Ivermectin (oral)

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Ivermectin (oral)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

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Overview

Ivermectin (oral) is a anthelmintic and anti-infective agent that is FDA approved for the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis and onchocerciasis due to the nematode parasite Onchocerca volvulus.. Common adverse reactions include fatigue, abdominal pain, anorexia, constipation, diarrhea, nausea, vomiting, dizziness, somnolence, vertigo, tremor, pruritus, rash and urticaria..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Ivermectin is indicated for the treatment of the following infections:
  • This indication is based on clinical studies of both comparative and open-label designs, in which 64-100% of infected patients were cured following a single 200-mcg/kg dose of Ivermectin.
Dosing Information
  • The recommended dosage of Ivermectin for the treatment of strongyloidiasis is a single oral dose designed to provide approximately 200 mcg of Ivermectin per kg of body weight. See Table 1 for dosage guidelines. Patients should take tablets on an empty stomach with water. In general, additional doses are not necessary. However, follow-up stool examinations should be performed to verify eradication of infection.
This image is provided by the National Library of Medicine.
Onchocerciasis
  • The recommended dosage of Ivermectin for the treatment of onchocerciasis is a single oral dose designed to provide approximately 150 mcg of Ivermectin per kg of body weight. See Table 2 for dosage guidelines. Patients should take tablets on an empty stomach with water. In mass distribution campaigns in international treatment programs, the most commonly used dose interval is 12 months. For the treatment of individual patients, retreatment may be considered at intervals as short as 3 months.
This image is provided by the National Library of Medicine.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

  • Dosing Information
    • 50 to 200 micrograms/kilogram

Non–Guideline-Supported Use

  • Dosing Information
    • 50 to 200 micrograms/kilogram [1]
  • Dosing Information
    • PO single dose of 200 µg/per kg [2]
  • Dosing Information
    • PO 50 to 200 micrograms/kg
  • Dosing Information
    • PO single dose single dose of 300 micrograms/kg
  • Dosing Information
    • 25 to 200 micrograms/kg, oral for 5 to 10 days
  • Dosing Information
    • PO single dose of 6 mg
  • Dosing Information
    • 200 mcg/kg PO and then repeat it within 2 weeks

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Ivermectin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ivermectin in pediatric patients.

Non–Guideline-Supported Use

  • Dosing Information
    • 50 to 200 micrograms/kilogram [1]

Contraindications

  • Ivermectin is contraindicated in patients who are hypersensitive to any component of this product.

Warnings

  • Historical data have shown that microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions in patients with onchocerciasis. These reactions are probably due to allergic and inflammatory responses to the death of microfilariae. Patients treated with Ivermectin for onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, probably, or definitely related to the drug itself.
PRECAUTIONS
  • General
  • After treatment with microfilaricidal drugs, patients with hyperreactive onchodermatitis (sowda) may be more likely than others to experience severe adverse reactions, especially edema and aggravation of onchodermatitis.

