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Antinematodal AgentsEctoparasiticides, Including Scabicides
Antiparasitic agent in avermectin class; similar to macrolide antibiotics but lacks antibacterial activityUsed orally for onchocerciasis or strongyloidiasis and topically for Pediculus capitis (head lice) or rosaceaResistance to ivermectin has not been reported
Sklice, Soolantra, Stromectol
Ivermectin/Soolantra Topical Cream: 1%Ivermectin/Stromectol Oral Tab: 3mgSklice Topical Lotion: 0.5%
Doses should be prescribed to provide approximately 150 mcg/kg PO as a single dose. Alternatively, the manufacturer recommends the following dose using 3 mg tablets based on patient weight: 1 tablet for patients weighing 15—25 kg; 2 tablets for patients weighing 26—44 kg; 3 tablets for patients weighing 45—64 kg; 4 tablets for patients weighing 65—84 kg; and 150 mcg/kg for patients weighing >= 85 kg. Repeated follow-up and retreatment is usually required because ivermectin does not kill the adult onchocerca parasites. Retreatment intervals may be as short as 3 months. NOTE: Surgical removal of the subcutaneous nodules in which the adult parasites reside may be considered to ensure elimination of the parasite. Corticosteriods, antihistamines, or other antiinflammatory agents (i.e., aspirin) may be prescribed concurrently in serious infections to reduce the likelihood of a Mazzotti reaction. Patients with Onchocerca volvulus infection who may also be infected with Loa loa, may develop a severe or fatal encephalopathy. Careful pre- and post-treatment assessments are recommended when administering ivermectin to patients from Loa loa-endemic areas of West or Central Africa.
200 mcg/kg/dose PO once daily for 1 to 2 days. 
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 15 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 12 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 9 mg.
200 mcg/kg/dose PO once daily for 1 to 2 days.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 15 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 12 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 9 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 6 mg.
200 mcg/kg/dose once daily for 1 to 2 days. Usual dose: 3 mg.
Apply a sufficient amount of lotion (up to 1 tube) to thoroughly coat dry hair and. Leave on for 10 minutes then rinse off with water. A fine-tooth comb or special nit comb may be used to remove dead lice and nits. Wait 24 hours before applying shampoo to hair and scalp after use.
200 to 400 mcg/kg/dose PO for 2 doses, administered at least 7 days apart as an alternative.
250 mcg/kg/dose PO for 2 doses administered 2 weeks apart as an alternative.
200 to 400 mcg/kg/dose PO for 2 doses, administered at least 7 days apart as an alternative. In one study, a 3 dose regimen was administered at 7-day intervals.
Apply a pea-size amount to the affected areas of the face (forehead, chin, nose, each cheek) once daily. Spread as a thin layer, avoiding the eyes and lips.
The CDC recommends 200 mcg/kg PO as a single dose, with a repeat dose 2 weeks later as a first line option. Ivermectin has been effective in the mass treatment of scabies in an institutionalized setting.
The CDC recommends ivermectin oral dosing along with the use of a topical scabicide. Ivermectin (200 mcg/kg PO with food) is given as five doses (approximately days 1, 2, 8, 9, and 15), with consideration of two additional doses (approximately days 22 and 29) for severe infestations. A full body application (all body parts from neck down) of permethrin 5% cream topically daily for 7 days and then 2 times weekly until release from care or cure is preferred for topical application. A topical keratolytic cream may also be used to help reduce the crusting of the skin. Re-treatment 2 weeks after the initial treatment regimen can be considered for those persons who are still symptomatic or when live mites are observed. Use of an alternative regimen is recommended for those persons who do not respond initially to the recommended treatment. Optimal regimens are not yet determined. Topical benzyl benzoate 5% may be used as an alternative agent to permethrin but is likely to cause skin irritation.
300 mcg/kg PO as a single dose or given annually for treatment in endemic areas.
150 mcg/kg PO as a single dose. A second and occasionally a third dose of ivermectin, each dose one week apart, is necessary if pruritis persists or if the larva continues to migrate 1 week after the previous dose.
