Mercaptamine Other names: Cysteamine

No data on the effect of mercaptamine on human fertility are available. Studies in animals have shown a reduction on fertility.

Experience has occasionally shown that some forms of cysteamine are less well tolerated (i.e. leading to more adverse events) when patients are on dialysis. A closer monitoring of the leucocyte cystine levels is recommended in these patients.

Dose adjustment is not normally required; however, leucocyte cystine levels should be monitored.

The recommended total daily ocular dose of mercaptamine is no more than approximately 0.4% of the highest recommended dose of oral mercaptamine in any age group. Systemic exposure of mercaptamine following ocular administration is therefore lower than following oral administration. Although no effects during pregnancy are anticipated, since systemic exposure to mercaptamine is negligible, precautions should be taken with concomitant treatment with oral mercaptamine.

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

Therefore, mercaptamine 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 mercaptamine.

The recommended total daily ocular dose of cysteamine is no more than approximately 0.4% of the highest recommended dose of oral cysteamine in any age group. Systemic exposure of cysteamine following ocular administration is therefore lower than following oral administration. Although no effects during breast-feeding are anticipated, since systemic exposure to cysteamine is negligible, precautions should be taken with concomitant treatment with oral cysteamine.

Mercaptamine excretion in human’s milk is unknown. However, due to the results of animal studies in breast-feeding mothers and neonates, breast-feeding is contraindicated in women taking mercaptamine.

Fertility

No data on the effect of mercaptamine on human fertility are available. Studies in animals have shown a reduction on fertility.

Ocular administration

Mercaptamine may have a minor influence on the ability to drive and use machines.

Temporary (in average less than 1 minute) blurred vision or other visual disturbances may affect the ability to drive or use machines.

If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.

Oral administration

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

Mercaptamine 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.

Ocular administration

Summary of the safety profile

The most common adverse reactions are eye pain, ocular hyperaemia, eye pruritus, lacrimation increased, blurred vision or eye irritation. The majority of these adverse reactions are transient and most are mild or moderate.

Tabulated list of adverse reactions

The following adverse reactions were reported during clinical trials and the French NPU programme with mercaptamine. Reported adverse reactions are listed below, by system organ class and by frequency (by patient).

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Paediatric population

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.

Oral administration

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 mercaptamine 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 mercaptamine preparations (mercaptamine chlorhydrate or cystamine or mercaptamine 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 mercaptamine dose reduction.

Mercaptamine mechanism of action by interfering with the cross-linking of collagen fibers has been postulated.