Summary

• A pharmacokinetic (PK) study assessed the effects of coadministration of a nasal decongestant (oxymetazoline), administered 1 hour prior to esketamine (ESK) dosing, and a nasal corticosteroid (mometasone furoate). No significant differences in the PK of ESK were observed.^1,2
• Patients should be instructed to blow their nose before using the first ESK nasal spray device only.³

Clinical DatA

PK Study

Zannikos et al (2023)² conducted a single-center, open-label PK study to characterize the effects of coadministration of oxymetazoline or mometasone on the PK of ESK nasal spray in patients with allergic rhinitis or healthy subjects, respectively.

Twenty-two patients with a history of moderate allergic rhinitis were enrolled in cohort 1, a 2-way crossover study, and were exposed to pollen prior to randomization to one of two treatment sequences to trigger symptoms of allergic rhinitis. Both sequences had 2 periods separated by a 5- to 10-day washout interval. Period 1 of one sequence involved administration of ESK 56 mg. Period 2 of the same sequence involved 2 sprays of oxymetazoline 0.05% solution in each nostril 1 hour before another dose of ESK 56 mg. This was reversed in the treatment scheme for the other sequence.

Twenty-four healthy subjects were enrolled in cohort 2, a 2-period fixed-sequence study, and received ESK 56 mg on day 1 of period 1, mometasone 200 μg nasal suspension         (2 sprays of 50 µg/spray mometasone suspension in each nostril) from day 1 to day 16 of period 2, and ESK 56 mg on day 16 of period 2, 1 hour after administration of mometasone.

The 90% confidence intervals for the geometric mean ratios of maximum serum concentration (C_max), area under the curve up to the last measurable concentration (AUC_last), and area under the curve for total drug exposure across time (AUC_∞) were contained within the bioequivalence range between 0.80-1.25 for when ESK was administered after oxymetazoline or mometasone treatment compared with when ESK was administered alone.

The study demonstrated that the PK of ESK was similar in patients experiencing symptoms of allergic rhinitis (with intranasal administration of oxymetazoline) and healthy subjects.  Furthermore, daily intranasal administration of mometasone had no effects on the PK of ESK 56 mg nasal spray in healthy subjects.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 23 September 2024.