Adverse reactions : תופעות לוואי

4.8   Undesirable effects

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 
Investigations                                Common: Liver function tests abnormal Blood and lymphatic system disorders          Uncommon: Leukopenia
Nervous system disorders                      Common: Headache, encephalopathy Uncommon: Somnolence, convulsions
Gastrointestinal disorders                    Very common: Vomiting, nausea, diarrhoea Common: Abdominal pain, breath odour, dyspepsia,
gastroenteritis
Uncommon: Gastrointestinal ulcer
Renal and urinary disorders                   Uncommon: Nephrotic syndrome Skin and subcutaneous tissue disorders        Common: Skin odour abnormal, rash Uncommon: Hair colour changes, skin striae, skin fragility (molluscoid pseudotumor on elbows)
Musculoskeletal and connective tissue         Uncommon: Joint hyperextension, leg pain, genu disorders                                     valgum, osteopenia, compression fracture, scoliosis.
Metabolism and nutrition disorders            Very common: Anorexia

General disorders and administration site     Very common: Lethargy, pyrexia conditions                                    Common: Asthenia
Immune system disorders                       Uncommon: Anaphylactic reaction Psychiatric disorders                         Uncommon: Nervousness, hallucination 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 the 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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.h ealth.gov.il ).