Table 5.
Summary of AEs reported in key randomized controlled trials of RYR in subjects with dyslipidemia.
| Study | Number of Subjects | Type of AE | n (%) | ||||
|---|---|---|---|---|---|---|---|
| N (RYR Dose; MK [Lovastatin] Dose) | Control | RYR | Control | ||||
| Placebo comparator | |||||||
| Heber, 1999 [44] | 42 (2.4 g/d; 4.8 mg/d) | 41 | Serious Total |
0 (0) 1 (2) |
0 (0) 3 (7) |
||
| Musculoskeletal chest pain | 1 (2) | 0 (0) | |||||
| Headache | 0 (0) | 1 (2) | |||||
| Pneumonia | 0 (0) | 1 (2) | |||||
| Rash/pruritus/skin allergy | 0 (0) | 1 (2) | |||||
| Lin, 2005 [47] | 37 (1.2 g/d; 11.4 mg/d) | 38 | Serious Breast carcinoma (not related to RYR) Total |
1 (3) 1 (3) 21 (57) |
0 (0) 28 (74) |
||
| Increased CPK | 1 (3) | 0 (0) | |||||
| Increased ALT | 1 (3) | 0 (0) | |||||
| Diarrhea | 0 (0) | 1 (3) | |||||
| Nausea | 0 (0) | 1 (3) | |||||
| Leukopenia | 0 (0) | 1 (3) | |||||
| LDH increase | 1 (3) | 0 (0) | |||||
| Becker, 2009 [48] a | 31 (3.6 g/d; 6 mg/d) | 31 | Total | NR | NR | ||
| Serious | NR | NR | |||||
| Myalgia | 2 (6) | 1 (3) | |||||
| Loose stools | 1 (3) | 0 (0) | |||||
| Dizziness | 1 (3) | 0 (0) | |||||
| Bogsrud, 2010 [49] | 22 (4 capsules; 7.2 mg/d) | 20 | Serious Total |
0 (0) 8 (36) |
0 (0) 1 (5) |
||
| Back pain | 1 (5) | 0 (0) | |||||
| Increased CPK | 1 (5) | 0 (0) | |||||
| Diarrhea | 2 (9) | 0 (0) | |||||
| Flatulence | 1 (5) | 1 (5) | |||||
| Crohn’s disease | 1 (5) | 0 (0) | |||||
| General discomfort | 1 (5) | 0 (0) | |||||
| Influenza | 1 (5) | 0 (0) | |||||
| Verhoeven, 2013 [51] | 31 (2 capsules/day; 10.05 mg/d) | 21 | Serious Total |
NR NR |
NR NR |
||
| Muscle stiffness | 2 (6) | 0 (0) | |||||
| Muscle cramps | 3 (10) | 1 (5) | |||||
| Myalgia | 4 (13) | 2 (10) | |||||
| Increased CPK | 5 (16) | 3 (14) | |||||
| Liver pain | 0 (0) | 1 (5) | |||||
| Belches | 1 (3) | 0 (0) | |||||
| Erectile dysfunction | 0 (0) | 1 (5) | |||||
| Insomnia | 1 (3) | 1 (5) | |||||
| Pruritus | 0 (0) | 1 (5) | |||||
| Moriarty, 2014 [52] b | XZK (1.2 g/d) n = 36 |
XZK (2.4 g/d) n = 42 |
37 | Serious Fracture, extremity (not related to RYR) Pulmonary embolism (not related to RYR) Thyroid cancer (not related to RYR) Total |
1.2 g/d 0 (0) 0 (0) 1 (3) 17 (47) |
2.4 g/d 1 (2) 1 (2) 0 (0) 22 (52) |
PBO 0 (0) 0 (0) 0 (0) 19 (51) |
| Musculoskeletal/connective tissue disorders | 4 (11) | 5 (12) | 1 (3) | ||||
| - Muscle spasm | 0 (0) | 2 (5) | 0 (0) | ||||
| - Myalgia | 1 (3) | 2 (5) | 0 (0) | ||||
| - Jaw pain | 1 (3) | 0 (0) | 0 (0) | ||||
| Investigations/laboratory abnormalities | 2 (6) | 1 (2) | 6 (16) | ||||
| - Increased CPK | 0 (0) | 0 (0) | 2 (5) | ||||
| - Increased ALT | 0 (0) | 0 (0) | 2 (5) | ||||
| - Increased AST - Increased leukocyte count |
0 (0) 2 (6) |
0 (0) 0 (0) |
2 (5) 0 (0) |
||||
| Gastrointestinal disorders | 5 (14) | 10 (24) | 10 (27) | ||||
| - Diarrhea | 2 (6) | 0 (0) | 1 (3) | ||||
| - Dyspepsia | 3 (8) | 1 (2) | 1 (3) | ||||
| - Nausea | 0 (0) | 2 (5) | 2 (5) | ||||
| - Abdominal discomfort | 0 (0) | 0 (0) | 2 (5) | ||||
| - Epigastric pain | 1 (3) | 0 (0) | 0 (0) | ||||
| Nervous system disorders | 1 (3) | 3 (7) | 3 (8) | ||||
| - Headache | 1 (3) | 2 (5) | 2 (5) | ||||
| Infections | 4 (11) | 5 (12) | 4 (11) | ||||
| - URTI | 0 (0) | 2 (5) | 3 (8) | ||||
| Rash | 1 (3) | 0 (0) | 0 (0) | ||||
| Skin flushing | 0 (0) | 0 (0) | 1 (3) | ||||
| Wang, 2019 [54] c | MK-RYR (400 mg/d; 8 mg/d) n = 23 |
GABA-RYR (335 mg/d; NA) n = 23 |
23 | Serious Total Elevated creatinine Increased ALT Increased AST |
