Ciprofloxacin-rasagiline drug interaction leading to dopaminergic effects.

Rasagiline, indicated for Parkinson disease (PD), is metabolized in the liver via the cytochrome P450 (CYP) system. Countless other medications including ciprofl oxacin are also metabolized in this pathway. Without proper dose adjustment, this concurrent metabolism leads to increased rasagiline blood concentrations and dopamine levels, causing adverse reactions. Rasagiline, a monoamine oxidase-B inhibitor, is indicated as monotherapy or adjunct therapy for the treatment of PD. It is eliminated from the body through hepatic metabolism via the cytochrome P4501A2 (CYP1A2) pathway and requires a dose adjustment for patients with hepatic impairment or for those taking concomitant medications that inhibit CYP1A2. Numerous medications inhibit the CYP1A2 enzyme, including ciprofl oxacin, fl uvoxamine, amiodarone, and cimetidine. Ciprofl oxacin, as well as fl uoroquinolones as a class, should not be used as fi rst-line antibiotics due to numerous adverse reactions and drug interactions. The FDA released a statement in 2016 that the toxicities of fl uoroquinolones generally outweigh the benefi ts in patients with uncomplicated infections. In addition, the FDA expanded on the statement that fl uoroquinolones should not be used if there are other fi rst-line therapies available for certain infections, such as uncomplicated urinary tract infections (UTIs), acute bacterial sinusitis, and acute bacterial exacerbation of chronic bronchitis. In the event that rasagiline is used concomitantly with ciprofl oxacin or other CYP1A2 inhibitors, it is recommended that the rasagiline dose be halved. This recommendation is due to an increased serum concentration of rasagiline, as this boost in concentration could lead to increased dopaminergic effects, such as dyskinesia, ataxia, and paresthesias. A pharmacokinetic study in healthy volunteers (n = 12) found that when rasagiline at 2 mg/day was administered with ciprofl oxacin at 500 mg every 12 hours, the area under the curve of rasagiline increased by 83%. While the concentration was increased greatly, there was no change in the elimination half-life of rasagiline. Although the risk of the interaction is stated in the package insert of rasagiline, minimal reports in the literature have identifi ed the consequences of the drug interaction between ciprofl oxacin and rasagiline. The following case report reviews the clinical implications of the drug-drug interaction between rasagiline and ciprofl oxacin. ■ Case study Mr. C, a 69-year-old Black male, presented to the ED with a chief complaint of weakness, fatigue, and back pain. Upon arrival, Mr. C was febrile up to 100.4° F (38° C), heart rate of 69 beats/minute, respirations 18 breaths/min, BP 127/68 mm Hg, white blood cell (WBC) count of 12.6 x 10/L, and oxygen saturation of 97% on room air. The computerized tomography abdomen and pelvis from the ED showed emphysematous pyelonephritis, hydronephrosis, and nephrolithiasis. Mr. C’s medical history includes nephrectomy of the left kidney due to renal cell carcinoma in 2008, a right kidney transplant due to end-stage renal disease in August 2017, transplant nephrolithiasis status post lithotripsy with stone removal in July 2018, PD, hypertension, transient ischemic attack, and recurrent UTIs. Due to his history of recurrent UTIs, Mr. C was recently started on prophylactic ciprofl oxacin 500 mg three times weekly on Mondays, Wednesdays, and Fridays. Prior to starting ciprofl oxacin for recurrent UTIs, the patient had good control of his PD with his current regimen. Mr. C’s home medications included rasagiline 1 mg daily, allopurinol 100 mg daily, carbidopa-levodopa 25 mg to 100 mg BID, carvedilol 6.25 mg BID, furosemide 80 mg BID, insulin glargine 10 units nightly,