Table 1.

Case series describing serious neurological adverse events after treatment with ivermectin beyond the onchocerciasis indication

Case	Age/sex	Indication	Dose	Weight (kg)	Other suspect (S) or concomitant (C) medications	Reported adverse event terms	Time to onset	Additional info
1	11/F	Scabies	9 mg	40	–	Encephalopathy, coma, emesis	1 day	Recovered. Positive dechallenge. Presented with depressed level of consciousness, without evidence of fever or hypoglycaemia. Glasgow coma scale 9. Naloxone given without effect. LP, EEG, and MRI all performed and negative. Multiple cultures and serologies negative.
2	28/M	Scabies	18 mg	–	–	Confusional state, amnesia, malaise, emesis	1 day	Recovered. Similar symptoms reported twice in the past after ivermectin. Presented with confusional state, Glasgow coma scale 13. Neurological exam negative.
3†	24/M	Scabies	3 mg	–	Oxatomide (S)	Confusion, convulsive disorder cephalgia, fatigue, fall	0 day	Recovered. Patient presented with headache, fatigue and fall. Sent to hospital. Sleepy but awake, opened eyes to pain. No evidence of tongue biting, urinary incontinence. Normal neurological exam, normal CT. No previous history of neurological disease.
4	18/M	Scabies infestation	15 mg	79	–	Lightheadedness, headache, unable to walk	1 day	“Patient developed headache and dizziness to the point of being unable to walk.” Positive dechallenge Recovered in 24 hours.
5	32/F	Scabies	24 mg	109	–	Tremor, dizzy spells, mucosal dryness, abdominal pain lower	8 hours	–
6	14/M	Scabies	1 DF*, 1 per 1 day	–	Piperonyl butoxide/esdepallethrime (topical) (S)	Dizziness, crying abnormal, monoparesis, tremor, rigors, chills	10 hours	Recovered. Positive dechallenge
7	48/F	Scabies	9 mg day 0, 9 mg day 7	68	Piperonyl butoxide/esdepallethrime (topical) (S)	Muscle weakness, hypoaesthesia, paraesthesia	–	Recovered. Symptoms occurred after each dose of ivermectin and topical piperonyl butoxide. Lasted 20–40 minutes. Was unable to speak.
8	33/M	Scabies	12 mg	65	Darunavir, ritonavir (both S)	Convulsions generalized	1 day	Recovered. Positive dechallenge with all 3 drugs. Patient had started darunavir 12 months prior and ritonavir 8 days prior. Head scan normal.
9†	–/M	Scabies infestation	12 mg	70	Ranitidine, amantidine, trazadone, lorazepam, haloperidol, toprimate, hydroxyzine, risperidone (all C)	Confusional state, unconsciousness	–	–
10	81/M	Scabies	3 mg	–	–	Cerebellar syndrome, mental confusion, MRI abnormal	1–2 days	Drug withdrawn, no effect observed. Patient with altered state of consciousness, aggression, confusion. Exam revealed thrombocytopenia, eosinophilia, dehydration and renal failure. MRI abnormal 2 weeks after dosing.
11†	58/F	Acarodermatitis	12 mg	60	Alprazolam, Etizolam (both C)	Consciousness disturbed	0 day	Positive dechallenge. Recovered within 8 days. No dates of use for alprazolam or etizolam provided.
12†	51/M	Acarodermatitis	18 mg day 0, 18 mg day 7	79	Pregabalin, lamotrigine, aripiprazole, meloxicam, simvastatin, docusate (all C)	Abasia, aphasia, blindness, disease recurrence	–	Positive rechallenge
13	54/F	Acarodermatitis	Two “pills” day 0, two “pills” day 7	68	–	Convulsion, local swelling, nausea, headache, heart rate increased, confusional state	–	–
14	81/M	Acarodermatitis	9 mg	50	Rivastigmine, memantine, lornoxicam, troxipide (all C)	Tremor, pyrexia	0 day	Positive dechallenge
15†	–/–	Acarodermatitis	–	–	Valproic acid, levetiracetam (both C)	Seizure, off label use	–	No dates of use provided for any of the reported medicines. Only ivermectin reported as “suspected.”
16	81/F	Acarodermatitis	12 mg day 0, 12 mg day 7	–	Digoxin, rebamipide, crotamiton, magnesium oxide, senna (all C)	Depressed level of consciousness, vomiting, asphyxia, pruritus aggravated, skin eruption	5 days after last dose	Died, 5 days after last dose from the events of depressed level of consciousness and asphyxia. Digoxin initiated 1 day prior to death.
