Table 4.

Characteristics of the included studies involving patients with drug-drug interactions

Author/year	Title	Diagnosis	N	Treatment	Type of interaction	Clinical outcome	Patient management	Drug Interaction probability scale (DIPS)
Whiskey et al. 2018 (Whiskey et al. 2018)	Clozapine, HIV and neutropenia: a case report	Schizophrenia and HIV	1	CLZ 450 mg/day RIT 100 mg/day VAL 500 mg/day LMV and ZDV (not dose data)	Interaction CYP 3A4, CYP 2D6, CYP 1A2 and CYP 2C19	Neutropenia attributable to the action and/or interaction of drugs. Unable to conclude whether due to the study variable (CLZ and RIT)	Evaluated the possibility of using GCSF with CLZ VAL removal Changed antiretrovirals (Truvada and darunavir) and kept RIT	Possible
Geraci et al. 2010 (Geraci et al. 2010)	Antipsychotic-induced priapism in an HIV patient: a cytochrome P450-mediated drug interaction	HIV	1	LPV 200 mg/RIT 50 mg/day QUE 300 mg/day	Interaction CYP 2D6 and CYP 3A4	Priapism Increased levels of psychotropic drugs	Anesthetized locally with 1% lidocaine and epinephrine and irrigated with dilute ephedrine and saline	Highly probable
Aung et al. 2010 (Aung et al. 2010)	Increased aripiprazole concentrations in an HIV-positive male concurrently taking duloxetine, darunavir, and ritonavir	HIV and anxiety-depressive syndrome	1	ARI 50 mg/day RIT 100 mg/day	Interaction CYP 2D6 and CYP 3A4	NMS Increased levels of antipsychotic drugs	Disruption of the neuroleptics Intensive fluid therapy administration	Probable
Pollack et al. 2009 (Pollack et al. 2009)	Clinically significant adverse events from a drug interaction between quetiapine and atazanavir-ritonavir in two patients	First patient: HIV + BD Second patient: HIV, anxiety disorder and substance abuse disorder	2	QUE400/day RIT100/day	Interaction CYP 3A4	Patient 1: Increase of 22 kg in 6 months. Glucose level: 259 mg/dL Patient 2: delirium	Patient 1: RIT was replaced with abacavir and the patient lost 5 kilograms per month and his serum glucose level had normalized Patient 2: QUE stopped and resolution of mental status	Probable
Jover et al. 2002 (Jover et al. 2002)	Reversible coma caused by risperidone-ritonavir interaction	HIV and manic episode	1	RIS 3 mg/day RIT200 mg/day	Interaction CYP 2D6 and CYP 3A4	Coma	APs stopped 24 h later, neurological status returned to baseline and manic symptoms gradually reappeared	Probable
Kelly et al. 2002 (Kelly et al. 2002)	Extrapyramidal symptoms with ritonavir/indinavir plus risperidone	HIV and Tourette’s syndrome	1	RIS 4 mg/day RIT 400 mg /day	Interaction of both drugs via CYP 2D6	Acute dystonia and tremor exacerbation	APs stopped 3 days later the symptoms improved significantly	Highly probable
Lee et al. 2000 (Lee et al. 2000)	Neuroleptic malignant syndrome associated with use of risperidone, ritonavir, and indinavir: a case report	HIV and acute psychotic episode	1	RIS 1.5 mg/day RIT 400 mg/day	Interaction Track CYP 2D6 and CYP 3A4	NMS	RIS and RIT were discontinued Dantrolene and bromocriptine were started. Clinical remission 2 weeks later	Probable

ARI aripiprazole; BD bipolar disorder; CLZ clozapine; GCSF granulocyte stimulating factor; LMV lamivudine; LPV lopinavir; NMS neuroleptic malignant syndrome; QUE quetiapine; RIT ritonavir; RIS risperidone; VAL valproic acid; ZDV zidovudine