Merck warns on Ivermectin for COVID: No evidence of efficacy and safety

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Drug maker Merck & Co has warned against the use of Ivermectin to treat COVID-19, saying there is no evidence of its efficacy and safety. The anti-parasite drug has been around for more than 40 years.

The South African Health Products Regulatory Authority (SAHPRA) also warned this week that Ivermectin is still illegal in South Africa for use in the treatment and prevention of COVID-19 in humans, except by approved medical practitioners in controlled compassionate use.

The full Merck statement reads:

Merck today affirmed its position regarding use of ivermectin during the COVID-19 pandemic. Company scientists continue to carefully examine the findings of all available and emerging studies of ivermectin for the treatment of COVID-19 for evidence of efficacy and safety. It is important to note that, to-date, our analysis has identified:

No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;

No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;

A concerning lack of safety data in the majority of studies.

We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.

Indications and Usage for STROMECTOL (ivermectin)

Ivermectin is approved in the United States under the brand name STROMECTOL. STROMECTOL is indicated for the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis and for the treatment of onchocerciasis due to the nematode parasite Onchocerca volvulus.

STROMECTOL has no activity against adult Onchocerca volvulus parasites.

SELECTED SAFETY INFORMATION FOR STROMECTOL (ivermectin)

Contraindications

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

Warnings and Precautions

Patients treated with STROMECTOL for onchocerciasis may experience cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions.

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. 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.

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.

Adverse Reactions

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%).

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%).

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%.

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 ³1% 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).

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.

Drug Interactions

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

Use in Specific Populations

Ivermectin should not be used during pregnancy since safety in pregnancy has not been established.

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.

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.

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.


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