Study	Treatment	Total number of participants reporting ≥ 1adverse event	Serious adverse events	Total all‐cause withdrawals	Withdrawals due to adverse events
Arambasik 2013	Treatment group (17 participants; 17 VOC episodes): IV hydromorphone 2 mg 15 min later: IV hydromorphone 2 mg + IV ketamine 6.2 mg/kg Control group (20 participants; 20 VOC episodes): IV hydromorphone 2 mg 15 min later: IV hydromorphone 2 mg + IV saline placebo	Ketamine: no data Placebo: no data	Ketamine: no data Placebo: no data	Ketamine: no data Placebo: no data	Ketamine: no data Placebo: no data
Bartolucci 2009	Ketoprofen (33 VOC episodes): Days 1 and 2: continuous IV infusion ketoprofen 300 mg/day, 2 days Days 3–5: 100 mg oral ketoprofen, every 8 hr, 3 days Placebo (33 VOC episodes): Days 1 and 2: physiological saline continuous IV infusion, 2 days Days 3–5: oral placebo tablet, every 8 hr, 3 days	Ketoprofen: 16/33 Placebo: 19/33	Ketoprofen: 1/33 Placebo: 2/33	Ketoprofen: unclear Placebo: unclear	Ketoprofen: 1/33 Placebo: 1/33
Benjamin 1986	Cetiedil 0.2 (16 participants; 16 VOC episodes): 0.2 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Cetiedil 0.3 (18 participants; 18 VOC episodes): 0.3 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Cetiedil 0.4 (13 participants; 13 VOC episodes): 0.4 mg/kg IV infusion, every 8 hr, 4 days, total 12 doses Placebo (16 participants; 16 VOC episodes): saline IV infusion, every 8 hr, 4 days, total 12 doses	Cetiedil 0.2 mg: 2/17 Cetiedil 0.3 mg: 9/18 Cetiedil 0.4 mg: 8/14 Placebo: 8/18 "The incidence of adverse effects was similar for the cetiedil 0.3, 0.4 and placebo groups, and significantly lower for the cetiedil 0.2 group (p = 0.04). The most commonly reported AE were headache and nausea and committing, and dry mouth."	Cetiedil 0.2 mg: 0/16 Cetiedil 0.3 mg: 0/18 Cetiedil 0.4 mg: 0/13 Placebo: 0/16	Cetiedil 0.2 mg: unclear Cetiedil 0.3 mg: unclear Cetiedil 0.4 mg: unclear Placebo: unclear	Cetiedil 0.2 mg: unclear Cetiedil 0.3 mg: unclear Cetiedil 0.4 mg: unclear Placebo: unclear
De Franceschi 2016	Treatment group VOC1 (KTM) (10 participants; 20 VOC episodes): continuous IV infusion ketorolac 0.86 mg/kg/day + tramadol 7.2 mg/kg/day + metoclopramide 0.57 mg/kg/day, for maximum of 72 hr Treatment group VOC2 (KT MF) (10 participants; 20 VOC episodes): continuous IV infusion ketorolac 0.86 mg/kg/day + tramadol 7.2 mg/kg/day + metoclopramide 0.57 mg/kg/day + fentanyl buccal single tablet 100 μg after 3 hr from beginning of multimodal analgesia, for maximum of 72 hr	KTM: 0/20 KTMF: 0/20	KTM: 0/20 KTMF: 0/20	KTM: 0/20 KTMF: 0/20	KTM: 0/20 KTMF: 0/20
Gonzalez 1988	Butorphanol (9 participants; 12 VOC episodes): IM butorphanol 2 mg, repeated within 30–60 min until pain relief obtained, repeat every 2–4 hr, until discharge. Morphine (9 participants; 12 VOC episodes): IM morphine 6 mg, repeat within 30–60 min until pain relief obtained, repeated every 2–4 hr, until discharge	Butorphanol: 4/12 (nausea and vomiting) Morphine: 4/12 (nausea and vomiting)	Butorphanol: 0/12 Morphine: 0/12	Butorphanol: no data Morphine: no data	Butorphanol: no data Morphine: no data
Perlin 1994	Ketorolac (10 participants; 10 VOC episodes): bolus ketorolac 30 mg; continuous IV infusion ketorolac 120 mg, 5 mg/hr, total dose 150 mg (on first day), maximum 120 mg/day, up to 5 days Placebo (11 participants; 11 VOC episodes): bolus saline; continuous IV infusion saline, up to 5 days	Ketorolac: unclear Placebo: unclear	Ketorolac: 0/10 Placebo: 0/11	Ketorolac: 1/10 Placebo: 0/11	Ketorolac: 0/10 Placebo: 0/11
Qari 2007	Tinzaparin (127 participants; 127 VOC episodes): subcutaneous tinzaparin 175 IU/kg, once daily, 7 days Placebo (126 participants; 126 VOC episodes): subcutaneous placebo, once daily, 7 days	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data	Tinzaparin: no data Placebo: no data
Rehmani 2013	Morphine (54 participants; 54 VOC episodes): IV morphine 0.1 mg/kg, single dose Paracetamol (52 participants; 52 VOC episodes): IV paracetamol 1 g, single dose	Morphine: 5/54 Paracetamol: 3/52	Morphine: 0/54 Paracetamol: 0/52	Morphine: no data Paracetamol: no data	Morphine: no data Paracetamol: no data
Wright 1992	Ketorolac (12 VOC episodes): IM ketorolac 60 mg, single dose Placebo (12 VOC episodes): IM saline, single dose	Ketorolac: 0/12 Placebo: 0/12	Ketorolac: 0/12 Placebo: 0/12	Ketorolac: 0/12 Placebo: 0/12	Ketorolac: 0/12 Placebo: 0/12
CPS: categorical pain scale; hr: hour; IM: intramuscular; IQR: interquartile range; IV: intravenous; KTM: ketorolac + tramadol + metoclopramide; KTMF: ketorolac + tramadol + metoclopramide + fentanyl;VAS: visual analogue scale; VCS: visual categorical score; VOC: vaso‐occlusive crisis; VRS: verbal rating scale.