatment once every 6–12 months until asymptomatic;^{2 3} intervals as short as 3 months can be considered.¹

Approximate Single Dose for Treatment of Onchocerciasis (Based on Patient Weight)1

Patient Weight (kg)	Single Oral Dose
15–25	3 mg
26–44	6 mg
45–64	9 mg
65–84	12 mg
≥85	150 mcg/kg

Alternatively, in some mass treatment and control programs, dosage is estimated based on height†; weighing recipients may be impractical (e.g., in rural areas of developing countries).^{80 86 88}

Approximate Single Dose for Treatment of Onchocerciasis in Mass Treatment Programs (Based on Patient Height†) 8889

Patient Height (cm)	Single Oral Dose
90–119	3 mg
120–140	6 mg
141–158	9 mg
≥159	12 mg

Mansonella Infections†

Oral

Filariasis caused by M. streptocerca†: 150 mcg/kg as a single dose.³

Filariasis caused by M. ozzardi†: 200 mcg/kg as a single dose has been used.³

Wuchereria bancrofti Infections†

Oral

150–400 mcg/kg as a single dose has been used;^{63 64 65 66 76 77} often in conjunction with a single dose of albendazole or diethylcarbamazine.^{63 64 66 76 77}

Gnathostomiasis†

Gnathostoma spinigerum Infections†

Oral

200 mcg/kg once daily for 2 days.³

Hookworm Infections†

Cutaneous Larva Migrans (Creeping Eruption Caused by Dog and Cat Hookworms)†

Oral

200 mcg/kg once daily for 1–2 days.³

Strongyloidiasis

Treatment of Intestinal Strongyloides stercoralis Infections

Oral

Approximately 200 mcg/kg as a single dose.¹ Alternatively, some clinicians recommend 200 mcg/kg once daily for 2 days.³

Manufacturer states that additional doses not generally necessary, but follow-up stool examinations necessary to verify eradication.¹ Retreat if recrudescence of larvae is observed.¹

Approximate Single Dose for Treatment of Intestinal Strongyloidiasis (Based on Patient Weight)1

Patient Weight (kg)	Single Oral Dose
15–24	3 mg
25–35	6 mg
36–50	9 mg
51–65	12 mg
66–79	15 mg
≥80	200 mcg/kg

Prevention of Strongyloides Hyperinfection in HSCT Candidates at Risk†

Oral

200 mcg/kg once daily given for 2 days prior to HSCT.⁹

In immunocompromised candidates, multiple courses at 2-week intervals may be required and cure may not be achievable.⁹

Trichuriasis†

Trichuris trichiura Infections†

Oral

200 mcg/kg once daily for 3 days.³

Pediculosis†

Pediculosis Capitis (Head Lice Infestation)†

Oral

200 mcg/kg once daily on days 1, 2, and 10.³

Alternatively, an initial 200-mcg/kg dose followed by an additional 200-mcg/kg dose given after 7–14 days.^{4 5 51 57 62}

Alternatively, an initial 300-mcg/kg dose followed by an additional 300-mcg/kg dose given after 7 days.⁸⁰

Pediculosis Pubis (Pubic Lice Infestation)†

Oral

200 mcg/kg as a single dose;³ an additional dose given after 10–14 days may be necessary in some patients.³

Alternatively, an initial 250-mcg/kg dose followed by an additional 250-mcg/kg dose after 7 days.⁸⁰

Scabies†

Oral

200 mcg/kg as a single dose.^{3 46 68}

Alternatively, 250–300 mcg/kg as a single dose.^{80 87}

A second dose may be required after 7–14 days, especially in immunocompromised patients.^{3 4 5 10 32 46 47 51 52 60}

Crusted (Norwegian) Scabies†

Oral

200 mcg/kg once daily on days 1, 15, and 29 recommended by CDC.¹⁰

Alternatively, 200 mcg/kg as a single dose in conjunction with a topical scabicide.^{10 52}

Cautions for Ivermectin

Contraindications

• Hypersensitivity to ivermectin or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

