Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile
In general, adverse reactions seen with betaine anhydrous therapy appeared to be not serious and are mainly related to the gastrointestinal system. Gastrointestinal disorders like diarrhoea, glossitis, nausea, stomach discomfort, vomiting and dental disorders may occur uncommonly.
The most commonly reported adverse reaction during treatment is blood methionine increased. Complete recovery was seen after treatment discontinuation (see section 4.4).
Tabulated summary of adverse reactions
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), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.



Metabolism and nutrition disorders               Uncommon: anorexia Psychiatric disorders                            Uncommon: agitation, depression, irritability, personality disorder, sleep disturbed
Nervous system disorders                         Uncommon: brain oedema* Gastrointestinal disorders                       Uncommon: dental disorders, diarrhoea, glossitis, nausea, stomach discomfort,
vomiting
Skin and subcutaneous tissue disorders           Uncommon: hair loss, hives, skin odour abnormal
Renal and urinary disorders                      Uncommon: urinary incontinence Investigations                                   Very common: blood methionine increased* 

Description of selected adverse reactions
*Uncommon cases of severe cerebral oedema and hypermethioninemia were reported within 2 weeks to 6 months of starting betaine anhydrous therapy in patients with CBS deficiency, with complete recovery after treatment discontinuation.
Symptoms of cerebral oedema include morning headaches with vomiting and/or visual changes
High increases in plasma methionine levels in a range from 1,000 to 3,000 μM were noted in these patients. As cerebral oedema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine anhydrous therapy has been postulated as a possible mechanism of action.
For specific recommendations, refer to section 4.4.
Reporting suspected adverse reaction after authorization 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 https://sideeffects.health.gov.il/ or by email (adr@MOH.HEALTH.GOV.IL ).