Revefenacin (YupelriTM) - Theravance Biopharma and Mylan

George Cullina, Pharm.D., Cashwise Clinic Pharmacy / ACMC

Indication: Revefenacin inhalation solution is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Mechanism of Action: Revefenacin is a long-acting muscarinic antagonist (LAMA), with similar affinity for both the M1 and M5 subtypes of muscarinic receptors. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor in smooth muscle leading to bronchodilation.

Dosage and Administration: Revefenacin is a 175 mcg per 3 mL inhalation solution delivered via nebulizer once daily. No dosage adjustment is required for geriatric patients or patients with renal impairment.

Effectiveness: During two 12-week randomized, double-blind, placebo-controlled trials, forced expiratory volume (FEV1) was assessed in patients with moderate to very severe COPD. Pooled data showed that, compared with placebo, patients treated with once daily revefenacin had greater improvements in the 24 hour change from baseline in trough FEV1 on day 85 and the overall treatment effect in trough FEV1 over 12 weeks. In another randomized, double-blind study, 207 patients with moderate to very severe COPD and suboptimal peak inspiratory flow rates (PIFR < 60 L/min) were randomized to receive revefenacin 175 mcg once daily via nebulizer or tiotropium once daily via HandiHaler® for 28 days. On day 29, revefenacin and tiotropium effectively improved trough FEV1 and forced vital capacity (FVC) from baseline. In a prespecified subgroup analysis, revefenacin significantly improved trough FEV1 and FVC (Δ trough FEV1: 47.3 mL, P=0.0302; Δ trough FVC: 99.9 mL, P=0.0407) from baseline compared with tiotropium in patients with severe to very severe COPD.

Safety:

Adverse reactions: Cough, headache, back pain, nasopharyngitis, and upper respiratory infections
Serious adverse reactions: Paradoxical bronchospasm
Avoid use: Patients with acutely deteriorating or potentially life-threatening episodes of COPD. Use with caution in patients with narrow-angle glaucoma or urinary retention.
Contraindications: Patients with hypersensitivity to revefenacin or any component of this product.

Place in Therapy: Revefenacin inhalation solution via nebulizer is similar in efficacy to tiotropium (SpirivaTM) via Handihaler® in patients with moderate to very severe COPD. Therefore, it is reasonable to use in patients that have difficulty operating the Handihaler® device or with proper inhalation technique. Revefenacin was shown to be superior to tiotropium in severe and very severe COPD patients, demonstrated by the significant improvement in FEV1 and FVC, however specific patient-oriented outcomes were not studied. Revefenacin maybe preferred over tiotropium in severe to very severe COPD patients. The cost of acquisition via Mckesson online warehouse was found to be $995 for a box of 30 vials (90 mL), which is a one month supply. A 30 day supply of SpirivaTM (either the Handihaler® or Respimat®) are both $414.87.

References:

  1. Yupelri (revefenacin) [package insert]. Morgantown, WV: Mylan Specialty L.P.; 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6dfebf04-7c90-436a-9b16-750d3c1ee0a6 Accessed February 15, 2019.  

  2. Heo, Young-A. Revefenacin: first global approval. Drugs. 2018;79(1):85-91. doi:10.1007/s40265-018-1036-x.

  3. Mahler D, Ohar J, Barnes C, et al. Efficacy of revefenacin by nebulization and tiotropium by Handihaler in subjects with COPD and suboptimal peak inspiratory flow rates (PIFR). Chest. 2018;154(4). doi:10.1016/j.chest.2018.08.663.

  4. Medical Supplies, Pharmaceuticals & Healthcare Solutions. McKesson. https://www.mckesson.com/. Updated February 18, 2019. Accessed February 18, 2019.