Cysteamine Ophthalmic Solution

CYSTARAN is a sterile ophthalmic solution containing 6.5 mg/mL of cysteamine hydrochloride, equivalent to 4.4 mg/mL of cysteamine (0.44%) as the active ingredient. Cysteamine is a cystine-depleting agent which lowers the cystine content of cells in patients with cystinosis.

Molecular Formula: C2H7NS HCl
Molecular Weight: 113.61

Each milliliter of CYSTARAN contains: Active: cysteamine 4.4 mg (equivalent to cysteamine hydrochloride 6.5 mg); Preservative: benzalkonium chloride 0.1 mg; Inactive Ingredients: sodium chloride, hydrochloric acid and/or sodium hydroxide (to adjust pH to 4.1-4.5), and purified water.

Dosage Forms And Strengths

Sterile ophthalmic solution containing 6.5 mg/mL of cysteamine hydrochloride equivalent to 4.4 mg/mL of cysteamine (0.44%).

Storage And Handling

CYSTARAN (cysteamine ophthalmic solution) 0.44% is supplied in a 15 mL, opaque, white, low-density polyethylene (LDPE) bottle with a 15 mm white, LDPE controlled dropper tip and closed with a white, polypropylene screw cap.

Store in freezer at -25°C to -15°C (-13°F to 5°F). Thaw for approximately 24 hours before use. Store thawed bottle at 2°C to 25°C (36°F to 77°F) for up to 1 week. Do not refreeze. Discard after 1 week of use.

NDC 54482-020-01

Manufactured by: Hi-Tech Pharmacal, Co., Inc., Amityville, NY 11701 for sigma-tau, Pharmaceuticals, Inc, Gaithersburg, MD 20878. Revised: 10/2012

Clinical Studies 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.

The safety data described below reflect exposure in controlled clinical trials of six months to 19 years duration in approximately 300 patients.

The most frequently reported ocular adverse reactions occurring in ≥ 10% of patients were sensitivity to light, redness, and eye pain/irritation, headache and visual field defects.

Mechanism of Action

Cysteamine acts as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides and reduces corneal cystine crystal accumulation.

Pharmacokinetics

The peak plasma concentration of cysteamine following ocular administration of cysteamine ophthalmic solution in humans is unknown, but it is expected to be substantially less than the peak plasma concentration following oral administration of cysteamine bitartrate.

Clinical Studies

Clinical efficacy was evaluated in controlled clinical trials in approximately 300 patients. The primary efficacy end point was the response rate of eyes that had a reduction of at least 1 unit in the photo-rated Corneal Cystine Crystal Score (CCCS) at some time point during the study when baseline CCCS ≥ 1, or a lack of an increase of more than 1 unit in CCCS throughout the study when baseline CCCS < 1.

Study 1 combined the data from three smaller studies. For eyes with a lower baseline of CCCS < 1, the response rate was 13% (4/30) [95% CI: (4, 32)]. For eyes with a higher baseline of CCCS ≥ 1, the response rate was 32% (94/291) [95% CI: (27, 38)].

Study 2 evaluated ocular cystinosis patients who had a baseline of CCCS ≥ 1. The response rate was 67% (10/15) [95% CI: (38, 88)].

Study 3 also evaluated ocular cystinosis patients; for eyes with a baseline of CCCS ≥ 1, the response rate was 33% (3/9) [95% CI: (8, 70)].

Corneal crystals accumulate if CYSTARAN is discontinued.