Stromectol

Ivermectin is usually taken as a single dose. Tell your doctor if you do not take your medication.

Pharmacokinetics

Following oral administration of ivermectin, plasma concentrations are approximately proportional to the dose. In two studies, after single 12-mg doses of STROMECTOL (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 2.5fold 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.

Microbiology

Ivermectin is a member of the avermectin class of broad-spectrum antiparasitic agents which have a unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This 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. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).

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.

Ivermectin is active against various life-cycle stages of many but not all nematodes. It is active against the tissue microfilariae of Onchocerca volvulus but not against the adult form. Its activity against Strongyloides stercoralis is limited to the intestinal stages.

Clinical Studies

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 STROMECTOL (ivermectin) (a single dose of 170 to 200 mcg/kg) than for albendazole (200 mg b.i.d. for 3 days). STROMECTOL (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.

Summary of Cure Rates for Ivermectin Versus Comparative Agents in the Treatment of Strongyloidiasis

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 STROMECTOL (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 STROMECTOL (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 STROMECTOL (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.

Ivermectin lotion is a no-comb,10-minute prescription treatment used to treat head lice infestations in adults and children 6 months of age and older.

Ivermectin is also available in tablet form. It is a prescription medication used to treat two types of roundworm parasites. It is usually taken as a single dose on an empty stomach with water.

Ivermectin is also available in a topical cream that is used to treat rosacea.

Ivermectin belongs to a group of drugs called antihelmintics. It works by killing the target parasite.

Common side effects of ivermectin lotion include eye redness and irritation, dandruff, and dry skin.

Common side effects of ivermectin tablets include loss of appetite, nausea, vomiting, and dizziness. Do not drive or operate heavy machinery until you know how this medication affects you.

Stromectol is part of the drug class:

• Avermectines

Oral:

Before taking ivermectin,

• tell your doctor and pharmacist if you are allergic to ivermectin or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you have or have ever had meningitis, human African trypanosomiasis (African sleeping sickness; an infection that is spread by the bite of the tsetse fly in certain African countries), or conditions that affect your immune system, such as human immunodeficiency virus (HIV).
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant during your treatment with ivermectin, call your doctor.
• ask your doctor about the safe use of alcoholic beverages while you are taking ivermectin.
• if you have had loiasis (Loa loa infection with a type of worm that causes skin and eye problems) or if you have ever lived in or traveled to areas of West or Central Africa where loiasis is common.

Topical:

Before using ivermectin lotion, tell your healthcare provider if you or your child:

• have any skin conditions or sensitivities
• have any other medical conditions
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed
• are taking any prescription and/or nonprescription medications, vitamins, nutritional supplements, and herbal products

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Oral:

For the treatment of strongyloidiasis (threadworm):

For the treatment of onchocerciasis (river blindness):

Topical:

• Apply ivermectin lotion to dry hair in an amount sufficient (up to 1 tube) to thoroughly coat the hair and scalp.

Other drugs may interact with ivermectin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Appears to be metabolized principally by CYP3A41 41 and, to lesser extent, by 2D6 and 2E1.1 Does not inhibit CYP3A4, 2D6, 2C9, 1A2, and 2E1.1

Drugs with GABA-potentiating Activity

Concomitant use with drugs with GABA-potentiating activity (e.g., barbiturates, benzodiazepines, sodium oxybate, valproic acid) not recommended.13 80 Ivermectin may interact with GABA receptors in the CNS.2 4 13 91

Drugs Affecting or Affected by P-glycoprotein Transport

Appears to be a substrate of P-glycoprotein transport system.13 40 48 80 Theoretical possibility of interactions with inducers (e.g., amprenavir, clotrimazole, phenothiazines, rifampin, ritonavir, St. John’s wort) or inhibitors (e.g., amiodarone, carvedilol, clarithromycin, cyclosporine, erythromycin, itraconazole, ketoconazole, quinidine, ritonavir, tamoxifen, verapamil) of this system.13 40 48 80 Concomitant use with inhibitors theoretically could result in increased brain concentrations of ivermectin and neurotoxicity5 48

Specific Drugs

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations attained in about 4 hours.1 6 14 35

Food

High-fat meal may increase absorption, but effect of food on bioavailability not evaluated using usual dosage (150–200 mcg/kg).1 33

Distribution

Extent

Concentrated in liver and adipose tissue.42

Does not readily cross blood-brain barrier.1 5 48 91 Brain uptake apparently limited by P-glycoprotein transport system.5 13 48 91 92 (See Neurotoxicity under Cautions.)

