CYSTAGON Hard capsule Ref.[113968] Active ingredients: Mercaptamine

CYSTAGON therapy must be initiated promptly after confirmation of the diagnosis of nephropathic cystinosis to achieve maximum benefit.

Nephropathic cystinosis must have been diagnosed by both clinical signs and biochemical investigations (leucocyte cystine measurements).

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in children treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m²/day. These skin lesions were associated with vascular proliferation, skin striae and bone lesions.

It is therefore recommended to monitor regularly skin and to consider X-ray examinations of the bone as necessary. Self-examination of the skin by the patient or the parents should also be advised. If any similar skin or bone abnormalities appear, it is recommended to decrease the dose of CYSTAGON. The use of doses higher than 1.95g/m²/day is not recommended (see sections 4.2 and 4.8).

Monitoring of blood cell count is recommended on a regular basis.

Oral cysteamine has not been shown to prevent eye deposition of cystine crystals. Therefore, where cysteamine ophthalmic solution is used for that purpose, its usage should continue.

In contrast to phosphocysteamine, CYSTAGON does not contain phosphate. Most patients will already be receiving phosphate supplements and the dose of these may need to be altered when CYSTAGON is substituted for phosphocysteamine.

Intact CYSTAGON hard capsules should not be administered to children under the age of approximately 6 years due to risk of aspiration (see section 4.2).

Do not swallow the desiccant canister found in the bottle

No interaction studies have been performed.

CYSTAGON can be administered with electrolyte and mineral replacements necessary for management of the Fanconi syndrome as well as vitamin D and thyroid hormones. Indomethacin and CYSTAGON have been used simultaneously in some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used with cysteamine.

Pregnancy

There are no adequate data from the use of cysteamine bitartrate in pregnant women. Studies in animals have shown reproductive toxicity, including teratogenesis (see section 5.3). The potential risk for humans is unknown. The effect on pregnancy of untreated cystinosis is also unknown.

Therefore, CYSTAGON should not be used during pregnancy, particularly during the first trimester, unless clearly necessary.

If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered and the patient must be advised of the possible teratogenic risk of cysteamine.

Breast-feeding

CYSTAGON excretion in human’s milk is unknown. However, due to the results of animal studies in breast-feeding mothers and neonates (see section 5.3), breast-feeding is contraindicated in women taking CYSTAGON.

CYSTAGON has minor or moderate influence on the ability to drive and use machines.

CYSTAGON may cause drowsiness. When starting therapy, patients should not engage in potentially hazardous activities until the effects of the medicinal product on each individual are known.

Approximately 35% of patients can be expected to experience adverse reactions. These mainly involve the gastrointestinal and central nervous systems. When these effects appear at the initiation of cysteamine therapy, temporary suspension and gradual reintroduction of treatment may be effective in improving tolerance.

Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1,000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriouness.

Cases of nephrotic syndrome have been reported within 6 months of starting therapy with progressive recovery after treatment discontinuation. In some cases, histology showed a membranous glomerulonephritis of the renal allograft and hypersensitivity interstitial nephritis.

Cases of Ehlers-Danlos like syndrome and vascular disorders on elbows have been reported in children chronically treated with high doses of different cysteamine preparations (cysteamine chlorhydrate or cystamine or cysteamine bitartrate) mostly above the maximal dose 1.95 g/m²/day.

In some cases, these skin lesions were associated with vascular proliferation, skin striae and bone lesions first seen during an X-ray examination. Bone disorders reported were genu valgum, leg pain and hyperextensive joints, osteopenia, compression fractures, and scoliosis.

In cases where histopathological examination of the skin was performed, the results suggested angioendotheliomatosis.

One patient subsequently died of acute cerebral ischemia with marked vasculopathy.

In some patients, the skin lesions on elbows regressed after CYSTAGON dose reduction.

Cysteamine mechanism of action by interfering with the cross-linking of collagen fibers has been postulated (see section 4.4).

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 the national reporting system listed in Appendix V.

Not applicable.