Azithromycin/chloroquine

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case series, three patients aged 11−16 years [including two males; not all sexes stated] were described, who developed seizure, generalised tonic clonic seizure, clonic seizures or focal epilepsy during off label treatment with chloroquine for COVID-19 infection [routes not stated; not all duration of treatments to reaction onsets stated].

Case 1: A 14-year-old boy was admitted to the emergency room for loss of consciousness, recurrent tonic-clonic seizures and post critical confusion for 4 hours before admission. He was epileptic since the age of 9 years, and was receiving sodium valproate regularly for epileptic seizure. Prior to the admission, he had developed flu-like syndrome, which was treated unsuccessfully with paracetamol [acetaminophen] and ascorbic acid. At current presentation, he was transferred to the ICU. While in hospital, he presented with recurrent paroxysmal seizures within a short period of time, without return to normal consciousness between seizures. A diagnosis of status with septic shock was made. The status epilepticus was treated with clonazepam, phenobarbital and thiopental sodium [thiopental]. The intercritical EEG tracing suggested multifocal epilepsy. The COVID-19 PCR confirmatory test was positive. Subsequently, he was started on off label chloroquine 500 mg/day [chloroquine sulfate]. Chloroquine was discontinued as recommended by the neurologist due to the paroxysmal recurrence of seizures. Afterwards, he received corticosteroid therapy and rest of the management was symptomatic. After one month without seizures, he was discharged.

Case 2: An 11-year-old patient was confirmed positive for COVID-19 infection and started receiving off-label treatment with chloroquine 500 mg/day [chloroquine sulfate] and azithromycin 250 mg/day. After one week of treatment, the patient experienced loss of consciousness with generalized tonic-clonic seizure. The patient also developed lateral biting of the tongue, hyper salivation and loss of urine. Clinical examination was notable for respiratory difficulty and tachycardia. Neurological examination showed persistent mental confusion for more than one hour. Other biological parameters reveal a non-specific inflammatory syndrome. An electrocardiogram (ECG) revealed a heart rhythm disorder. Chloroquine was stopped and clonazepam was initiated. Benzodiazepam [unspecified] was also added. Background antiepileptic levitracetam [Keppra] was added following the second seizure. The patient recovered from COVID-19 infection. After absence of seizure for 3 weeks, a brain scan and EEG were found normal. The patient was discharged with recommendation of neurological surveillance.

Case 3: A 16-year-old boy was diagnosed with COVID-19 and started receiving off label treatment with chloroquine 500 mg/day [chloroquine sulfate] and azithromycin 250 mg/day. After 4 days of treatment, he experienced a loss of consciousness with Bravais Jacksonian clonic seizures of the right hemicorps. Rest of the neurological examination was normal. He was diagnosed with focal epilepsy with roladic paroxysm. Other biological parameters revealed a non-specific inflammatory syndrome. Chloroquine treatment was discontinued and he was initiated on clonazepam and unspecified benzodiazepine. After a repeat attack within 48 hours of discontinuation of chloroquine, levitracetam was started. Within 16 days of seizure-free follow-up and two negative RT-PCR tests, he was discharged. After recovery, a brain CT scan and EEG showed no abnormalities.