Multiple drugs interaction

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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

• * Drug interaction

In a report of 4 patients, a 61-year-old man and a 68-year-old woman were described, of whom the man developed reduction in valproate level following concomitant administration of valproate with meropenem, and the woman developed QTc prolongation following concomitant administration of venlafaxine with off label medications comprising azithromycin, hydroxychloroquine and lopinavir/ritonavir [routes not stated; not all dosages and times to reactions onsets stated].

Case 1 (61-year-old man): The man had personality and delusional disorder, and he had been receiving valproate 1000 mg/24h, mirtazapine and olanzapine. He was referred for medication adjustment. He was diagnosed COVID-19 (corona virus) pneumonia, and was started on in-patient off label treatment with lopinavir/ritonavir 400 mg/100mg every 12h, azithromycin 250 mg/24h and hydroxychloroquine 400 mg/24h. His initial valproate level was within therapeutic range. Subsequently, metronidazole and meropenem were added due to bacteraemia. Post antibiotics initiation, his valproate level was noted to be markedly reduced, likely due to interaction with meropenem. The dose of valproate was not changed, as the duration of meropenem therapy was short (5 days). ). Upon completion of meropenem therapy, the valproate level normalised.

Case 2 (68-year-old woman): The woman had generalised anxiety disorder with depressive disorder, and she had been receiving venlafaxine 225 mg/24h for more than 5 years, and trazodone and vortioxetine were added 5 months ago in view of worsening of depressive symptoms. She was referred for medication adjustment. She was diagnosed with COVID-19 (corona virus) pneumonia and was admitted. On day 1 of admission, she started receiving off label treatment with azithromycin 250 mg/24h, hydroxychloroquine 400 mg/24 h and lopinavir/ritonavir 400 mg/100mg every 12h for COVID-19 (corona virus) pneumonia. Trazodone and vortioxetine were stopped, and only venlafaxine was continued at the same dosage. On day 2 of admission, she developed mild QTc prolongation (QTc - 443ms) requiring venlafaxine interruption. The occurrence of QTc prolongation was suspected to be due to interaction between venlafaxine, and azithromycin, hydroxychloroquine and lopinavir/ritonavir. Since the day of admission, she presented with worsening of anxiety, mood lability and insomnia. As a psychological support, trazodone and vortioxetine were resumed, with venlafaxine continued at a modified dosage of 150 mg/24 h. Consequently, her sleep and mood improved, without any QTc prolongation.