Mazzotti Reactions

Cutaneous and/or systemic reactions of varying severity (Mazzotti reactions) may occur in patients with onchocerciasis receiving microfilaricidal drugs (e.g., diethylcarbamazine, ivermectin).¹ These may be secondary to allergic and inflammatory responses to death of microfilariae.¹

Mazzotti reactions may include pruritus, edema, frank urticarial rash (papular and pustular), fever, arthralgia/synovitis, and lymph node enlargement/tenderness (e.g., axillary, cervical, inguinal).¹

Mazzotti-type reactions appear to be less severe and occur less frequently with ivermectin than with diethylcarbamazine.^{5 6 20 42}

These reactions may be most severe in previously untreated patients and may diminish with subsequent treatment (e.g., annual mass treatment and control programs).⁸⁰

Optimal treatment of severe Mazzotti reactions not determined.^{1 78} Oral or IV hydration, recumbency, and/or parenteral corticosteroids have been used to treat postural hypotension;¹ for supportive treatment of mild to moderate reactions, antihistamines, corticosteroids, and/or aspirin have been used.^{1 3}

Mazzotti-type reactions observed with treatment of onchocerciasis or the disease itself would not be anticipated in patients being treated for strongyloidiasis.¹

Ocular Effects

Ocular reactions (e.g., abnormal sensation in the eyes, eyelid edema, anterior uveitis, conjunctivitis, limbitis, keratitis, chorioretinitis or choroiditis) may occur in patients being treated for onchocerciasis or may occur secondary to the disease itself.¹

Ocular reactions observed with treatment of onchocerciasis or the disease itself would not be anticipated in patients being treated for strongyloidiasis.¹

Neurotoxicity

Not recommended in patients with an impaired blood-brain barrier (e.g., meningitis, African trypanosomiasis) or CNS disorders that may increase CNS penetration of the drug;^{2 4 13 91} potential interaction with CNS GABA receptors. (See Interactions.)^{2 4 13 91}

P-glycoprotein, encoded by the multi-drug resistance gene (MDR1), functions as a drug efflux transporter; appears to limit CNS uptake and prevent potentially fatal neurotoxicity.^{5 13 48 91 92}

Theoretical increased risk of neurotoxicity in patients with altered expression or function of p-glycoprotein (e.g. through genetic polymorphism, concomitant use of inhibitors of the p-glycoprotein transport system); if such increased susceptibility exists, apparently rare. (See Interactions.)^{5 48}

Although not reported in humans to date, neurotoxicity (e.g., tremors, ataxia, sweating, lethargy, coma, death) has occurred in certain animals with extreme sensitivity (e.g., collie dogs, inbred strains of mice);^{5 48 92} increased CNS sensitivity appears to be secondary to absent or dysfunctional MDR and p-glycoprotein.^{5 48 92}

General Precautions

Encephalopathy Risk in Onchocerciasis and Loiasis

Consider possible severe adverse effects when treating onchocerciasis in patients from areas where onchocerciasis and loiasis are co-endemic.^{3 16 54 78 79}

Patients with onchocerciasis who also are heavily infected with L. loa may develop serious or fatal neurologic events (e.g., encephalopathy, coma) either spontaneously or following rapid killing of microfilariae with effective microfilaricidal agents, including ivermectin.^{1 3 16 54 78 79}

Back pain, conjunctival hemorrhage, dyspnea, urinary and/or fecal incontinence, difficulty standing or walking, mental status changes, confusion, lethargy, stupor, seizures, coma, dysarthria or aphasia, fever, headache, or chills also reported.^{1 16 54 78}

Reported rarely in patients receiving ivermectin, but a definite causal relationship not established.^{1 54 93 94}

Pretreatment assessment for loiasis and careful post-treatment follow-up recommended when treatment is planned for any reason in patients with significant exposure to L. loa in endemic areas (West or Central Africa).^{1 16}

Other Precautions in Filariasis

Increased risk of severe adverse reactions (e.g., edema, aggravation of onchodermatitis) in patients with hyperreactive onchodermatitis (sowdah).¹

Does not kill adult O. volvulus worms, but decreases microfilarial load in skin for approximately 6–12 months following a single dose.^{1 2 8 11 18 20 80} Follow-up and retreatment required since the adult female worms continue to produce microfilaria for 9–15 years.^{5 7 19}