†Indicates off-label use
150—200 mcg/kg single dose PO for most indications; up to 400 mcg/kg PO for Bancroft's filariasis; 4 oz/topical application.
150—200 mcg/kg single dose PO for most indications; 4 oz/topical application.
> 15 kg: 150—200 mcg/kg single dose PO for most indications; 4 oz/topical application.<= 15 kg: Safety and efficacy have not been established for oral dosage forms; 4 oz/topical application.
>= 6 months: Safety and efficacy have not been established for oral dosage forms; 4 oz/topical application.< 6 months: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Patients with abnormal liver tests prior to beginning ivermectin therapy should be carefully evaluated.
The pharmacokinetics of ivermectin in patients with renal impairment has not been studied; however, renal elimination of this drug is negligible and dosage adjustment in renal impairment is not expected to be necessary.
Administer ivermectin tablets on an empty stomach with water.
Ivermectin lotionIvermectin lotion is administered topically for head lice. Avoid contact with eyes, mouth, or any mucus membrane. Do not ingest.Scalp and hair should be dry prior to application.Apply a sufficient amount to thoroughly cover scalp and hair (up to the full contents of 1 tube).Leave on for 10 minutes, and then rinse with only water.Wash hands after use.Wait 24 hours before applying shampoo to hair and scalp after use.The tube is for single use only; discard any unused portion.For proper treatment of pediculosis, wash in hot water or dry clean all recently worn clothing, hats, used bedding and towels, and wash personal care items such as combs, brushes, and hair clips in hot water. Ivermectin creamIvermectin cream is administered topically for rosacea. Avoid contact with eyes and lips.It is not for oral, ophthalmic, or intravaginal use.Apply to the affected areas of the face.
Sklice:- Discard unused portion. Do not store for later use.- Do not freeze- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees FSoolantra:- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees FStromectol:- Store below 86 degrees F
Ivermectin is not an antiviral drug and is not FDA-approved for treating or preventing COVID-19. Off-label use of any drug can cause serious harm. Ivermectin intended for veterinary use in animals has not been evaluated for use in humans. Animal products are often highly concentrated and such high doses can be toxic in humans. Do not use veterinary ivermectin products as substitutes for FDA-approved human ivermectin products prescribed by a health care provider for appropriate indications. Ivermectin is contraindicated in patients with hypersensitivity to any component of the product.
Patients with a history of severe asthma should receive ivermectin with caution. Occasionally, systemic ivermectin has been reported to worsen bronchial asthma.
Although not extensively studied, due to its extensive hepatic metabolism, ivermectin should be administered with caution in patients with significant hepatic disease.
In patients with immunosuppression (including those with human immunodeficiency virus (HIV) infection) treated for intestinal strongyloidiasis, repeated ivermectin courses may be necessary. Adequate and well-controlled clinical studies have not been conducted in such patients to determine the optimal dosing regimen. Several treatments (i.e., at 2 week intervals) may be required and a cure may not be achievable. Control of extra-intestinal strongyloidiasis in these patients is difficult, however, suppressive therapy (i.e., once per month) may be helpful.
Data with oral ivermectin use during pregnancy are insufficient to inform a drug-associated risk. Systemic exposure from topical use of ivermectin is much lower than from oral use. Four published epidemiology studies evaluated the outcomes of a total of 744 women exposed to oral ivermectin in various stages of pregnancy. In the largest study, 397 women in the second trimester of pregnancy were treated open-label with single doses of ivermectin or ivermectin plus albendazole; there was no observed difference in pregnancy outcomes between treated and untreated populations. However, these studies cannot definitely establish or exclude the absence of drug-associated risk during pregnancy, because either the timing of the administration during gestation was not accurately ascertained or the administration only occurred during the second trimester. In animal embyrofetal development studies of oral ivermectin given during organogenesis, adverse developmental outcomes, including cleft palate, exencephaly, wavy ribs, and clubbed forepaws, occurred at or near doses that were maternally toxic. Pre-implantation loss and abortion were also noted.
