Rhabdomyolysis and pancreatitis associated with coadministration of danazol 600 mg/d and lovastatin 40 mg/d.
BACKGROUND
Danazol is a steroid analogue with anabolic and androgenic effects and is indicated for the treatment of endometriosis, fibrocystic diseases of the breast, and hereditary angioedema. Lovastatin has been prescribed to lower total cholesterol and low-density lipoprotein cholesterol, reducing cardiovascular-related morbidity and mortality in patients with hypercholesterolemia. As monotherapies, both danazol and lovastatin have been reported to induce myopathy and pancreatitis.


METHODS
A 59-year-old Asian woman (height, 155 cm; weight, 54 kg; and body mass index, 22.5 kg/m2) presented to the outpatient neurology clinic with acute progressive quadriparesis and generalized myalgia (without focal sensory loss, numbness, dizziness, diplopia, dysarthria, dysphagia, or sphincter incontinence), lasting for 5 days. She was admitted to the National Cheng Kung University Hospital, Tainan, Taiwan. The patient's medical history revealed multiple comorbidities (eg, end-stage renal disease, hypertension, diabetes mellitus) for which she was receiving concomitant medication. Her medication history revealed that at the time the patient presented, she was also receiving calcium bicarbonate 1500 mg/d, labetalol 100 mg/d, and glipizide 10 mg/d in the treatment of her other comorbid illnesses. The patient was also receiving alprazolam 0.5 mg/d for insomnia. Her medical records also revealed that lovastatin 40 mg/d (a particularly high dose and not recommended) had been administered for 7 weeks, and danazol 600 mg/d was added ( approximately 15 days later) to treat thrombocytopenia due to hypoplastic bone marrow. Laboratory findings revealed elevated creatine kinase (68,193 U/L), elevated pancreatic enzymes (amylase/lipase, 361/2788 U/L), and elevated liver enzymes (aspartate/alanine aminotransferase, 1496/1493 U/L), consistent with rhabdomyolysis and pancreatitis. After discontinuation of both drugs, the symptoms improved 5 days after admission and completely disappeared 1 month after admission. In addition, laboratory abnormalities completely normalized approximately 2 months after admission. Danazol was resumed to treat persistent thrombocytopenia, while lovastatin was replaced with ezetimibe 10 mg QD to treat high cholesterol (dyslipidemia).


CONCLUSIONS
The coadministration of high-dose lovastatin and danazol was probably associated with rhabdomyolysis and pancreatitis in this patient with multiple underlying comorbidities for which concomitant medications were being administered.
Hsieh
Cheng-Yang
CY
Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chen
Chih-Hung
CH
D000924:Anticholesteremic Agents / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000150:complications; D003613:Danazol / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008148:Lovastatin / Q000009:adverse effects*; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced*; D012206:Rhabdomyolysis / Q000139:chemically induced*; D013921:Thrombocytopenia / Q000188:drug therapy / Q000209:etiology
D000924:Anticholesteremic Agents; D008148:Lovastatin; D003613:Danazol