Generic Name: Ivermectin
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 B1a (C48H74O14) and Ivermectin Component B1b (C47H72O14)
CAS Number: 70288-86-7
Introduction
Anthelmintic and anti-ectoparasitic agent; avermectin derivative.1 4 6 14 15 18 19 33 45
Uses for Stromectol
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
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 ivermectin15 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 patients3 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
Stromectol 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 Stromectol
Contraindications
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 Stromectol
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 neurotoxicity5 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
|
Stromectol 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
