Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of safety profile
Abrupt discontinuation of the administration of inhaled nitric oxide may cause rebound reaction; decrease in oxygenation and increase in central pressure and subsequent decrease in systemic blood pressure. Rebound reaction is the most commonly adverse reaction in association with the clinical use of Mixture NO 800 ppm in Nitrogen. The rebound may be seen early as well as late during therapy.
In one clinical study (NINOS), treatment groups were similar with respect to the incidence and severity of intracranial haemorrhage, Grade IV haemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary haemorrhage, or gastrointestinal haemorrhage.
Tabulated list of adverse reactions
The table below presents adverse reactions (ADRs) that have been reported with the use of Mixture NO 800 ppm in Nitrogen from either the CINRGI trial of 212 neonates or post marketing experience in neonates (<1 months of age). The displayed frequency categories use the following convention: 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).
System organ      Very common          Common           uncommo      Rare        Very rare     Not known class                                                   n
Blood and         Thrombocytopenia                      Methaemo          -           - a lymphatic                                               globi system                                                  naemiaa disorders
Cardiac                    -                                 -            -           -        Bradycardiab disorders                                                                                      (following abrupt discontinuati on of therapy)
Vascular                   -           Hypotensiona,         -           -            - bd disorders                                ,
Respiratory,               -           Atelectasisa          -           -            -        Hypoxiab,d thoracic and                                                                                   Dyspnoeac mediastinal                                                                                    Chest disorders                                                                                      Discomfortc Dry throatc
Nervous                       -                              -            -            -       Headachec system                                                                                         Dizzinessc disorders a: Identified from the clinical trial b: Identified from Post-Marketing experience c: Identified from Post-Marketing experience, experienced by healthcare personnel following accidental exposure d: Post Marketing Safety Surveillance (PMSS) data, effects associated with acute withdrawal of the medicinal product, and /or delivery system failures. Rapid rebound reactions such as intensified pulmonary vasoconstriction and hypoxia after sudden withdrawal of inhaled nitric oxide therapy has been described, precipitating cardiovascular collapse.

Description of selected adverse reactions
Inhaled nitric oxide therapy may cause an increase in methaemoglobin.
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