Usage
Ivermectin is an antiparasitic drug primarily used to treat infections caused by certain parasitic worms. It is effective against several nematodes (roundworms) like Onchocerca volvulus (causing Onchocerciasis or River Blindness), Strongyloides stercoralis (causing Strongyloidiasis), and other intestinal worms. It is also used topically for ectoparasites like Sarcoptes scabiei (causing scabies) and head lice.
Pharmacological Classification: Antiparasitic, Anthelmintic
Mechanism of Action: Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. This binding increases the permeability of the cell membrane to chloride ions, leading to hyperpolarization of the cell and paralysis and death of the parasite.
Alternate Names
Ivermectin is the generic name.
Brand Names: Stromectol is a commonly known brand name. Other brand names may exist regionally.
How It Works
Pharmacodynamics: Ivermectin acts on glutamate-gated chloride ion channels specific to invertebrates, leading to paralysis and death of the parasite. It has limited effects on mammalian GABA-gated chloride channels due to their lower affinity for the drug.
Pharmacokinetics:
- Absorption: Ivermectin is rapidly absorbed after oral administration, reaching peak plasma concentrations in approximately 4 hours.
- Distribution: The drug is widely distributed throughout the body, reaching various tissues, including the liver, kidneys, and adipose tissue. It does not readily cross the blood-brain barrier in therapeutic doses, minimizing central nervous system side effects.
- Metabolism: Ivermectin is primarily metabolized in the liver by CYP3A4 enzymes, resulting in various inactive metabolites.
- Elimination: The drug and its metabolites are primarily excreted in the feces via biliary excretion, with a small portion eliminated in the urine. The elimination half-life is approximately 18 hours.
Mode of Action: Ivermectin targets glutamate-gated chloride channels in invertebrate nerve and muscle cells, enhancing chloride influx and leading to hyperpolarization, resulting in paralysis and death of the parasites.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: The primary mechanism involves binding to and modulating glutamate-gated chloride ion channels in invertebrates. It can also weakly interact with mammalian GABA receptors.
Dosage
Standard Dosage
Adults:
- Onchocerciasis: 150 mcg/kg of body weight as a single oral dose, repeated every 6 to 12 months as needed.
- Strongyloidiasis: 200 mcg/kg of body weight as a single oral dose. Repeat dosing may be necessary in immunocompromised individuals.
- Scabies: 200 mcg/kg of body weight as a single oral dose, may repeat after one week if necessary.
Children:
- Onchocerciasis & Strongyloidiasis: Same as adult dosing (mcg/kg) for children weighing 15 kg or more. Ivermectin is not recommended for children weighing less than 15 kg. Pediatric safety in this weight group has not been established.
Special Cases:
- Elderly Patients: No specific dosage adjustments are generally recommended unless significant hepatic or renal impairment is present. Close monitoring for adverse effects is advised.
- Patients with Renal Impairment: No specific dosage adjustments are typically necessary as the drug is primarily eliminated via biliary excretion.
- Patients with Hepatic Dysfunction: Caution is advised in patients with severe hepatic impairment. Dosage adjustments may be needed.
- Patients with Comorbid Conditions: Considerations for comorbidities like diabetes, cardiovascular diseases, or HIV should be made on a patient-specific basis. Immunocompromised patients (e.g., HIV) may require higher doses or repeat treatment for strongyloidiasis.
Clinical Use Cases
Ivermectin is not typically used in settings like intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU), or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dosage adjustments may be needed in patients with severe liver disease. Consideration should also be given to immune status, as individuals with weakened immune systems may require longer courses or higher doses for certain infections.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Nausea
- Diarrhea
- Abdominal pain
- Loss of appetite
- Weakness
- Itching (especially with Onchocerciasis treatment as microfilariae die)
- Joint and muscle pain
- Rash
Rare but Serious Side Effects:
- Seizures
- Hypotension (low blood pressure)
- Hepatotoxicity (liver damage)
- Severe skin reactions (e.g., Stevens-Johnson syndrome)
- Ocular toxicity (eye inflammation, vision changes)
- Mazzotti reaction (worsening of Onchocerciasis symptoms due to the dying microfilariae, including fever, lymph node swelling, joint pain, itching)
- Encephalopathy (brain inflammation), particularly in patients co-infected with Loa loa.
Long-Term Effects:
No significant long-term effects have been identified with the typical short-term use of Ivermectin.
Adverse Drug Reactions (ADR):
Serious ADRs such as severe allergic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, and encephalopathy require immediate medical attention.
