Red Yeast Rice

SeriousConcurrent prescription statin therapyGrade B

Additive HMG-CoA reductase inhibition; Substantially elevated myopathy and hepatotoxicity risk.

SeriousLactation / BreastfeedingGrade C

Monacolin K partitions into breast milk (class effect). Neonatal HMG-CoA reductase inhibition would impair lipid-dependent CNS development and myelination.

SeriousPersonal or family history of hereditary muscle disease (muscular dystrophy, myopathies, malignant hyperthermia)Grade C

Pre-existing myopathic conditions confer extreme sensitivity to statin-class myotoxicity. HMG-CoA inhibition further reduces mitochondrial CoQ10 and impairs electron transport chain in already vulnerable myocytes.

SeriousAge <18 years (children and adolescents)Grade C

No safety or efficacy data in pediatric populations. Cholesterol is essential for CNS maturation in adolescence.

SeriousPrior statin-induced hepatotoxicityGrade C

Chemical identity of monacolin K to lovastatin makes cross-hepatotoxicity expected. Resuming RYR after statin hepatotoxicity would constitute rechallenge with the same hepatotoxic moiety.

SeriousUse of RYR products from lots or brands implicated in nephrotoxicity cluster (Kobayashi Pharmaceutical Beni-koji, Japan 2024-2026)Grade C

Koshida 2025 documents 236+ hospitalization cases including acute tubular necrosis and Fanconi syndrome temporally associated with Kobayashi Pharmaceutical Beni-koji supplements (lot-specific). Mechanism distinct from citrinin.

ModerateAge >70 yearsGrade B

EFSA 2018 identified age >70 as an independent risk factor for monacolin-associated adverse events (myopathy, rhabdomyolysis, hepatotoxicity). Reduced CYP3A4 capacity, lower albumin (increased free fraction), polypharmacy CYP3A4 inhibitor burden, and impaired renal clearance of…

ModerateSignificant alcohol use disorder / chronic heavy alcohol consumptionGrade C

Chronic alcohol induces CYP2E1-mediated oxidative stress in hepatocytes, predisposing to statin hepatotoxicity. Alcohol also competes with monacolin K for hepatic metabolism and may unpredictably alter CYP3A4 activity.

ModerateRenal impairment � moderate to severe (eGFR <45 mL/min/1.73m�) or acute kidney injuryGrade C

Dual mechanism: (1) Rhabdomyolysis from any cause causes AKI via myoglobinuric cast nephropathy � renal impairment both increases myopathy risk (reduced clearance of metabolites) and worsens consequences of myopathy. (2) Japanese Beni-koji nephrotoxicity cluster (Koshida 2025):…

ModerateBiliary obstruction / cholestasisGrade C

Monacolin K is predominantly eliminated via biliary excretion (83.2% fecal, primarily biliary). Biliary obstruction would markedly impair elimination, increasing systemic exposure and hepatotoxicity risk.

ModerateHypothyroidism (untreated or under-treated)Grade C

Hypothyroidism is an independent risk factor for statin myopathy (class effect). Reduced muscle energy metabolism and impaired CK clearance compound monacolin K myotoxicity.

ModeratePre-operative / major surgery (within 1 week perioperative window)Grade D

Statin-class agents alter platelet function and coagulation cascade. Perioperative myopathy risk increased under general anesthesia due to altered muscle perfusion.

ModerateGastrointestinal malabsorption syndromes (celiac disease, short bowel syndrome, inflammatory bowel disease with significant mucosal damage)Grade D

Altered intestinal surface area and transit time produce unpredictable monacolin K absorption. May result in either sub-therapeutic levels (reduced absorption) or paradoxically increased bioavailability (if first-pass metabolism is also impaired due to portal hypertension or…

SeriousNefazodoneGrade B

Potent CYP3A4 inhibition � among strongest inhibitors; may increase lovastatin AUC >10-fold

SeriousGemfibrozilGrade B

Increases lovastatin acid AUC via glucuronidation inhibition (UGT2C8) and possibly CYP2C8 interaction; does not primarily act via CYP3A4.

SeriousVerapamilGrade B

Moderate CYP3A4 inhibition plus P-glycoprotein inhibition � dual mechanism; increases lovastatin AUC approximately 4-fold in controlled PK studies

SeriousAmiodaroneGrade B

SeriousGrapefruit juice (large quantities, >1 quart/day)Grade B

Intestinal CYP3A4 and P-glycoprotein inhibition via furanocoumarins (bergamottin, dihydroxybergamottin); increases pre-systemic monacolin K absorption.

SeriousPrescription statins (any HMG-CoA reductase inhibitor)Grade C

Additive pharmacodynamic HMG-CoA reductase inhibition; combined myopathy risk exceeds either agent alone.

ModerateNiacin (nicotinic acid) at lipid-lowering doses (=1g/day)Grade C

Additive pharmacodynamic myopathy risk; may involve mitochondrial CoQ10 depletion

ModerateBerberineGrade C

CYP3A4 inhibition and P-glycoprotein inhibition documented in vitro and in clinical PK studies; increases effective monacolin K systemic exposure.

ModerateColchicineGrade C

Colchicine is both a CYP3A4 and P-glycoprotein substrate; RYR P-gp inhibition may increase colchicine exposure.

ModerateWarfarin (and other vitamin K antagonists)Grade C

Statins (including lovastatin/monacolin K) inhibit CYP2C9-mediated warfarin metabolism to a modest degree; additive anticoagulant potentiation has been reported.