Vermectin

Tablet: White, round flat bevel-edge tablet contains "IV'', "6'' and scored on one side with "ATC in a triangle" on the other side.
Each tablet contains Ivermectin 6 mg.
Solution for injection: Clear colorless solution.
Each ml contains ivermectin 10 mg.

Pharmacology: Pharmacodynamics: Ivermectin is a semisynthetic anthelminthic agent; it binds selectively and with strong affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to increased permeability of cell membranes to chloride ions then hyperpolarization of the nerve or muscle cell, and death of the parasite.
Pharmacokinetics: Tablet: Absorption: Well absorbed.
Distribution: V_d: 3.1 to 3.5 L/kg (healthy males); high concentration in the liver and adipose tissue; does not readily cross the blood-brain barrier.
Protein binding: ~93% primarily to albumin.
Metabolism: Hepatic via CYP3A4 (major), CYP2D6 (minor), and CYP2E1 (minor).
Half-life elimination: 18 hours.
Time to peak, serum: ~4 hours.
Excretion: Feces; urine (<1%).
Half-life elimination: 18 hours.
Time to peak, serum: ~4 hours.
Solution for injection: There are no pharmacokinetic data on subcutaneous ivermectin in humans but the kinetics have been studied extensively in large animals. The time to maximum concentration (Cmax) in large animals ranges from 1.2 to 4 days. Assuming an absorption half-life in humans of approximately one day (extrapolated from animal data) and a relatively short elimination half-life of 12-56 hours, steady state should be reached within one week of multiple dosing. Subcutaneous administration produced significantly higher ivermectin levels (11.4-17.2 ng/mL) than oral administration in patients with disseminated strongyloidiasis.
Distribution: V_d: 3.1 to 3.5 L/kg (healthy males); high concentration in the liver and adipose tissue; does not readily cross the blood-brain barrier.
Protein binding: ~93% primarily to albumin.
Metabolism: Hepatic via CYP3A4 (major), CYP2D6 (minor), and CYP2E1 (minor).
Excretion: Feces; urine (<1%).

Tablet: Treatment of intestinal strongyloidiasis caused by Strongyloides stercoralis.
Solution for injection: Treatment of disseminated strongyloides infection (Strongyloidiasis) in patient who cannot take tablet dosage form.

Tablet: Strongyloidiasis of the intestinal tract.
Single dose: Approximately 200 mcg/kg. (See table.)

Click on icon to see table/diagram/image

The safety and efficacy of ivermectin in children weighing less than 15 kg have not been established.
Solution for injection: Strongyloidiasis: 200 mcg/kg of subcutaneous daily; perform follow-up stool examinations.
Mode of Administration: Tablet: Ivermectin is administered orally as tablets. The tablets should be taken on an empty stomach with water.
Solution for injection: Subcutaneous injection.

Overdose and treatment: Accidental intoxication with substantial or unknown quantities of veterinary formulations of ivermectin in humans by ingestion, inhalation, injection, or exposure to body surfaces has been most frequently associated with rash, edema, headache, dizziness, asthenia, nausea, vomiting, and diarrhea; seizure, ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis also have been reported.
If accidental poisoning with ivermectin occurs, supportive measures, including parenteral fluids and electrolytes, respiratory therapy (e.g., oxygen, mechanical ventilation), and pressor agents should be instituted if indicated. Emesis and/or gastric lavage should be induced as soon as possible. Additional measures (e.g., purgatives) may be indicated if needed to prevent absorption of ingested material.

Hypersensitivity to ivermectin or any component of the formulation.