After oral administration, ivermectin is excreted in human breast milk in low concentrations. Excretion in human breast milk after topical administration has not been evaluated. According to the manufacturer, treatment with oral ivermectin in mothers who are breast-feeding should only be undertaken when the risk of delayed treatment to the mother outweighs the possible risk to the newborn. Previous American Academy of Pediatrics (AAP) recommendations considered oral ivermectin to be usually compatible with breast-feeding. The amount of ivermectin present in human milk after topical application has not been studied; however, systemic exposure from topical ivermectin use is much lower than from oral use. According to the manufacturer, discontinue nursing or discontinue the topical cream, taking into account the importance of the drug to the mother. Women who are breast-feeding while using topical ivermectin should avoid accidental transfer of ivermectin to the breast area where it might be directly ingested while nursing.
The topical administration of ivermectin to infants and children should be under the direct supervision of an adult to prevent ingestion of the lotion.
Rarely, patients with onchocerciasis and Loa loa coinfection may develop a serious or even fatal encephalopathy either spontaneously or after treatment with an effective microfilaricide. This syndrome has been seen very rarely after the use of ivermectin. In individuals who warrant treatment with ivermectin for any reason and have had significant exposure to Loa loa-endemic areas of West and Central Africa, pretreatment assessment for loiasis and careful posttreatment follow-up is recommended.
Patients with hyperreactive onchodermatitis (i.e., sowda) may be more likely than others to experience severe edema and worsening of onchodermatitis after ivermectin use.
angioedema / Rapid / 1.2-1.2Stevens-Johnson syndrome / Delayed / 0-1.0toxic epidermal necrolysis / Delayed / 0-1.0seizures / Delayed / 0-1.0ocular hemorrhage / Delayed / 0-1.0coma / Early / 0-1.0uveitis / Delayed / Incidence not knownvisual impairment / Early / Incidence not knownkeratitis / Delayed / Incidence not known
lymphadenopathy / Delayed / 3.0-13.9synovitis / Delayed / 9.3-9.3sinus tachycardia / Rapid / 3.5-3.5peripheral edema / Delayed / 3.2-3.2eosinophilia / Delayed / 3.0-3.0elevated hepatic enzymes / Delayed / 2.0-2.0orthostatic hypotension / Delayed / 1.1-1.1conjunctivitis / Delayed / 0-1.0hyperbilirubinemia / Delayed / 0-1.0hepatitis / Delayed / 0-1.0dyspnea / Early / 0-1.0fecal incontinence / Early / 0-1.0confusion / Early / 0-1.0urinary incontinence / Early / 0-1.0encephalopathy / Delayed / 0-1.0leukopenia / Delayed / 0-1.0anemia / Delayed / 0-1.0constipation / Delayed / 0.9-0.9edema / Delayed / Incidence not knowncontact dermatitis / Delayed / Incidence not knownprolonged bleeding time / Delayed / Incidence not known
pruritus / Rapid / 2.8-27.5urticaria / Rapid / 0.9-22.7fever / Early / 22.6-22.6arthralgia / Delayed / 9.3-9.3dizziness / Early / 2.8-2.8diarrhea / Early / 1.8-1.8nausea / Early / 1.8-1.8xerosis / Delayed / 0-1.0skin irritation / Early / 0-1.0ocular irritation / Rapid / 0-1.0back pain / Delayed / 0-1.0lethargy / Early / 0-1.0rash / Early / 0.9-0.9asthenia / Delayed / 0.9-0.9fatigue / Early / 0.9-0.9vomiting / Early / 0.9-0.9anorexia / Delayed / 0.9-0.9abdominal pain / Early / 0.9-0.9vertigo / Early / 0.9-0.9tremor / Early / 0.9-0.9drowsiness / Early / 0.9-0.9maculopapular rash / Early / Incidence not known
Aprepitant, Fosaprepitant: (Moderate) Use caution if ivermectin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ivermectin-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ivermectin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ivermectin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Boceprevir: (Moderate) Close clinical monitoring is advised when administering ivermectin with boceprevir due to an increased potential for ivermectin-related adverse events. If ivermectin dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ivermectin. Ivermectin is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ivermectin plasma concentrations. Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ivermectin, a CYP3A substrate, as ivermectin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as ivermectin may be increased when co-administered with mirabegron. Ivermectin has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary. Mitotane: (Moderate) Use caution if mitotane and ivermectin are used concomitantly, and monitor for decreased efficacy of ivermectin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and ivermectin is a CYP3A4 substrate. Coadministration may result in decreased plasma concentrations of ivermectin; however, ivermectin is administered as a single dose, and significant clinical interactions are not expected. Posaconazole: (Moderate) Posaconazole and ivermectin should be coadministered with caution due to an increased potential for ivermectin-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ivermectin. These drugs used in combination may result in elevated ivermectin plasma concentrations, causing an increased risk for ivermectin-related adverse events. Telaprevir: (Moderate) Close clinical monitoring is advised when administering ivermectin with telaprevir due to an increased potential for ivermectin-related adverse events. If ivermectin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ivermectin. Ivermectin is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ivermectin plasma concentrations. Warfarin: (Moderate) Concurrent administration of warfarin and oral ivermectin has been associated with postmarketing reports of elevated INR. In 1 case report, a patient who was previously stable on warfarin developed supratherapeutic INR concentrations (greater than 20) and subsequent hematoma after receiving two 3 mg oral ivermectin doses. Although data are limited, ivermectin has been shown to antagonize vitamin K-dependent clotting factors II, VII, IX, and X.
Avermectins, including ivermectin, are broad-spectrum antiparasitic agents. They bind selectively and with high affinity to glutamate-gated chloride ion channels present in invertebrate nerve and muscle cells. This binding 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. This class of compounds may also bind with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA). The avermectins' selectivity is due to the fact that some mammals do not have glutamate-gated chloride channels and that the avermectins have a low affinity for mammalian ligand-gated chloride channels. Ivermectin does not cross the blood-brain barrier in humans.
Ivermectin is administered orally and topically. Affected cytochrome P450 isoenzymes: CYP3A4, CYP2D6, CYP2E1Ivermectin is hepatically metabolized. It is primarily metabolized by cytochrome P450 3A4, and theoretically the metabolism may be affected by inducers and inhibitors of this enzyme. However, ivermectin is administered as a single dose, and significant clinical interactions are not expected. Depending on the in vitro method used, the CYP2D6 and CYP2E1 isoenzymes may also be involved in metabolism but to a significantly lower extent than CYP3A4. In vitro studies using human liver microsomes suggest that ivermectin does not significantly inhibit the CYP3A4, CYP2D6, CYP2C9, CYP1A2, or CYP2E1 isoenzymes. Ivermectin and its inactive metabolites are excreted almost exclusively in the feces over 12 days. Less than 1% of the dose is excreted in the urine. The plasma half life is reported as 16 to 28 hours, the volume of distribution is 46.9 L, and clearance is 1.2 L/h after oral administration.
Following oral administration, ivermectin is well absorbed with plasma concentrations proportional to the dose. The effect of food on the absorption of ivermectin has not been determined, therefore the drug is recommended to be taken on an empty stomach with water.
Ivermectin lotionAfter a single application of ivermectin lotion, systemic concentrations are much lower than those observed after oral administration of ivermectin at a dose of 165 mcg/kg PO. The mean Cmax and AUC from time zero to the time of last measurable concentration were 0.24 +/- 0.23 ng/mL and 6.7 +/- 11.2 hour x ng/mL, respectively. Ivermectin creamAfter 2 weeks of treatment with ivermectin cream, the Tmax was 10 +/- 8 hours, the Cmax was 2.1 +/- 1.04 ng/mL and AUC was 36.15 +/- 15.56 ng x hour/mL. At the end of the 52-week treatment period, there was no plasma accumulation of ivermectin. The terminal half-life was 6.5 days (155 +/- 40 hours) in patients receiving a once daily cutaneous application of ivermectin cream for 28 days.