title: Sildenafil and furosemide associated ototoxicity: consideration of drug-drug interactions, synergy, and broader clinical relevance.
abstract: Drug-induced ototoxicity, particularly those involving phosphodiesterase type 5 (PDE-5) inhibitors, is considered to be rare and to our knowledge such an adverse effect has not been reported in Canada. Here we present a case of a 77-year old man initiated on a sildenfil regimen for the treatment of pulmonary hypertension, who developed sudden bilateral hearing loss after taking sildenafil, in the setting of high dose furosemide and diltiazem. We outline the likely interplay of patient characteristics, drug synergy and drug-drug interactions in the development of his ototoxicity. Importantly, given the extent and popularity of PDE-5 inhibitors for erectile dysfunction as well as a newer therapeutic option for pulmonary hypertension, clinicians should be aware of the risk for drug-induced ototoxicity, particularly in the setting of concomitant loop diuretics and CYP3A4 inhibiting medications.
authors.affiliation: Department of Medicine, London Health Sciences Centre, Schulich School of Medicine and Dentistry, Western University, London, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Skeith
authors.forename: Cory
authors.initials: C
authors.lastname: Yamashita
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
authors.forename: Donald
authors.initials: D
authors.lastname: Farquhar
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
mesh_terms: D000368:Aged; D002170:Canada; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004232:Diuretics; D004791:Enzyme Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D005665:Furosemide; D000068677:Sildenafil Citrate; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D004110:Diltiazem