Revision Year: 2020 Publisher: Galenicum Derma, S.L., Ctra. N-1, Km 36, 28750 San Agustin de Guadalix (Madrid), Spain
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 Ivergalen 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).
The adverse reactions are classified by System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Common: Elevated transaminases, leukopeniab, lymphadenopathyd
Not known: Anaemiab
Common: Abdominal painb,c, abdominal pain upper, diarrhoeab,d, nauseab,c,d, vomitingb,d, epigastric painc, faecal incontinencea
Not known: Anal incontinence, constipationb, oropharyngeal pain
Common: Anorexiab,c
Not known: Edema
Common: Dizzinessb, vertigob,c,d, tremorb
Rare: Encephalopathya
Not known: Gait disturbance, comaa, headachec,d
Common: Somnolenceb
Not known: Mental status changesa, confusiona, stupora
Common: Pruritusd, rashd, urticariad
Not known: Back paina, neck paina, myalgiac,d, arthralgiac,d, chillsc
Very rare: Toxic epidermal necrolysis
Very rare: Stevens-Johnson syndrome
Not known: Asthma
Not known: Hypereosinophiliab, liver disorder, hepatitis acute, hyperbilirubinemia, liver function test abnormal
Not known: Hematuria, testicular painc
Not known: Ocular hyperaemiaa, subconjunctival haemorragea, iridocyclitis, limbitisd , keratitisd, choroiditisd, anterior uveitisd, eyelid oedemad, abnormal sensation in eyed
Not known: Urinary incontinencea
Not known: Dysstasiaa, lethargya, astheniab,c,d, pyrexiac,d, hyperhidrosis, discomfort, diffuse painc, feelings of weaknessc, walking difficultya, chillsc
Not known: Coughc, respiratory discomfortc, exacerbation of asthmad, sore throatc, dyspnoeaa
Not known: Orthostatic hypotensionc,d
Not known: Conjunctivitisd, chorioretinitisd
Not known: Lymphadenitisd
Not known: Tachycardiad
Not known: Liver enzyme elevations (ALAT/ALP)b
Not known: Excess sweatingc
a Patients infected with Loa loa
b Patients with intestinal strongyloidiasis
c Patients with Wuchereria bancrofti filariasis
d Patients infected with Onchocerca volvulus
Patients infected with Loa loa: 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.
Patients with scabies: transient exacerbation of pruritus may be observed at the start of treatment. Patients infected with Ascaris: Observations of adult Ascaris expulsion have been described following ingestion of ivermectin.
Patients with onchocerciasis: Onset of conjunctival haemorrhage has been reported.
A similar safety profile was observed in pediatric patients ages 6 to 13. The safety and efficacy of ivermectin in children weighing less than 15 kg have not been established. The use of ivermectin is not recommended in young children (e.g., those weighing less than 15 kg or younger than 2 years of age) in part because the blood-brain barrier may be less developed than in older patients.
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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