Because ivermectin may interact with γ-aminobutyric acid (GABA) receptors in the CNS, the drug is not recommended in patients with an impaired blood-brain barrier (e.g., meningitis, African trypanosomiasis) or CNS disorders that may increase penetration of the drug into the CNS.
Pharmacogenomic Neurotoxicity Considerations: In humans, P-glycoprotein, encoded by the multi-drug resistance gene (MDR1), functions as a drug efflux transporter and appears to limit the uptake of ivermectin into the brain, thereby preventing potentially fatal neurotoxicity in most humans. However, neurotoxicity manifested as tremors, ataxia, sweating, lethargy, coma, and death has occurred in certain animals (e.g., collie dogs, inbred strains of mice) who exhibit an extreme sensitivity to ivermectin; this increased sensitivity to the drug's neurologic effects appears to be secondary to absent or dysfunctional MDR and P-glycoprotein. It is theoretically possible that some individuals could experience increased brain concentrations of ivermectin or increased sensitivity to the drug's effects leading to neurotoxicity because of altered expression or function of P-glycoprotein (e.g. through genetic polymorphism, concomitant use of inhibitors of the P-glycoprotein transport system) or other mechanisms, although extensive use of ivermectin in mass treatment programs indicates that such an increased susceptibility, if it exists, must occur rarely in humans. Although a number of single-nucleotide polymorphisms in MDR1 have been identified in humans and the presence of genetic defects similar to those seen in susceptible animals cannot be ruled out, no cases with complete loss of P-glycoprotein activity have been reported in humans to date.
Solution for injection: The significance of ivermectin related to neurotoxicity in humans is still uncertain but given the findings in animal studies and reported human cases, this effect should be considered before use of parenteral ivermectin in humans.
Precautions in Strongyloidiasis: Individuals receiving ivermectin for the treatment of strongyloidiasis should be advised of the need for repeated stool examinations to document clearance of Strongyloides stercoralis infection. In immunocompromised (e.g., HIV-infected) patients receiving ivermectin for the treatment of intestinal strongyloidiasis, an optimal dosage regimen has not been established through adequate and well-controlled clinical studies. Several courses of therapy (i.e., at intervals of 2 weeks) may be necessary and cure may not be achieved. Control of extra-intestinal strongyloidiasis in such patients is difficult, and suppressive treatment (i.e., once monthly) may be helpful.
Use in Children: The safety and efficacy of ivermectin in children weighing less than 15 kg have not been established. Some clinicians state that use of ivermectin is not recommended in young children (e.g., those weighing less than 15 kg or younger than 2 years of age) in part because the blood-brain barrier may be less developed than in older patients.
Use in the Elderly: Clinical studies of ivermectin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. While other clinical experience has not revealed age-related differences in response to ivermectin, the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly should be considered.

Pregnancy: Category C.
Adverse events have been observed in animal reproduction studies. There are no adequate and controlled studies to date in humans, ivermectin should not be used during pregnancy since safety in pregnancy has not been established.
Lactation: Ivermectin is distributed into milk in low concentrations. Ivermectin should be used in nursing women only when the risk of delayed treatment to the woman outweighs the possible risk to the nursing infant.

Cardiovascular: Facial edema, orthostatic hypotension, peripheral edema, tachycardia.
Central nervous system: Dizziness.
Dermatologic: Dermatological reaction (includes edema, urticarial rash), pruritus.
Gastrointestinal: Diarrhea, nausea.
Hematologic & oncologic: Decreased white blood cell count, eosinophilia, increased hemoglobin.
Hepatic: Increased serum ALT, increased serum AST.
Rare but important or life-threatening: Abdominal distension, abdominal pain, abnormal gait, abnormal sensation in eyes, anemia, anorexia, anterior uveitis, ataxia, back pain, chest discomfort, chorioretinitis, coma, confusion, conjunctivitis, constipation, drowsiness, dyspnea, exacerbation of asthma, eye redness, eyelid edema, fatigue, fecal incontinence, headache, hepatitis, hypotension, increased serum bilirubin, keratitis, lethargy, leukopenia, mental status changes, myalgia, neck pain, posterior uveitis, seizure, skin rash, Stevens-Johnson syndrome, stupor, temporary vision loss, toxic epidermal necrolysis, tremor, urinary incontinence, urticaria, vertigo, vomiting, weakness.

Ivermectin is principally metabolized by the cytochrome P450 (CYP) isoenzyme 3A4 and, to a lesser extent, CYP2D6 and 2E1. Ivermectin does not inhibit CYP isoenzymes 3A4, 2D6, 2C9, 1A2, and 2E1.
Drugs with γ-Aminobutyric acid (GABA)-Potentiating Activity: Concurrent therapy with ivermectin and drugs with GABA-potentiating activity (e.g., barbiturates, benzodiazepines, sodium oxybate, valproic acid) is not recommended.
Benzodiazepines: Ivermectin may potentiate the activity of benzodiazepines. Concurrent therapy with ivermectin and benzodiazepines is not recommended.
Drugs Affecting or Affected by P-glycoprotein Transport: Ivermectin appears to be a substrate of the P-glycoprotein transport system; thus, interactions with inhibitors (e.g., amiodarone, carvedilol, clarithromycin, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidine, ritonavir, tamoxifen, verapamil) or inducers (e.g., amprenavir, clotrimazole, phenothiazines, rifampin, ritonavir, St. John's wort) of the P-glycoprotein transporter are theoretically possible.
Anticoagulants: There have been postmarketing reports of elevated international normalized ratio (INR) when ivermectin was used concomitantly with warfarin.

Tablet: Store below 30°C.
Solution for injection: Store below 30°C and protect from light.

Anthelmintics

P02CF01 - ivermectin ; Belongs to the class of avermectine agents. Used as antinematodal.

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