Contraindications
- Hypersensitivity to ivermectin.
- Pregnancy (unless the benefits outweigh the risks)
- Children weighing less than 15 kg (for oral formulations)
- Patients with pre-existing CNS conditions (caution advised)
- Patients co-infected with Loa loa (increased risk of severe encephalopathy).
Drug Interactions
- Warfarin: Ivermectin may potentiate the anticoagulant effect of warfarin. Monitor INR closely.
- CYP3A4 Inhibitors/Inducers: Drugs that inhibit or induce CYP3A4 enzymes may alter ivermectin metabolism.
- CNS Depressants: Concomitant use with other CNS depressants (e.g., benzodiazepines, barbiturates) may increase the risk of sedation.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (FDA). Animal studies have shown adverse effects, and while human data is limited, ivermectin is generally contraindicated during pregnancy unless the benefits clearly outweigh the risks.
- Breastfeeding: Ivermectin is excreted in breast milk. While serious adverse effects in infants have not been reported, breastfeeding should be avoided if possible during ivermectin treatment.
Drug Profile Summary
- Mechanism of Action: Binds to glutamate-gated chloride ion channels in invertebrates, causing paralysis and death.
- Side Effects: Dizziness, headache, nausea, diarrhea, itching, rash. Serious but rare: seizures, hypotension, hepatotoxicity, ocular toxicity, encephalopathy.
- Contraindications: Hypersensitivity, pregnancy, children <15 kg, Loa loa co-infection.
- Drug Interactions: Warfarin, CYP3A4 inhibitors/inducers, CNS depressants.
- Pregnancy & Breastfeeding: Generally contraindicated in pregnancy. Avoid breastfeeding during treatment.
- Dosage: Onchocerciasis: 150 mcg/kg; Strongyloidiasis/Scabies: 200 mcg/kg orally, repeated as needed.
- Monitoring Parameters: Liver function tests (especially with prolonged use), neurological status (especially in patients at risk of encephalopathy), INR if co-administered with warfarin.
Popular Combinations
Ivermectin is not commonly used in combination with other drugs for its indicated parasitic infections, as single-dose therapy is often sufficient. However, in mass drug administration campaigns for lymphatic filariasis, it may be used in combination with albendazole to broaden the antiparasitic spectrum.
Precautions
- Assess for allergies and any contraindications before administration.
- Screen for potential Loa loa co-infection in individuals from West and Central Africa.
- Monitor for liver function, especially with prolonged use.
- Advise patients about potential side effects, including Mazzotti reactions (in Onchocerciasis).
- Ensure accurate weight-based dosing, especially in children.
- Caution patients about potential dizziness and advise against driving or operating machinery until the effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ivermectin?
A: The dosage depends on the infection being treated. For Onchocerciasis, it’s 150 mcg/kg as a single oral dose, repeated every 6-12 months. For Strongyloidiasis and Scabies, it’s 200 mcg/kg as a single oral dose, possibly repeated as needed.
Q2: Can Ivermectin be used in pregnant women?
A: Ivermectin is generally contraindicated during pregnancy due to potential fetal risks. It should only be used if the potential benefits clearly outweigh the risks.
Q3: What are the common side effects of Ivermectin?
A: Common side effects include dizziness, headache, nausea, diarrhea, abdominal pain, weakness, itching, and rash.
Q4: Are there any serious side effects to be aware of?
A: Rarely, serious side effects like seizures, low blood pressure, liver damage, severe skin reactions, eye problems, and encephalopathy can occur.
Q5: How does Ivermectin interact with Warfarin?
A: Ivermectin may enhance the anticoagulant effect of warfarin. Close monitoring of INR is necessary if these drugs are used together.
Q6: Can Ivermectin be used in children?
A: Oral Ivermectin can be used in children weighing 15 kg or more, with weight-based dosing similar to adults. It is not recommended for children weighing less than 15 kg.
Q7: What precautions should be taken in patients from West and Central Africa?
A: Patients from these regions should be screened for Loa loa co-infection, as Ivermectin can cause severe encephalopathy in co-infected individuals.
A: Ivermectin is primarily metabolized in the liver by CYP3A4 enzymes.
Q9: What is the primary route of elimination for Ivermectin?
A: Ivermectin and its metabolites are primarily excreted in the feces via biliary excretion.
Q10: Should Ivermectin be taken with food?
A: Ivermectin should be taken on an empty stomach with water, at least 1 hour before a meal, as food can increase its absorption.
