英文药名：Cystadrops（mercaptamine eye drops solution）
Frequency, type and severity of adverse reactions in children are the same as in adults.
69 paediatric patients were followed through clinical trials and the French NPU programme. 19 patients were under 6 years old, 21 between 6 and 12 years old and 29 between 12 and 18 years old.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
Yellow Card Scheme
Health Products Regulatory Authority
Tel: +353 1 6764971
Fax: +353 1 6762517
Overdose is unlikely to occur with ocular administration.
In case of accidental ingestion, monitoring and symptomatic management of the patient should be implemented.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Ophtalmologicals, other ophtalmologicals, ATC code: S01XA21.
Mechanism of action
Cysteamine reduces corneal cystine crystal accumulation acting as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides.
Clinical efficacy and safety
Two clinical trials were performed with Cystadrops: a single arm clinical trial on 8 children and adults (OCT-1 study) and a randomised, multi-centre, open label, active controlled phase III clinical trial (CHOC study) conducted on 32 patients.
This study assessed the safety and efficacy of Cystadrops during 5 years. Dose adaptation was performed following ocular examination. None of the patients discontinued treatment over the 5 year follow-up.
The efficacy was assessed with In-Vivo Confocal Microscopy total score (IVCM score) by quantifying the cystine crystals in the 7 layers of the cornea. After 30 days of treatment and at a median frequency of 4 instillations per day, an average 30% decrease in the IVCM total score was observed. A mean decrease in corneal cystine crystal deposits of 30%, in comparison with baseline, was maintained over time with a median dosing regimen of 3 drops/eye/day (range 1-3 drops) for 7 of the 8 patients. Photophobia tended to improve over time.
This study was a randomised, controlled trial to assess the efficacy and the safety profile of Cystadrops following a period of 90 days of treatment at a dose regimen of 4 drops/eye/day. The IVCM total score was the primary efficacy endpoint. 15 patients were exposed to Cystadrops. The mean IVCM total score was calculated for 11 patients. A trend towards a lower IVCM total score in Cystadrops arm was observed at day 30. The mean decrease by 40% in the Cystadrops arm was confirmed at day 90. Superiority of Cystadrops was demonstrated compared to the control arm (cysteamine hydrochloride 0.10%) p<0.001 95% CI (2.11; 5.58). Superiority of Cystadrops was also demonstrated for photophobia rated by the investigator compared to the control arm (cysteamine hydrochloride 0.10%) p< 0.048 95% CI (0.23; 1.14).
Clinical data on safety and efficacy were collected during the 2 clinical trials (OCT-1 and CHOC studies). In total 15 paediatric patients were exposed to Cystadrops whereof 3 subjects (including one 2 year and one 3 year old subject) being less than 6 years of age. The efficacy and safety results are similar in both paediatric and adult populations.
The European Medicines Agency has deferred the obligation to submit the results of studies with Cystadrops in one or more subsets of the paediatric population in the treatment of corneal cystine crystal deposits in cystinosis patients (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Human pharmacokinetic assessment following ocular administration of Cystadrops was not performed.
Similarly to other topically administered ocular products, systemic absorption is likely to occur.
However it should be considered that the recommended daily dose of cysteamine applied as eye drops is no more than approximately 0.4% of the highest recommended daily oral dose of cysteamine in any age group.
5.3 Preclinical safety data
Systemic exposure following ocular administration is anticipated to be low. When there is concomitant use of ocular and oral treatment with cysteamine the contribution to any systemic risk from ocular administration is considered negligible.
Preclinical data on oral cysteamine:
Genotoxicity studies have been performed: induction of chromosome aberrations in cultured eukaryotic cell lines has been reported and specific studies with cysteamine did not show any mutagenic effects in the Ames test or any clastogenic effect in the mouse micronucleus test.
Reproduction studies showed embryofoetotoxic effects (resorptions and post-implantation losses) in rats at the 100 mg/kg/day dose level and in rabbits receiving cysteamine 50 mg/kg/day. Teratogenic effects have been described in rats when cysteamine is administered over the period of organogenesis at a dose of 100 mg/kg/day.
This is equivalent to 0.6 g/m2/day in the rat, which is less than half the recommended clinical maintenance dose of cysteamine, i.e. 1.30 g/m2/day. A reduction of fertility was observed in rats at 375 mg/kg/day, a dose at which body weight gain was retarded. At this dose, weight gain and survival of the offspring during lactation was also reduced. High doses of cysteamine impair the ability of lactating mothers to feed their pups. Single doses of the drug inhibit prolactin secretion in animals.
Administration of cysteamine in neonate rats induced cataracts.
High doses of cysteamine, either by oral or parenteral routes, produce duodenal ulcers in rats and mice but not in monkeys. Experimental administration of the drug causes depletion of somatostatin in several animal species. The consequence of this for the clinical use of the drug is unknown.
No carcinogenic studies have been conducted with cysteamine.
6. Pharmaceutical particulars
6.1 List of excipients
Citric acid monohydrate
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for injections
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
After first opening: 7 days. Store below 25°C. Do not refrigerate. Keep the dropper bottle tightly closed in the outer carton in order to protect from light.
6.4 Special precautions for storage
Before first opening:
Store in a refrigerator (2°C - 8°C).
Keep the vial in the outer carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see section 6.3.
6.5 Nature and contents of container
5 mL solution in a 10 mL amber glass vial closed by a bromobutyl stopper and sealed with an aluminium tear-off cap. A PVC dropper applicator with HDPE closure is packed separately and included in each carton box.
Each carton box contains 1 vial and 1 dropper applicator.
6.6 Special precautions for disposal and other handling
The patient should be advised to follow the instructions below for opening of the vial and attachement of the dropper applicator:
• Wash your hands carefully in order to avoid microbiological contamination of the content in the vial.
• Remove the green protective cap (picture 1).
• Remove the metal seal (picture 2).
• Remove the grey stopper (picture 3) from the vial.
• Do not touch the opening of the vial after removing the grey stopper.
Cystadrops 3.8mg/ml eye drops（mercaptamine 巯乙胺眼用溶液）
简介：英文药名：Cystadrops（mercaptamine eye drops solution） 中文药名：巯乙胺眼用溶液 生产厂家：法国：Orphan Europe药品介绍新型凝胶药Cystadrops，每日4次滴眼，应用数周后眼部症状即可明显改善， ...