Adverse Reactions

Clinical Trials Experience

Strongyloidiasis
  • In four clinical studies involving a total of 109 patients given either one or two doses of 170 to 200 mcg/kg of Ivermectin, the following adverse reactions were reported as possibly, probably, or definitely related to Ivermectin:
Body as a Whole:
Gastrointestinal:
Nervous System/Psychiatric:
Skin:
Laboratory Test Findings
  • In clinical trials involving 109 patients given either one or two doses of 170 to 200 mcg/kg Ivermectin, the following laboratory abnormalities were seen regardless of drug relationship: elevation in ALT and/or AST (2%), decrease in leukocyte count (3%). Leukopenia and anemia were seen in one patient.
Onchocerciasis
  • In clinical trials, ophthalmological conditions were examined in 963 adult patients before treatment, at day 3, and months 3 and 6 after treatment with 100 to 200 mcg/kg Ivermectin. Changes observed were primarily deterioration from baseline 3 days post-treatment. Most changes either returned to baseline condition or improved over baseline severity at the month 3 and 6 visits. The percentages of patients with worsening of the following conditions at day 3, month 3 and 6, respectively, were: limbitis: 5.5%, 4.8%, and 3.5% and punctate opacity: 1.8%, 1.8%, and 1.4%. The corresponding percentages for patients treated with placebo were: limbitis: 6.2%, 9.9%, and 9.4% and punctate opacity: 2.0%, 6.4%, and 7.2%.
  • In clinical trials involving 963 adult patients who received 100 to 200 mcg/kg Ivermectin, the following clinical adverse reactions were reported as possibly, probably, or definitely related to the drug in ≥1% of the patients: facial edema (1.2%), peripheral edema (3.2%), orthostatic hypotension (1.1%), and tachycardia (3.5%). Drug-related headache and myalgia occurred in <1% of patients (0.2% and 0.4%, respectively). However, these were the most common adverse experiences reported overall during these trials regardless of causality (22.3% and 19.7%, respectively).
  • A similar safety profile was observed in an open study in pediatric patients ages 6 to 13.
Laboratory Test Findings
  • In controlled clinical trials, the following laboratory adverse experiences were reported as possibly, probably, or definitely related to the drug in ≥1% of the patients: eosinophilia (3%) and hemoglobin increase (1%).

Postmarketing Experience

  • The following adverse reactions have been reported since the drug was registered overseas:
Onchocerciasis
All Indications

Drug Interactions

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • Ivermectin has been shown to be teratogenic in mice, rats, and rabbits when given in repeated doses of 0.2, 8.1, and 4.5 times the maximum recommended human dose, respectively (on a mg/m2/day basis). Teratogenicity was characterized in the three species tested by cleft palate; clubbed forepaws were additionally observed in rabbits. These developmental effects were found only at or near doses that were maternotoxic to the pregnant female. Therefore, Ivermectin does not appear to be selectively fetotoxic to the developing fetus. There are, however, no adequate and well-controlled studies in pregnant women. Ivermectin should not be used during pregnancy since safety in pregnancy has not been established.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ivermectin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Ivermectin during labor and delivery.

Nursing Mothers

  • Ivermectin is excreted in human milk in low concentrations. Treatment of mothers who intend to breast-feed should only be undertaken when the risk of delayed treatment to the mother outweighs the possible risk to the newborn.

Pediatric Use

  • Safety and effectiveness in pediatric patients weighing less than 15 kg have not been established.

Geriatic Use

  • Clinical studies of Ivermectin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, treatment of an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Gender

There is no FDA guidance on the use of Ivermectin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Ivermectin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Ivermectin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Ivermectin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Ivermectin in women of reproductive potentials and males.

Immunocompromised Patients

  • In immunocompromised (including HIV-infected) patients being treated for intestinal strongyloidiasis, repeated courses of therapy may be required. 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 cure may not be achievable. Control of extra-intestinal strongyloidiasis in these patients is difficult, and suppressive therapy, i.e., once per month, may be helpful.

Administration and Monitoring

Administration

Monitoring

There is limited information regarding Monitoring of Ivermectin in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Ivermectin in the drug label.

Overdosage

  • Significant [[lethal|lethality]] was observed in mice and rats after single oral doses of 25 to 50 mg/kg and 40 to 50 mg/kg, respectively. No significant lethality was observed in dogs after single oral doses of up to 10 mg/kg. At these doses, the treatment-related signs that were observed in these animals include ataxia, bradypnea, tremors, ptosis, decreased activity, emesis, and mydriasis.

Pharmacology

Template:Px
Ivermectin (oral)
Systematic (IUPAC) name
22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b
Identifiers
CAS number 70288-86-7
71827-03-7
ATC code P02CF01 Template:ATCvet Template:ATCvet
PubChem 9812710
DrugBank APRD01058
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 875.10 g/mol
Pharmacokinetic data
Bioavailability ?
Protein binding 93%
Metabolism Liver (CYP450)
Half life 18 hours
Excretion Feces; <1% urine
Therapeutic considerations
Pregnancy cat.