Specific Populations

Pregnancy

Category C.¹

Has been inadvertently given to pregnant women during mass distribution campaigns for treatment and control of onchocerciasis or lymphatic filariasis, but was not associated with adverse pregnancy outcomes, congenital malformations, or differences in developmental status or disease patterns in the offspring of such women.^{55 56 103 104}

WHO and other experts state that use for treatment of onchocerciasis after the first trimester probably is acceptable based on the high risk of infection-associated blindness if untreated.¹⁰⁴

Lactation

Distributed into milk.¹ Use in nursing women only when risk of delayed treatment in the woman outweighs risks to the nursing infant.^{1 104}

Pediatric Use

Safety and efficacy not established in children weighing <15 kg.¹

Some clinicians state that use not recommended in young children (e.g., those weighing <15 kg or <2 years of age) partly because the blood-brain barrier may be less developed than in older patients.^{5 95} (See Neurotoxicity under Cautions.)

Limited data suggest that safety in those 6–13 years of age similar to that in adults.¹

Geriatric Use

Insufficient experience in controlled clinical studies in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹ Other clinical experience has not revealed age-related differences in response.¹

Use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.¹

Common Adverse Effects

Treatment of onchocerciasis: Worsening of Mazzotti reactions (see Mazzotti Reactions under Cautions),¹ ocular effects,¹ peripheral edema,¹ tachycardia,¹ eosinophilia.¹

Treatment of strongyloidiasis: GI effects (diarrhea,¹ nausea,¹ anorexia,¹ constipation,¹ vomiting,¹ abdominal pain,¹ abdominal distention),¹ decreased leukocyte count,¹ eosinophilia,¹ increased hemoglobin,¹ increased serum ALT or AST,¹ nervous system effects (dizziness,¹ asthenia or fatigue,¹ somnolence,¹ tremor,¹ vertigo),¹ pruritus,¹ rash,¹ urticaria.¹

Interactions for Ivermectin

Appears to be metabolized by CYP3A4.⁴¹

Drugs with GABA-potentiating Activity

Concomitant use with drugs with GABA-potentiating activity (e.g., barbiturates, benzodiazepines, sodium oxybate, valproic acid) not recommended.^{13 80} Ivermectin may interact with GABA receptors in the CNS.^{2 4 13 91}

Inducers or Inhibitors of the p-glycoprotein Transport System

Ivermectin appears to be a substrate of p-glycoprotein transport system.^{13 40 48 80} Theoretical possibility of interactions with inducers (e.g., amprenavir, clotrimazole, phenothiazines, rifampin, ritonavir, St. John’s wort) or inhibitors (e.g., amiodarone, carvedilol, clarithromycin, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidine, ritonavir, tamoxifen, verapamil) of this system.^{13 40 48 80} Concomitant use with inhibitors theoretically could result in increased brain concentrations of ivermectin and neurotoxicity^{5 48}

Specific Drugs

Drug	Interaction	Comments
Alcohol	Increased plasma ivermectin concentrations13 43	Clinical importance unknown13 43
Anticoagulants	Excessive hypocoagulability reported with acenocoumarol (not commercially available in the US) after occupational contact with insecticide formulations of ivermectin (Epimek, not commercially available in the US) and metidation (Ultracid, not commercially available in the US)13 74	Clinical importance unknown13
Benzodiazepines	Benzodiazepine effects may be potentiated13	Concomitant use not recommended13

Ivermectin Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations attained in about 4 hours.^{1 6 14 35}

Food

High-fat meal may increase absorption, but effect of food on bioavailability not evaluated using usual dosage (150–200 mcg/kg).^{1 33}

Distribution

Extent

Concentrated in liver and adipose tissue.⁴²

Does not readily cross blood-brain barrier.^{1 5 48 91} Brain uptake apparently limited by p-glycoprotein transport system.^{5 13 48 91 92} (See Neurotoxicity under Cautions.)

