Pilocarpine Hydrochloride

QLOSI is indicated for the treatment of presbyopia in adults. QLOSI is a cholinergic agonist indicated for the treatment of presbyopia in adults. ( 1 )

QLOSI is a clear, colorless to slightly yellowish ophthalmic solution containing pilocarpine hydrochloride 0.4% (4 mg /mL) in a single-patient-use vial. Ophthalmic solution: pilocarpine hydrochloride 0.4% (4 mg/mL) in a single-patient-use vial. ( 3 )

QLOSI is contraindicated in patients with known hypersensitivity to the active ingredient or to any of the excipients. Hypersensitivity ( 4 )

Blurred Vision : Advise patients to not drive or operate machinery if vision is not clear (e.g., blurred vision). Exercise caution in night driving and other hazardous occupations in poor illumination. ( 5.1 ) Risk of Retinal Detachment : Rare cases of retinal detachment have been reported with miotics. Examination of the retina is advised in all patients prior to initiation of therapy. Advise patients to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss. ( 5.2 ) Iritis : Caution is advised in patients with iritis. ( 5.3 )

5.1 Blurred Vision Miotics, including QLOSI, may cause accommodative spasm. Advise patients to not drive or operate machinery if vision is not clear (e.g., blurred vision). In addition, patients may experience temporary dim or dark vision with miotics, including QLOSI. Advise patients to exercise caution in night driving and other hazardous activities in poor illumination.

5.2 Risk of Retinal Detachment Rare cases of retinal detachment have been reported with miotics when used in susceptible individuals and those with pre-existing retinal disease. Examination of the retina is advised in all patients prior to the initiation of therapy. Advise patients to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss.

5.3 Iritis QLOSI is not recommended to be used when iritis is present because adhesions (synechiae) may form between the iris and the lens.

5.4 Contact Lens Wear Contact lens wearers should be advised to remove their lenses prior to the instillation of QLOSI and to wait 10 minutes after dosing before reinserting their contact lenses.

5.5 Potential for Eye Injury or Contamination To prevent eye injury or contamination, avoid touching the tip of the single-patient-use vial to the eye or to any other surface.

Most common adverse reactions (5% to 8%) are instillation site pain and headaches. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orasis Pharmaceuticals Inc. at 1-866-ORASIS1 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. QLOSI was evaluated in 309 patients with presbyopia in two randomized, double-masked, vehicle-controlled studies (NEAR-1 and NEAR-2) of 15 days duration. The most commonly reported treatment-related adverse events in 5-8% of patients were instillation site pain, and headache. Ocular adverse reaction reported in 2-5% of patients was blurred vision. The majority of the adverse events were mild, transient and self-resolving.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of QLOSI administration in pregnant women to inform a drug associated risk. Oral administration of pilocarpine to pregnant rats throughout organogenesis and lactation did not produce adverse effects at clinically relevant doses. Data Animal Data In embryofetal development studies, oral administration of pilocarpine to pregnant rats throughout organogenesis produced maternal toxicity, skeletal anomalies and reduction in fetal body weight at 90 mg/kg/day (approximately 1200-fold higher than the maximum recommended human ophthalmic dose [MRHOD] of 0.012mg/kg/day, on a mg/m 2 basis). In peri-/postnatal study in rats, oral administration of pilocarpine during late gestation through lactation increased stillbirths at a dose of 36 mg/kg/day (approximately 475-fold higher than the MRHOD of 0.012mg/kg/day, on a mg/m 2 basis). Decreased neonatal survival and reduced mean body weight of pups were observed at ≥18mg/kg/day (approximately 240-fold higher than the MRHOD of 0.012mg/kg/day, on a mg/m 2 basis).

8.2 Lactation Risk Summary There are no data on the presence of pilocarpine in human milk, the effects on breastfed infants, or the effects on milk production to inform the risk of QLOSI to an infant during lactation. Pilocarpine and/or its metabolites are excreted in the milk of lactating rats following single oral administration. Systemic levels of pilocarpine following topical ocular administration are low [see Clinical Pharmacology (12.3) ], and it is not known whether measurable levels of pilocarpine would be present in maternal milk following ocular administration of QLOSI. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for QLOSI and any potential adverse effects on the breastfed child from QLOSI. Data Animal Data Following a single oral administration of 14 C-pilocarpine to lactating rats, the radioactivity concentrations in milk were similar to those in plasma. Peak concentrations were observed at 0.5 h, with both milk and plasma levels declining at similar rates, but still detectable at 24 h.

8.4 Pediatric Use Presbyopia is an age-related condition which does not appear in the pediatric population.

8.5 Geriatric Use Clinical studies of QLOSI did not include subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with ophthalmic pilocarpine solutions have not identified overall differences in safety between elderly and younger patients. Safety and effectiveness have not been established in patients over the age of 65.

Pilocarpine hydrochloride is a cholinergic muscarinic agonist which activates muscarinic receptors located at smooth muscles such as the iris sphincter muscle and ciliary muscle. QLOSI contracts the iris sphincter muscle, constricting the pupil to enhance the depth of focus and improve near visual acuity while maintaining some pupillary response to light.