Stromectol

Antinematodal Agents
Ectoparasiticides, Including Scabicides

Administer ivermectin tablets on an empty stomach with water.

Ivermectin lotion
Ivermectin 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 cream
Ivermectin 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.

angioedema / Rapid / 1.2-1.2
Stevens-Johnson syndrome / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
ocular hemorrhage / Delayed / 0-1.0
seizures / Delayed / Incidence not known
uveitis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
keratitis / Delayed / Incidence not known
coma / Early / Incidence not known

lymphadenopathy / Delayed / 3.0-13.9
synovitis / Delayed / 9.3-9.3
sinus tachycardia / Rapid / 3.5-3.5
peripheral edema / Delayed / 3.2-3.2
eosinophilia / Delayed / 3.0-3.0
elevated hepatic enzymes / Delayed / 2.0-2.0
orthostatic hypotension / Delayed / 1.1-1.1
conjunctivitis / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
anemia / Delayed / 0-1.0
constipation / Delayed / 0.9-0.9
edema / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
dyspnea / Early / Incidence not known
neurotoxicity / Early / Incidence not known
confusion / Early / Incidence not known
urinary incontinence / Early / Incidence not known
loss of consciousness / Rapid / Incidence not known
fecal incontinence / Early / Incidence not known
prolonged bleeding time / Delayed / Incidence not known

pruritus / Rapid / 2.8-27.5
urticaria / Rapid / 0.9-22.7
fever / Early / 22.6-22.6
arthralgia / Delayed / 9.3-9.3
dizziness / Early / 2.8-2.8
diarrhea / Early / 1.8-1.8
nausea / Early / 1.8-1.8
xerosis / Delayed / 0-1.0
skin irritation / Early / 0-1.0
ocular irritation / Rapid / 0-1.0
rash / Early / 0.9-0.9
asthenia / Delayed / 0.9-0.9
fatigue / Early / 0.9-0.9
vomiting / Early / 0.9-0.9
anorexia / Delayed / 0.9-0.9
abdominal pain / Early / 0.9-0.9
drowsiness / Early / 0.9-0.9
vertigo / Early / 0.9-0.9
tremor / Early / 0.9-0.9
maculopapular rash / Early / Incidence not known
lethargy / Early / Incidence not known
back pain / Delayed / Incidence not known

Sklice, Soolantra, Stromectol

Rx, OTC

Antiparasitic agent in avermectin class; similar to macrolide antibiotics but lacks antibacterial activity
Used orally for onchocerciasis or strongyloidiasis and topically for Pediculus capitis (head lice) or rosacea
Resistance to ivermectin has not been reported

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.[34399] [64719]

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.

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.

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 7 to 14 days 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.

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. 

200 mcg/kg/dose 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.

1% lotion applied to all areas of the body from the neck down and washed off after 8 to 14 hours; repeat treatment in 1 week if symptoms persist.

200 mcg/kg/dose PO 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 along with use of a topical scabicide (5% topical permethrin cream or 25% topical benzyl benzoate). Retreatment 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.

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.

150 to 200 mcg/kg/dose PO as a single dose.

150 to 200 mcg/kg/dose PO as a single dose.

200 mcg/kg/dose PO as a single dose; repeat dose in 2 weeks.

200 mcg/kg/dose PO as a single dose; repeat dose in 2 weeks.

200 mcg/kg/dose PO once daily for 3 days.

200 mcg/kg/dose PO once daily for 3 days.

†Indicates off-label use

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.

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.
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.
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.

Ivermectin/Sklice Topical Lotion: 0.5%
Ivermectin/Soolantra Topical Cream: 1%
Ivermectin/Stromectol Oral Tab: 3mg

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.

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.

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, CYP2E1
Ivermectin 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 lotion
After 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 cream
After 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.

Available data on the use of oral and topical ivermectin during pregnancy are insufficient to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal. Four published epidemiology studies evaluated the outcomes of a total of 744 patients exposed to oral ivermectin in various stages of pregnancy. In the largest study, 397 patients 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; however, there is insufficient information to determine the effects of ivermectin on the breast-fed infant or on milk production. 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 presence of ivermectin in human milk after topical application has not been studied; however, systemic exposure from topical ivermectin use is much lower than from oral use. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for topical ivermectin and any potential adverse effects on the breast-fed infant from exposure to the drug or from the underlying maternal condition. 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.