0 (0) 1 (4) 0 (0) 1 (4) 1 (4) |
0 (0) 1 (4) 0 (0) 1 (4) 1 (4) |
0 (0) 3 (13) 1 (4) 0 (0) 0 (0) |
| Poor general health | 0 (0) | 0 (0) | 1 (4) | ||||
| Anxiety | 1 (4) | 0 (0) | 0 (0) | ||||
| Skin allergy | 0 (0) | 0 (0) | 1 (4) | ||||
| Minamizuka, 2021 [55] | 10 (200 mg/d; 2 mg/d) | 8 | Serious | NR | NR | ||
| Skin rash | 0 (0) | 0 (0) | |||||
| Muscle pain | 0 (0) | 0 (0) | |||||
| Total | 0 (0) | 0 (0) | |||||
| Statin comparator | |||||||
| Xiaobin, 2007 [62] | XZK; NA | ATV; NA n = 130 overall |
NA | NA | |||
| Gheith, 2008 [61] | RYR 1.2 g/d for 1 month then 600 mg/d n = 20 | FLV 20 mg/d n = 30 PBO n = 22 |
NR | NR | |||
| Liu, 2011 [66] | LRRMP (350 mg/d; NA) n = 20; XZK (1.2 g/d; NA) n = 20 | LOV 20 mg/d n = 20 |
Serious Total |
0 (0) NA |
1 (5) d NA |
||
| Li, 2011 [65] | XZK (1.2 g/d; NA) n = 32 | LOV 40 mg/d n = 32 |
NA | NA | |||
| Halbert, 2010 [63] | RYR (4.8 g/d; 9.96 mg/d) n = 21 | PRV 40 mg/d n = 22 |
Serious Total |
NR NR |
NR NR |
||
| Persistent myalgia only | |||||||
| - Generalized | 0 (0) | 3 (14) | |||||
| - Local | 2 (10) | 1 (5) | |||||
| - Local and generalized | 2 (10) | 4 (18) | |||||
| Persistent and intermittent myalgia | |||||||
| - Generalized | 1 (5) | 6 (27) | |||||
| - Local | 4 (19) | 3 (14) | |||||
| - Local and generalized | 5 (24) | 8 (36) | |||||
| Muscle weakness | 1 (5) | 1 (5) | |||||
| Abdominal gas, bloating | 2 (10) | 0 (0) | |||||
| Alopecia | 2 (10) | 0 (0) | |||||
| Arthralgia | 1 (5) | 1 (5) | |||||
| Back pain | 5 (24) | 6 (27) | |||||
| Diarrhea | 2 (10) | 0 (0) | |||||
| Dizziness | 0 (0) | 2 (9) | |||||
| Dyspepsia | 1 (5) | 0 | |||||
| Fatigue | 0 | 3 (14) | |||||
| Fracture, extremity | 1 (5) | 0 | |||||
| Headache | 2 (10) | 2 (9) | |||||
| Motor co-ordination decreased, left hand | 0 | 1 (5) | |||||
| Ruscica, 2014 [59] | RYR (200 mg/d; 3 mg/d) n = 30 | PRV 10 mg/d n = 30 |
Serious Total |
NR NR |
NR NR |
||
| Marazzi, 2017 [60] | RYR (200 mg/d; 3 mg/d) n = 50 | SMV 10–20 mg/d or ATV 5–10 mg/d or RSV 5 mg/d n = 50 |
Serious | NR | NR | ||
| Total | NR | NR | |||||
| Musculoskeletal discomfort | 3 (6) | 3 (6) | |||||
| Hepatobiliary disorders | 0 (0) | 0 (0) | |||||
| Gastrointestinal disorders | 2 (4) | 1 (2) | |||||
| Metabolic disorders | 0 (0) | 0 (0) | |||||
| Kou, 1997 [56] | XZK (1.2 g/d; NA) n = 53 | SMV 10 mg/d n = 55 |
Severe Total |
NA NA |
NA NA |
||
| Chen, 2002 [57] | XZK (1.2 g/d; NA) n = NA e | SMV 10 mg/d n = NA e |
Serious Total |
0 (0) 0 (0) |
0 (0) 0 (0) |
||
| Xue, 2017 [64] | RYR (1.2 g/d; NA) n = 27 | SMV 20 mg/d n = 33 |
Serious Total |
0 (0) 0 (0) |
0 (0) 0 (0) |
||
| Cui, 2015 [58] | XZK 600 mg BID n = 30 | SMV 20 mg QD n = 30 SMV stopped and restarted at 20 mg QD n = 30 |
NR | NR | |||
a AEs leading to study discontinuation; b AEs leading to discontinuations and/or AEs reported in ≥2 subjects; c Report described AEs leading to discontinuation; d One patient dropped out due to transaminase elevation; listed as SAE here; e Total number of patients in study = 65. AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATV = atorvastatin; BID = twice daily; CPK = creatine phosphokinase; FLV = fluvastatin; GABA = gamma-aminobutyric acid-rich RYR; LDH = lactate dehydrogenase; LRRMP = lipid-reducing red rice minute powder; LOV = lovastatin; MK = monacolin K; NA = not available; NR = not reported; QD = once daily; PRV = pravastatin; RSV = rosuvastatin; RYR = red yeast rice; SAE = serious adverse event; SMV = simvastatin; URTI = upper respiratory tract infection; XZK = Xuezhikang.