B3(AU) C(US)

Legal status

[[Prescription drug|Template:Unicode-only]](US)

Routes Oral, topical

Mechanism of Action

Microbiology

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

Structure

  • Ivermectin is a semisynthetic, anthelmintic agent for oral administration. Ivermectin is derived from the avermectins, a class of highly active broad-spectrum, anti-parasitic agents isolated from the fermentation products of Streptomyces avermitilis. Ivermectin is a mixture containing at least 90% 5-O-demethyl-22,23-dihydroavermectin A1a and less than 10% 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-methylethyl)avermectin A1a, generally referred to as 22,23-dihydroavermectin B1a and B1b, or H2B1a and H2B1b, respectively. The respective empirical formulas are C48H74O14 and C47H72O14, with molecular weights of 875.10 and 861.07, respectively. The structural formulas are:
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Ivermectin in the drug label.

Pharmacokinetics

  • Following oral administration of Ivermectin, plasma concentrations are approximately proportional to the dose. In two studies, after single 12-mg doses of Ivermectin in fasting healthy volunteers (representing a mean dose of 165 mcg/kg), the mean peak plasma concentrations of the major component (H2B1a) were 46.6 (±21.9) (range: 16.4-101.1) and 30.6 (±15.6) (range: 13.9-68.4) ng/mL, respectively, at approximately 4 hours after dosing. Ivermectin is metabolized in the liver, and Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. The plasma half-life of Ivermectin in man is approximately 18 hours following oral administration.
  • The safety and pharmacokinetic properties of Ivermectin were further assessed in a multiple-dose clinical pharmacokinetic study involving healthy volunteers. Subjects received oral doses of 30 to 120 mg (333 to 2000 mcg/kg) Ivermectin in a fasted state or 30 mg (333 to 600 mcg/kg) Ivermectin following a standard high-fat (48.6 g of fat) meal. Administration of 30 mg Ivermectin following a high-fat meal resulted in an approximate 2.5-fold increase in bioavailability relative to administration of 30 mg Ivermectin in the fasted state.
  • In vitro studies using human liver microsomes and recombinant CYP450 enzymes have shown that Ivermectin is primarily metabolized by CYP3A4. Depending on the in vitro method used, CYP2D6 and CYP2E1 were also shown to be involved in the metabolism of Ivermectin but to a significantly lower extent compared to CYP3A4. The findings of in vitro studies using human liver microsomes suggest that clinically relevant concentrations of Ivermectin do not significantly inhibit the metabolizing activities of CYP3A4, CYP2D6, CYP2C9, CYP1A2, and CYP2E1.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Ivermectin in the drug label.

