Revision Year: 2018 Publisher: SUBSTIPHARM DEVELOPPEMENT, 24 rue Erlanger, 75016 Parijs, Frankrijk
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Efficacy and dosing regimen of ivermectin in immunocompromised patients being treated for intestinal strongyloidiasis have not been established by adequate clinical studies. There have been reported cases which show the persistence of infestation following a single dose of ivermectin, particularly in this type of patients.
Ivermectin is not a prophylactic therapy of infection with filariae or anguillulosis; there are no data available demonstrating the efficacy of ivermectin, either for killing or preventing the maturation of infective larvae in humans. Ivermectin has not been shown to have any activity against the adult worm of any species of filariae.
Ivermectin has not been shown to have any beneficial effect on tropical pulmonary eosinophilia syndrome, on lymphadenitis or lymphangitis observed in case of infection with filariae.
Following administration of ivermectin, the intensity and severity of adverse experiences are probably related to the pretreatment microfilarial density particularly in the blood. In patients co-infected with Loa loa, microfilarial density, particularly in the blood, is most often high which predisposes the treated patients to an increased risk in the occurrence of serious adverse experiences.
CNS adverse experiences (encephalopathies) have been rarely reported in patients treated with ivermectin and co-infected by a high number of microfilariae of Loa loa. Consequently, in Loa loa endemic areas, special measures should be taken before any treatment with ivermectin (see section 4.8).
Concomitant treatment with diethylcarbamazine citrate (DEC) and ivermectin in mass chemotherapy campaigns for filariasis caused by Wuchereria Bancrofti in Africa is not recommended. Co-infection with other microfilariae, such as Loa loa may result in high microfilaraemia in patients infected.
Systemic exposure to DEC in such patients may result in the occurrence of serious side effects related to the rapid and effective microfilaricidal effects of this drug.
Following administration of drugs with a rapid microfilaricidal action such as DEC in patients with onchocerciasis, cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction), and ophthalmological reactions have been reported.
These reactions are probably due to inflammatory responses to degradation products released following the death of microfilariae.
Patients treated with ivermectin for onchoceriasis may also experience these reactions when treated for the first time. After treatment with a microfilaricidal drug, patients with hyperreactive onchodermatitis or “Sowda” (observed particularly in Yemen) may be more likely than others to experience severe cutaneous adverse reactions (oedema and aggravation of onchodermatitis).
Safety in paediatric patients weighing less than 15 kg of body weight has not been established.
No interaction studies have been performed.
During mass treatment of onchocerciasis, data on a limited number (approximately 300) of pregnant women indicated no adverse effects such as congenital anomalies, spontaneous abortions, stillbirths and infant mortality which might be associated with ivermectin treatment during the first trimester of pregnancy. To date, no other epidemiological data are available.
Animal studies have shown reproductive toxicity (see section 5.3); however, the predictive value of these observations has not been established.
Ivermectin should only be used when strictly indicated.
Less than 2% of the administered dose of ivermectin appears in breast milk. Safety of use has not been established in newborn infants. Ivermectin may only be given to breastfeeding mothers if the expected benefit outweighs the potential risk to the infant.
Ivermectin had no adverse effects on the fertility in rats up to 3 times the maximum recommended human dose of 200 μg/kg (on a mg/m²/d basis).
The effect of IVERMECTIN SUBSTIPHARM on the ability to drive and use machines has not been studied. The possibility in some patients of side effects such as dizziness, somnolence, vertigo and tremor, which may affect the ability to drive or use machines, cannot be excluded (see section 4.8).
Transient hypereosinophilia, liver dysfunction including acute hepatitis, increased liver enzymes, hyperbilirubinemia and haematuria have been reported.
Very rarely, toxic epidermal necrolysis and Stevens-Johnson syndrome have also been reported.
Side effects are related to the parasite density and are mild and transient in the majority of cases, but their severity may be increased in patients infected with more than one parasite, particularly in the case of infestation with Loa loa.
Rarely, severe and potentially fatal cases of encephalopathy have been described following administration of ivermectin, particularly in patients also heavily infected with Loa loa. In these patients, the following adverse reactions have also been reported: back or neck pain, ocular hyperaemia, subconjunctival haemorrhage, dyspnoea, urinary and/or faecal incontinence, difficulty in standing/walking, mental status changes, confusion, lethargy, stupor or coma (see section 4.4).
In patients receiving ivermectin for the treatment of strongyloidiasis, the following adverse reactions have been reported: asthenia, abdominal pain, anorexia, constipation, diarrhoea, nausea, vomiting, dizziness, somnolence, vertigo, tremor, transient hypereosinophilia, leukopenia/anaemia and increase in ALAT/alkaline phosphatases. In the treatment of Wuchereria bancrofti filariasis, the intensity of undesirable effects does not seem to be dose-dependent but is related to the microfilarial density in blood. The following have been described: fever, headache, asthenia, feeling of weakness, myalgia, arthralgia, diffuse pain, digestive disorders such as anorexia, nausea, abdominal and epigastric pain, cough, feeling of respiratory discomfort, sore throat, orthostatic hypotension, chills, vertigo, profuse sweating, testicular pain or feeling of discomfort.
Following administration of ivermectin in patients infected with Onchocerca volvulus, the hypersensitivity reactions observed resulting from microfilarial death pertain to Mazzotti-type reactions: pruritus, urticarial rash, conjunctivitis, arthralgia, myalgia (including abdominal myalgia), fever, oedema, lymphadenitis, adenopathies, nausea, vomiting, diarrhoea, orthostatic hypotension, vertigo, tachycardia, asthenia, headache. Rarely, these symptoms have been severe. A few cases of asthma exacerbation have been described. In these patients, abnormal sensation in the eyes, eyelid oedema, anterior uveitis, conjunctivitis, limbitis, keratitis and chorioretinitis or choroiditis have also been described. These manifestations, which may be due to the disease itself, have also been described occasionally after treatment. They were rarely severe and generally resolved without corticosteroid treatment.
Onset of conjunctival haemorrhage has been reported in patients with onchocerciasis. Observations of adult Ascaris expulsion have been described following ingestion of ivermectin.
In patients with scabies, transient exacerbation of pruritus may be observed at the start of treatment.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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