Multiple drugs

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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

A 51-year-old man developed pneumonia following treatment with clozapine for schizoaffective disorder. Subsequently, he developed delirium, repeated fall, increased incontinence, increased neutrophil level, increased monocyte level, increased high sensitivity-CRP level, low lymphocytes level, elevated clozapine level and clozapine toxicity following concurrent administration of clozapine, fenofibrate, linagliptin, metformin, pantoprazole, valproate semisodium and COVID-19 Vaccine Pfizer-BioNTech [not all dosages, indications and time to reaction onsets stated; routes not stated].

The man, who had schizoaffective disorder, had been receiving treatment with clozapine for more than 10 years. He was living at a mental health residential facility. He had hyperlipidaemia, type 2 diabetes mellitus, obesity class II, gastroesophageal reflux disease and obstructive sleep apnoea. His concurrent medications included linagliptin, metformin, pantoprazole, valproate sodium [divalproex] and fenofibrate. His medical history was significant for a past motor vehicle accident, with some residual gait impairment and infrequent incontinence. He had received yearly influenza vaccinations without any complication. Subsequently, he was hospitalised with pneumonia. At the time of admission, he was receiving clozapine at a dose of 500 mg/day. His clozapine level was noted to be 3984 nM/L and he was over-sedated. The pneumonia was considered to have developed secondary to clozapine.

The man's clozapine dose was decreased to 300 mg/day. He was treated with unspecified antibiotics. Thereafter, his pneumonia resolved.

Subsequently, he received COVID-19 Vaccine Pfizer-BioNTech [Pfizer-BioNTech vaccine for SARS-CoV-2] as a part of routine care. On day 4 of vaccination, he became delirious, fell repeatedly and was increasingly incontinent. Thus, he was admitted to hospital for further evaluation. On admission, his body temperature was 37.0°C, pulse was 129 beats/minute and BP was 151/86mm Hg. A chest radiograph revealed subsegmental atelectasis or scarring. He started receiving unspecified antibiotics empirically. At admission, his neutrophils level and monocytes level were increased, and lymphocyte level was low. In addition, his high sencitivity-CRP level was elevated. His clozapine level was noted to be elevated at 3296 nM/L. Also, C/D and C/N were high, which was consistent inhibition of CYP1A2 metabolism. He was diagnosed with clozapine toxicity secondary to concurrent administration of clozapine, fenofibrate, linagliptin, metformin, pantoprazole, valproate semisodium and COVID-19 Vaccine Pfizer-BioNTech (drug interaction). Clozapine was discontinued for 2 days. Six days after vaccination, his high sensitivity-CRP level and clozapine level decreased. He improved to his pre-vaccination level of symptoms and was discharged back to residential care.

Clozapine was resumed at a dose of 150mg on the evening of discharge. Three weeks following the discharge, the man remained clinically stable at that dose, with clozapine levels assessed weekly.