Distributed into milk in low concentrations.¹

Plasma Protein Binding

Approximately 93%;⁷⁵ principally albumin and, to a lesser extent, α ₁-acid glycoprotein.³⁴

Elimination

Metabolism

Metabolized in the liver,¹ principally by CYP3A4.⁴¹

Appears to be a substrate of the p-glycoprotein transport system.^{40 48 49}

Elimination Route

Excreted principally in feces (within approximately 12 days); <1% excreted in urine.^{1 14 33 35 42}

Half-life

Approximately 18 hours following oral administration.^{1 33}

Stability

Storage

Oral

Tablets

≤30°C.¹

Actions and Spectrum

• An avermectin-derivative anthelmintic and anti-ectoparasitic;^{1 4 6 14 15 18 19 33 45} a macrocyclic lactone similar to macrolide antibacterials but possesses no antibacterial properties.^{14 20}

• In susceptible nematodes (roundworms), ivermectin affects ion channels in cell membranes.^{35 37 45}

• Binds selectively and with high affinity to glutamate-gated chloride ion channels in nerve and muscle cells of invertebrates, leading to increased cell membrane permeability to chloride ions; cellular hyperpolarization ensues, followed by paralysis and death.^{1 4 59}

• Also appears to interact with other ligand-gated chloride channels, such as those gated by GABA.^{1 4 5 14 59}

• In susceptible parasites, may interfere with the GI function resulting in starvation of the parasite.⁵

• Nematodes (roundworms): Active against tissue microfilariae of Onchocerca volvulus;^{1 2 4 6 8 14 19 20 32 35 36 45 53} intestinal stages of Strongyloides stercoralis (threadworm);^{1 2 3 4 6 8 19 20 32 35 37} microfilariae of Acylostoma braziliense,^{2 4 5 6 8 14 15 35 36} A. caninum,^{2 4 5 6 14 35 36} Brugia malayi,⁵³ Gnathostoma spinigerum,^{3 4} Loa loa,^{4 6 14 32 35 37 42 53} Mansonella streptocerca,^{3 21 22 42 45 53} M. ozzardi,^{3 22 35 42 53} and Wuchereria bancrofti;^{2 4 6 14 19 35 37 42 45 53} and intestinal stages of Ascaris lumbricoides^{6 19 35 36 37 45} and Enterobius vermicularis.^{20 35 37 45}

• Activity against Trichuris trichiura reported to be less than that against other nematodes.^{13 19 20 35 42 80} Has little or no activity against Ancylostoma duodenale,^{35 42} Mansonella perstans,^{22 35 42 45} Necator americanus,^{35 42} Toxocara canis,⁴ and T. catis.⁴

• Ectoparasites: Active against adult lice, including Pediculus humanus var capitis (head louse)^{2 5 8 32 35} and Phthirus pubis (pubic or crab louse)^{2 8} and active against the mite Sarcoptes scabiei.^{2 4 8 14 32 35} May also have some activity against Demodex mites.^{4 5}

• Resistance reported in some nematodes⁴ obtained from livestock after extensive exposure to ivermectin;⁶⁰ similar resistance not reported to date in nematodes obtained from humans.^{13 80}

• Although further study is needed, some data obtained from individuals in Ghana who received ivermectin in mass treatment programs of onchocerciasis (communities had received 6–18 rounds of treatment) suggest that ivermectin resistance in O. volvulus may be developing in some communities and is manifested as a more rapid return to high microfilarial load in the skin after treatment.¹¹⁰

• S. scabiei with reduced ivermectin susceptibility obtained from a few patients who received multiple doses (≥30 doses) for recurrent scabies episodes;⁵⁸ may represent inadequate dosage rather than actual resistance.⁸⁰

Advice to Patients

• Advise patients treated for onchocerciasis that the drug does not kill adult Onchocerca worms and that follow-up and retreatment usually is required.¹

• Advise patients treated for strongyloidiasis of the need for repeated stool examinations to document clearance of S. stercoralis infection.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant or past illnesses (e.g., meningitis, African trypanosomiasis, CNS disorders).¹

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

Ivermectin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	3 mg	Stromectol	Merck

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Stromectol 3MG Tablets (MERCK SHARP &amp; DOHME): 20/$111.17 or 60/$320.68