17†	56/F	Acarodermatitis	12 mg	55	Terbinafine (S), dexlansoprazole, milnacipran, gabapentin, promethazine, meloxicam, trazadone, levothyroxine, propranolol, Lisinopril, predinose, azathioprine, diazepam, nortriptyline, lansoprazole, amoxicillin, furosemide, hydrochloroquine, vitamin D, vitamins (all C)	Aphasia, somatic delusion abnormal faeces, alopecia, dry mouth, dyspnoea, ear infection, flushing, gastrointestinal motility disorder, headache, heart rate increased, lip swelling, musculoskeletal discomfort, oral discomfort, red blood cell count decreased, swollen tongue, urine color abnormal, urine odor abnormal, weight decreased white blood cell count decreased	2–5 days for aphasia and somatic delusion	Drug withdrawn, no effect observed
18	97/F	Acarodermatitis	9 mg day 0, 9 mg day 7	47	Febuxostat, furosemide, lansoprazole, sennoside a + b, magnesium oxide, carbocisteine, etizolam (all C)	Depressed level of consciousness, loss of consciousness, vomiting	6 days after 1st dose and 5 days after 2nd dose	Recovered. Positive dechallenge
19	64/M	Strongyloidiasis	12 mg oral then subcutaneous	57	–	Coma, neurotoxicity	–	Drug withdrawn, fatal outcome. Tx initiated for Strongyloides stercoralis infection in patient on prednisone for giant cell arteritis. Patient was s/p aortic valve replacement. Ivermectin levels measured in brain tissue at autopsy (30 ng/g). None of the most common polymorphisms in mdr-1 present.
20†	59/F	Strongyloidiasis Nematodiasis	21 mg day 0, 21 mg day 1	100	Levothyroxine, olopatadine, vitamines, omega-3, melatonin, ascorbic acid, formoterol/budesonide doxycycline, potassium citrate, pioglitazone, probiotics, vitamin D, prasterone, progesterone, colesevelam, montelukast. desvenlafaxine (all C)	Pain in jaw, tremor chest pain, chills back pain, tachycardia, dyspnoea, loss of consciousness, pain in extremity, thinking abnormal, peripheral coldness, hypersomnia, dizziness, asthenia, feeling abnormal, palpitations, paraesthesia, fatigue, blood potassium decreased, dysgeusia, constipation, muscle twitching, sedation, vertigo, sensation of heaviness, feeling cold, mood altered, feeling drunk, oropharyngeal pain, coxsackie virus test positive, inappropriate schedule of drug administration, orthostatic hypotension, neuralgia,affect lability, hypertension, asthma, confusional state, cough, nystagmus, headache, pyrexia, somnolence	1–2 days	Drug withdrawn, no effect observed.
21	–/M	Strongyloidiasis	18 mg day 0, 18 mg day 1	86	–	Quality of life decreased, sleep disorder	–	–
22	28/M	Filariasis due to Wuchereria bancrofti	12 mg	–	Albendazole (S), diclofenac, amoxicillin (both C)	Unconsciousness	0 day	Recovered. Gastric lavage. Patient concomitantly treated for Ascariasis
23	36/M	Filariasis due to Wuchereria bancrofti	12 mg	–	Albendazole (S)	Headache, vomiting, diarrhea, abdominal discomfort	1 day	Recovered Patient concomitantly treated for Ascariasis
24	43/F	Filariasis due to Wuchereria bancrofti	9 mg	–	Albendazole (S)	Headache, dizziness, vomiting	2 days	Recovered Patient concomitantly treated for Ascariasis
25	11/F	Filariasis due to Wuchereria bancrofti	9 mg	–	Albendazole (S)	Headache, Dizziness, Vomiting	0 day	Recovered Patient concomitantly treated for Ascariasis
26	72/M	Filariasis due to Wuchereria bancrofti	12mg	–	Albendazole (S)	Headache, abdominal discomfort, itching vomiting, oedema	0 day	Recovered Patient concomitantly treated for Ascariasis
27	–/F	Myiasis	12 mg	–	–	Seizure, off label use	–	Not recovered
28	75/F	Taeniasis	6 mg	59	Lisinopril, amlodipine, metoprolol, clopidogrel (all C)	Asthenia, dizziness, dyspnoea, paraesthesia, vision decreased	0 day	Recovered with sequelae

EEG = electroencephalogram; LP = lumbar puncture; MRI = magnetic resonance imaging.

^*DF = dosage form; for ivermectin, 1 dosage form = 3 g.

^†Cases with concomitant medications with central nervous system effects.