STROMECTOL Tablet Ref.[27591] Active ingredients: Ivermectin

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 STROMECTOL for onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, probably, or definitely related to the drug itself. (See ADVERSE REACTIONS, Onchocerciasis.)

The treatment of severe Mazzotti reactions has not been subjected to controlled clinical trials. Oral hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to treat postural hypotension. Antihistamines and/or aspirin have been used for most mild to moderate cases.

Strongyloidiasis

In four clinical studies involving a total of 109 patients given either one or two doses of 170 to 200 mcg/kg of STROMECTOL, the following adverse reactions were reported as possibly, probably, or definitely related to STROMECTOL:

Body as a Whole: asthenia/fatigue (0.9%), abdominal pain (0.9%)

Gastrointestinal: anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%), vomiting (0.9%)

Nervous System/Psychiatric: dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor (0.9%)

Skin: pruritus (2.8%), rash (0.9%), and urticaria (0.9%).

In comparative trials, patients treated with STROMECTOL experienced more abdominal distention and chest discomfort than patients treated with albendazole. However, STROMECTOL was better tolerated than thiabendazole in comparative studies involving 37 patients treated with thiabendazole.

The Mazzotti-type and ophthalmologic reactions associated with the treatment of onchocerciasis or the disease itself would not be expected to occur in strongyloidiasis patients treated with STROMECTOL. (See ADVERSE REACTIONS, Onchocerciasis.)

Laboratory Test Findings

In clinical trials involving 109 patients given either one or two doses of 170 to 200 mcg/kg STROMECTOL, 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 involving 963 adult patients treated with 100 to 200 mcg/kg STROMECTOL, worsening of the following Mazzotti reactions during the first 4 days post-treatment were reported: arthralgia/synovitis (9.3%), axillary lymph node enlargement and tenderness (11.0% and 4.4%, respectively), cervical lymph node enlargement and tenderness (5.3% and 1.2%, respectively), inguinal lymph node enlargement and tenderness (12.6% and 13.9%, respectively), other lymph node enlargement and tenderness (3.0% and 1.9%, respectively), pruritus (27.5%), skin involvement including edema, papular and pustular or frank urticarial rash (22.7%), and fever (22.6%). (See WARNINGS.)

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 STROMECTOL. 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%. (See WARNINGS.)

In clinical trials involving 963 adult patients who received 100 to 200 mcg/kg STROMECTOL, 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.

The following ophthalmological side effects do occur due to the disease itself but have also been reported after treatment with STROMECTOL: abnormal sensation in the eyes, eyelid edema, anterior uveitis, conjunctivitis, limbitis, keratitis, and chorioretinitis or choroiditis. These have rarely been severe or associated with loss of vision and have generally resolved without corticosteroid treatment.

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%).

Post-Marketing Experience

The following adverse reactions have been reported since the drug was registered overseas:

Onchocerciasis

Conjunctival hemorrhage

All Indications

Hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal necrolysis, Stevens-Johnson syndrome, seizures, hepatitis, elevation of liver enzymes, and elevation of bilirubin.

Strongyloidiasis in Immunocompromised Hosts

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.

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.

Rarely, patients with onchocerciasis who are also heavily infected with Loa loa may develop a serious or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide. In these patients, the following adverse experiences have also been reported: pain (including neck and back pain), red eye, conjunctival hemorrhage, dyspnea, urinary and/or fecal incontinence, difficulty in standing/walking, mental status changes, confusion, lethargy, stupor, seizures, or coma. This syndrome has been seen very rarely following the use of ivermectin. In individuals who warrant treatment with ivermectin for any reason and have had significant exposure to Loa loa-endemic areas of West or Central Africa, pretreatment assessment for loiasis and careful post-treatment follow-up should be implemented.

STROMECTOL should be taken on an empty stomach with water. (See CLINICAL PHARMACOLOGY, Pharmacokinetics.)

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 STROMECTOL does not kill the adult Onchocerca parasites, and therefore repeated follow-up and retreatment is usually required.

Post-marketing reports of increased INR (International Normalized Ratio) have been rarely reported when ivermectin was co-administered with warfarin.

Teratogenic Effects

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.

STROMECTOL 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.

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

Clinical studies of STROMECTOL 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.