Clinical Studies

Strongyloidiasis]]=

  • Two controlled clinical studies using albendazole as the comparative agent were carried out in international sites where albendazole is approved for the treatment of strongyloidiasis of the gastrointestinal tract, and three controlled studies were carried out in the U.S. and internationally using thiabendazole as the comparative agent. Efficacy, as measured by cure rate, was defined as the absence of larvae in at least two follow-up stool examinations 3 to 4 weeks post-therapy. Based on this criterion, efficacy was significantly greater for Ivermectin (a single dose of 170 to 200 mcg/kg) than for albendazole (200 mg b.i.d. for 3 days). Ivermectin administered as a single dose of 200 mcg/kg for 1 day was as efficacious as thiabendazole administered at 25 mg/kg b.i.d. for 3 days.
This image is provided by the National Library of Medicine.
  • In one study conducted in France, a non-endemic area where there was no possibility of reinfection, several patients were observed to have recrudescence of Strongyloides larvae in their stool as long as 106 days following Ivermectin therapy. Therefore, at least three stool examinations should be conducted over the three months following treatment to ensure eradication. If recrudescence of larvae is observed, retreatment with Ivermectin is indicated. Concentration techniques (such as using a Baermann apparatus) should be employed when performing these stool examinations, as the number of Strongyloides larvae per gram of feces may be very low.
Onchocerciasis
  • The evaluation of Ivermectin in the treatment of onchocerciasis is based on the results of clinical studies involving 1278 patients. In a double-blind, placebo-controlled study involving adult patients with moderate to severe onchocercal infection, patients who received a single dose of 150 mcg/kg Ivermectin experienced an 83.2% and 99.5% decrease in skin microfilariae count (geometric mean) 3 days and 3 months after the dose, respectively. A marked reduction of >90% was maintained for up to 12 months after the single dose. As with other microfilaricidal drugs, there was an increase in the microfilariae count in the anterior chamber of the eye at day 3 after treatment in some patients. However, at 3 and 6 months after the dose, a significantly greater percentage of patients treated with Ivermectin had decreases in microfilariae count in the anterior chamber than patients treated with placebo.
  • In a separate open study involving pediatric patients ages 6 to 13 (n=103; weight range: 17-41 kg), similar decreases in skin microfilariae counts were observed for up to 12 months after dosing.
Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Ivermectin.
  • Ivermectin was not genotoxic in vitro in the Ames microbial mutagenicity assay of Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100 with and without rat liver enzyme activation, the Mouse Lymphoma Cell Line L5178Y (cytotoxicity and mutagenicity) assays, or the unscheduled DNA synthesis assay in human fibroblasts.
  • Ivermectin had no adverse effects on the fertility in rats in studies at repeated doses of up to 3 times the maximum recommended human dose of 200 mcg/kg (on a mg/m2/day basis).

How Supplied

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

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

Dist. by: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: Merck Sharp & Dohme BV Waarderweg 39 2031 BN Haarlem Netherlands

Issued May 2010

Printed in the Netherlands

9032319

87447/080610

8495

Storage

  • Store at temperatures below 30°C (86°F).

Images

Drug Images

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Package and Label Display Panel

Stromectol® 3 mg (Ivermectin Tablets)

Manuf. by: Merck Sharp & Dohme BV Waarderweg 39 2031 BN Haarlem, Netherlands

Formulated in Netherlands

Dist. by: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC. Whitehouse Station, NJ 08889, USA

Each tablet contains 3 mg of Ivermectin.

USUAL DOSAGE: See accompanying circular.

Store at temperatures below 30°C (86°F).

Rx only

20 Tablets (2 Foil Strips of 10 tablets each)

NDC 0006-0032-20

This is a bulk package and not intended for dispensing. The aluminum foil strip is not child resistant. Remove tablets from aluminum foil strip and dispense tablets in appropriate container.

20 {{#ask: Label Page::Ivermectin (oral) |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

  • Ivermectin should be taken on an empty stomach with water.
  • Strongyloidiasis: The patient should be reminded of the need for repeated stool examinations to document clearance of infection with Strongyloides stercoralis.
  • onchocerciasis: The patient should be reminded that treatment with Ivermectin does not kill the adult Onchocerca parasites, and therefore repeated follow-up and retreatment is usually required.

Precautions with Alcohol

  • Alcohol-Ivermectin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Stromectol®
  • Sklice®

Look-Alike Drug Names

There is limited information regarding Ivermectin (oral) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ 1.0 1.1 Marti H, Haji HJ, Savioli L, Chwaya HM, Mgeni AF, Ameir JS; et al. (1996). "A comparative trial of a single-dose ivermectin versus three days of albendazole for treatment of Strongyloides stercoralis and other soil-transmitted helminth infections in children". Am J Trop Med Hyg. 55 (5): 477–81. PMID 8940976.
  2. ↑ Bouchaud O, Houzé S, Schiemann R, Durand R, Ralaimazava P, Ruggeri C; et al. (2000). "Cutaneous larva migrans in travelers: a prospective study, with assessment of therapy with ivermectin". Clin Infect Dis. 31 (2): 493–8. doi:10.1086/313942. PMID 10987711.

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