Distributed into milk in low concentrations.1

Plasma Protein Binding

Approximately 93%;75 principally albumin and, to a lesser extent, α 1-acid glycoprotein.34

Elimination

Metabolism

Metabolized in the liver,1 principally by CYP3A4.1 41

Appears to be a substrate of the P-glycoprotein transport system.40 48 49

Elimination Route

Excreted almost exclusively in feces (within approximately 12 days); <1% excreted in urine.1 14 33 35

Half-life

Approximately 18 hours following oral administration.1 33

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Eye or eyelid irritation, pain, redness, or swelling

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Fever, itching or skin rash
• joint or muscle pain
• painful and tender glands in neck, armpits, or groin
• rapid heartbeat

• Headache
• swelling of the face, hands, arms, feet, or legs

• Diarrhea
• dizziness
• skin rash or itching

• Lightheadedness when getting up from a lying or sitting position

• Loss of appetite
• shaking or trembling
• sleepiness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Applies to ivermectin: oral tablet

Along with its needed effects, ivermectin (the active ingredient contained in Stromectol) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking ivermectin:

• Eye or eyelid irritation, pain, redness, or swelling

Some side effects of ivermectin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Fever, itching or skin rash
• joint or muscle pain
• painful and tender glands in neck, armpits, or groin
• rapid heartbeat

• Headache
• swelling of the face, hands, arms, feet, or legs

• Diarrhea
• dizziness
• skin rash or itching

• Lightheadedness when getting up from a lying or sitting position

• Loss of appetite
• shaking or trembling
• sleepiness

Applies to ivermectin: compounding powder, oral tablet

General

Ivermectin (the active ingredient contained in Stromectol) is well tolerated compared to other microfilaricidal agents (i.e., thiabendazole, diethylcarbamazine). Adverse reactions (i.e., pruritus, fever, rash, myalgia, headache) occur commonly during the first 3 days after treatment and appear to be related to the extent of parasitic infection and systemic mobilization and killing of microfilariae. The majority of reactions can usually be treated with aspirin, acetaminophen and/or antihistamines. Adverse effects tend to occur with lesser frequency during periods of retreatment.[Ref]

Ocular

Ocular side effects have included eyelid edema, anterior uveitis, blurred vision, conjunctivitis, limbitis, punctate opacity, keratitis, abnormal sensation in the eyes, and chorioretinitis/choroiditis; however, these effects are also associated with the disease onchocerciasis. Loss of vision has occurred rarely but usually resolved without corticosteroid treatment. Conjunctival hemorrhage has been reported during postmarketing experience in patients treated for onchocerciasis.[Ref]

Other

Worsening of Mazzotti reactions, including arthralgia, synovitis, lymph node enlargement and tenderness, pruritus, skin involvement (including edema, papular and pustular or frank urticarial rash), and fever, has been reported during the first 4 days following treatment for onchocerciasis.

Nervous system

Nervous system side effects have included dizziness, headache, somnolence, vertigo, and tremor. Serious or fatal encephalopathy has been reported rarely in patients with onchocerciases, and heavily infected with Loa loa, either spontaneously or after treatment with ivermectin (the active ingredient contained in Stromectol) Seizures have been reported during postmarketing experience.[Ref]

Gastrointestinal

Gastrointestinal side effects have included anorexia, constipation, diarrhea, nausea, vomiting, and abdominal distention.[Ref]

Other

Other side effects have included asthenia, fatigue, abdominal pain, chest discomfort, facial edema, and peripheral edema.

Hematologic

Hematologic side effects have included decreased leukocyte count (3%), eosinophilia (3%), and increased hemoglobin (1%). Hematomatous swellings associated with prolonged prothrombin times have been reported, but the clinical significance is unknown. Leukopenia and anemia have been reported in at least one patient.[Ref]

Hepatic

Hepatic side effects have included elevated ALT and/or AST. Elevated liver enzymes, elevated bilirubin, and hepatitis have been reported during postmarketing experience.[Ref]

Cardiovascular

Cardiovascular side effects have included tachycardia and orthostatic hypotension. EKG changes, including prolonged PR interval, flattened T waves and peaked T waves, have been reported in single cases. Hypotension (primarily orthostatic hypotension) has been reported during postmarketing experience.[Ref]

Dermatologic

Dermatologic side effects have included pruritus, rash, and urticaria. Toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported during postmarketing experience.

Respiratory

Respiratory side effects have included worsening bronchial asthma, laryngeal edema, and dyspnea.[Ref]

Musculoskeletal

Musculoskeletal side effects have included myalgia.

Renal

Renal side effects have included rare transient proteinuria.[Ref]

Some side effects of Stromectol may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.