Table 3.

CYP2B6 polymorphisms and adverse drug reactions reported amongst patients in various ethnicities.

Substrate	Subjects	N	CYP2B6 genotype	Predicted functional effect on CYP2B6 enzyme activity	Patient exposure to the drug	Frequency of allelic variants (%)	Population	Adverse drug reaction	References
Efavirenz	HIV/TB	185	CYP2B6*6/*6	↓ Activity	Higher exposure	45	Zimbabwe	Central nervous system adverse events(CNS) including insomnia, severe headaches, vivid nightmares, drowsiness, ataxia, dystonia and dizziness.	Patel and Patel, 2018
	HIV, TB-HIV co-infected patient	353	CYP2B6 516TT	↓ Activity	Higher exposure	31.6	Ethiopians	Anti-retroviral and anti-tuberculosis drug induced liver injury in TB-HIV co-infected patients.	Agency, 2017; Giardina et al., 2018
	HIV	285	CYP2B6 516TT	↓ Activity	Higher exposure	31	Ethiopians	Higher risk of drug induced liver injury!!break (DILI)	Agency, 2017; Schurig et al., 2018
	HIV	800	CYP2B6 516TT	↓ Activity	Higher exposure	48	Ghanaian	Neuropsychiatric toxicity	Stingl et al., 2013
	HIV	134	CYP2B6*6/*6	↓ Activity	Higher exposure	8.2	Thai	Increase risk of hepatotoxicity	Weinshilboum, 2003; Evans and Relling, 2004; Lynch and Price, 2007
	HIV/AIDS	1,147	CYP2B6 G516TT	↓ Activity	Higher exposure	38, 21.9	Mixed population European American, African American, Hispanics	Central nervous system toxicity	Zanger and Schwab, 2013
	HIV/AIDS	373	CYP2B6 516TT	↓ Activity	Higher exposure	30, 37	Mixed population (Black & White)	Central nervous system related effects!!break and 131 patients withdrew from therapy within the first 3 months	Nebert et al., 2013
	HIV	197	CYP2B6 516TT	↓ Activity	Higher exposure	30	Ugandans	Neuropsychiatric symptoms. High incidence of vivid dream, sleepwalking, insomnia and tactile hallucination	Thorn et al., 2010; Lonsdale et al., 2013
	HIV/TB patients	473	CYP2B6 516GT!!break CYP2B6 516TT	↓ Activity	Higher exposure	35.5	Tanzanians	Development of efavirenz based HAART liver injury	Agency, 2017; Desta et al., 2021
	HIV adults	142	CYP2B6 516GT!!break CYP2B6 516TT	↓ Activity	Higher exposure	32	South Africans	High efavirenz level associated with severed sleep disturbance	Rendic, 2002
	HIV	80	CYP2B6 516GT!!break CYP2B 516TT	↓ Activity	Higher exposure	43	South!!break Africans	Higher EFV concentration and early neuropsychiatric side effects (presence of hallucinations or psychotic episodes)	Hanna et al., 2000
	HIV	191	CYP2B6 516GT, CYP2B6 516TT	↓ Activity	Higher exposure	49	Mixed population (Caucasian 162, African 23, Asiantic four, others two)	CNS related symptoms such as disturbances in consciousness, mood disorders, headaches, sleep disturbances, cognitive and attention disturbances, eating disturbances and dizziness	Zanger et al., 2008
	HIV/AIDS	1330	CYP2B 516GT/TT	↓ Activity	Higher exposure	77, 25	Mixed population African ancestry (372), European ancestry (958)	Increase in cholesterol levels, Increased risk of neurotoxicity, CNS depression and neuropsychiatric disorders, Increased risk of fatigue and sleep disorder and Increased risk of hepatotoxicity and drug-induced liver injury	Sarfo et al., 2014
	HIV	32/90	CYP2B6 516TT	↓ Activity	Higher exposure	32	Mixed population	Increased likelihood of central nervous system disease	Kharasch and Greenblatt, 2019
	HIV	235	CYP2B6 516TT	↓ Activity	Higher exposure	26	Swiss	Neuropsychological toxicity	Chaivichacharn et al., 2020
	HIV patients	105	CYP2B6*1/*18, CYP2B6*18/*18	↓ Activity	Higher exposure	5.1	Mozambicans	Associated with severe cutaneous!!break adverse event such as Steven-Johnson syndrome and toxic epidermal necrolysis	Bank et al., 2019
Nevirapine	HIV	672	CYP2B6*18	↓ Activity	Higher exposure	18	Malawians!!break Ugandans	Hypersensitivity such as nevirapine induced-Stevens–Johnson syndrome (SJS)	Kim et al., 2017
	HIV	105	CYP2B6 516TT!!break CYP2B6 983CC	↓ Activity	Higher exposure	55.6!!break 18.5	Mozambicans	Patients with Nevirapine-induced SJS/toxic epidermal necrolysis (TEN)	Bank et al., 2019
Cyclophosphamide	non-Hodgkin's lymphoma	567	CYP2B6 516TT!!break CYP2B6 785AG (*4)	↓ Activity	Reduce exposure to 4-hydroxycy-cyclophosphamide	25.9!!break 32	Chinese	Lower risk of grade 2–4 toxicities and!!break poor treatment outcome	Bielinski et al., 2014
	Breast Cancer	230	CYP2B6*2 CYP2B6*4!!break CYP2B6*5!!break CYP2B6*9	↑ Activity	High exposure	227!!break 15!!break 30	Mixed population (European 97, South Asian 2, East Asian <1)	Leucopenia and neutropenia associated with dose delay	Hesse et al., 2004; Dolgin, 2011; Drozda et al., 2018
	Breast cancer	Case report	CYP2B6*7	↑ Activity	Higher exposure to 4-hydroxycy-cyclophosphamide	18.4	Han Chinese	Severe and prolonged hepatotoxicity	Ekins et al., 1998; Dolgin, 2011; Drozda et al., 2018
	Chronic lymphocytic leukemia (CLL)	428	CYP2B6*1/*6!!break CYP2B6*6/*6	↓ Activity	Reduced exposure	22	UK clinical trial	Decrease risk of drug toxicity. Toxicity included neutropenia, thrombocytopenia, anemia, mucositis, and alopecia	Lang et al., 2001
	Leukemia patients on stem cell transplant	107	CYP2B6*4!!break CYP2B6*2!!break CYP2B6*6 (donor GG genotype)	↑ activity	Higher exposure	53!!break 16, 50	Mixed population	Oral mucositis, (*4), hemorrhagic cystitis (*2),Veno-occlusive disease of the!!break liver (*6),	Wang et al., 2003a
Methadone	Breast cancer	166	CYP2B6 516GT,!!break CYP2B6516TT	↓ Activity	High exposure	27	Brazilian	High risk of severe levels of asthenia and arthralgia	Ekins et al., 1998; Wang et al., 2003b
	Fatalities cases due to methadone	380	CYP2B6*9 CYP2B6*5	↓ Activity	High exposure	27	Caucasians	Methadone fatalities	Lee et al., 2003; Wang et al., 2003b; Liptrott et al., 2009
	Opioid dependent males	148	CYP2B6*6	↓ Activity	High exposure	25.4	Malays	Lower pain threshold, increase severity of pain	Lee et al., 2003; Liptrott et al., 2009

↓, Decrease; ↑, Increase.