Evidence review: safety

Adverse events in studies of ivermectin

Adverse events reported in people receiving oral ivermectin in randomised controlled trials (RCTs) for classical or uncomplicated scabies include aggravation of symptoms (including pruritus), irritation, headache, nausea, pustular rash, cellulitis, abdominal pain and mild diarrhoea.

Three trials reported no adverse events with either ivermectin or the comparator treatment (Macotela-Ruíz and Peña-González 1993, Bachewar et al. 2009 and Saqib et al. 2012).

Glaziou et al. (1993) and Nnoruka and Agu (2001) reported no adverse events with ivermectin but adverse events with benzyl benzoate (pruritus in 5/21 people in Glaziou et al. 1993 and pruritus and irritation in 7/29 people in Nnoruka and Agu 2001). Brooks and Grace (2002) reported adverse events in 4/43 participants in the ivermectin group (pustular rash or cellulitis) and in 12/37 participants in the benzyl benzoate group (burning, stinging or dermatitis). Ly et al. (2009) reported adverse events in 7/65 participants in the ivermectin group (abdominal pain or mild diarrhoea) and in 30/116 participants in the benzyl benzoate groups (irritant dermatitis).

In Usha and Gopalakrishnan Nair (2000), 3/43 participants in the ivermectin group reported aggravation of symptoms compared with none of 45 participants who received permethrin. In Sharma and Singal (2011), 6/80 people reported adverse events with ivermectin (headache and nausea) compared with 5/40 people who were treated with permethrin (transient burning sensation or pruritus). In Chhaiya et al. (2012), 2/100 people reported adverse events with oral ivermectin (headache and an increase in pruritus) compared with 1/99 receiving permethrin (burning sensation). In Goldust et al. (2012), 3/121 people reported irritation with ivermectin compared with 6/121 receiving permethrin.

In studies that reported the use of ivermectin for crusted scabies, 3 studies reported either no side effects or that no adverse effects were observed (Huffam and Currie 1998, Larralde et al. 1999 and Alberici et al. 2000). Nofal (2009) reported that no major adverse effects occurred. One person complained of gastric upset and 2 people experienced a transient increase in pruritus. Paasch and Haustein (2000) reported that one-third of people experienced an increase in pruritus for 2 days and haematomas developed in 2 people with an increase in prothrombin time.

Other sources of safety information

The European summary of product characteristics for Stromectol 3 mg tablets (Merck Sharp & Dohme: personal communication December 2013) lists side effects observed when using ivermectin to treat other parasitic conditions, such as strongyloidiasis or microfilaraemia. These include transient hypereosinophilia, liver function abnormalities, haematuria, toxic epidermal necrolysis, Stevens–Johnson syndrome, encephalopathy and hypersensitivity reactions. However, some of these side effects, such as those related to microfilarial density, may be specific to these conditions. The summary of product characteristics states that when ivermectin is used to treat scabies, transient exacerbation of pruritus may occur at the beginning of treatment. It also states that safety in paediatric patients weighing less than 15 kg has not been established.

Barkwell and Shields (1997) reported an association with ivermectin and an increased risk of death among a group of elderly people with scabies in a long-term care facility in Canada. However, the authors of the Cochrane systematic review and various discussions in the literature have questioned the validity of this report. It is unclear whether the increased risk of death was caused by ivermectin, interactions with other scabicides (including lindane and permethrin) or other treatments such as psychoactive drugs. The authors of the Cochrane systematic review suggest that ivermectin has been used widely in the treatment of onchocerciasis (river blindness) and even with repeated doses serious adverse effects have been rare.

Between 1 July 1963 and 12 December 2011, 16 adverse drug reactions for ivermectin (in 6 adverse drug reaction reports and 4 fatal adverse drug reaction reports) were reported to the Medicines and Healthcare Products Regulatory Agency (MHRA). It is not known how many people took ivermectin, or for what indication. In addition, it is important to note that healthcare professionals are asked to report even if they only have a suspicion that the medicine may have caused the adverse drug reaction. The fact that a report has been submitted does not necessarily mean that the medicine has been proven to cause an adverse drug reaction.