Adverse reactions : תופעות לוואי

4.8      Undesirable effects

Summary of the safety profile
The most commonly reported undesirable effects related to pemetrexed, whether used as monotherapy or in combination, are bone marrow suppression manifested as anaemia, neutropenia, leukopenia, thrombocytopenia and gastrointestinal toxicities, manifested as anorexia, nausea, vomiting, diarrhoea, constipation, pharyngitis, mucositis, and stomatitis.
Other undesirable effects include renal toxicities, increased aminotransferases, alopecia, fatigue, dehydration, rash, infection/sepsis and neuropathy. Rarely seen events include Stevens-Johnson syndrome and toxic epidermal necrolysis.

Tabulated list of adverse reactions

The table 4 lists the adverse drug events regardless of causality associated with pemetrexed used either as a monotherapy treatment or in combination with cisplatin from the pivotal registration studies (JMCH, JMEI, JMBD, JMEN and PARAMOUNT) and from the post marketing period.

ADRs are listed by MedDRA body system organ class. The following convention has been used for classification of frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000) and not known (cannot be estimated from available data).

Table 4 - Frequencies of all grades adverse drug events regardless of causality from the pivotal registration studies: JMEI (pemetrexed vs docetaxel), JMDB (pemetrexed and cisplatin versus GEMZAR and cisplatin, JMCH (pemetrexed plus cisplatin versus cisplatin), JMEN and PARAMOUNT (pemetrexed plus Best Supportive Care versus Placebo plus Best Supportive Care) and from post-marketing period.

System            Very         Common          Uncommo          Rare      Very rare       Not Organ           common                            n                                      known Class
(MedDRA)
Infections and   Infectiona    Sepsisb                                      Dermo- infestations     Pharyngitis                                                hypodermitis Blood and        Neutropenia   Febrile           Pancytopenia Autoimmune lymphatic        Leukopenia    neutropenia                    haemolytic system           Haemoglobin   Platelet count                 anaemia disorders        decreased     decreased
Immune                         Hypersensiti-                   Anaphylac- System                         vity                            tic shock disorders


System           Very        Common           Uncommo             Rare     Very rare    Not Organ          common                            n                                     known Class
(MedDRA)
Metabolism                   Dehydration and nutrition disorders
Nervous                      Taste disorder     Cerebrovasc system                       Peripheral         ular accident disorders                    motor              Ischaemic neuropathy         stroke
Peripheral         Haemorrhag sensory            e intracranial neuropathy
Dizziness
Eye disorders                Conjunctivitis
Dry eye
Lacrimation increased
Keratoconjunc tivitis sicca
Eyelid oedema
Ocular surface disease
Cardiac                      Cardiac failure    Angina disorders                    Arrhythmia         Myocardial infarction
Coronary artery disease
Arrhythmia supraventric ular
Vascular                                        Peripheral disorders                                       ischaemiac
Respiratory,                                    Pulmonary thoracic and                                    embolism mediastinal                                     Interstitial disorders                                       pneumonitisb d

Gastrointes-    Stomatitis   Dyspepsia          Rectal tinal           Anorexia     Constipation       haemorrhage disorders       Vomiting     Abdominal          Gastrointesti
Diarrhoea    pain               nal
Nausea                          haemorrhage
Intestinal perforation
Oesophagitis
Colitise
Hepatobiliary                Alanine                             Hepatitis disorders                    aminotransfera se increased
Aspartate aminotransfera se increased



System             Very        Common            Uncommo          Rare    Very rare         Not Organ            common                             n                                      known Class
(MedDRA)
Skin and         Rash          Hyperpigment                      Erythema   Stevens- subcutaneous     Skin          ation                                        Johnson tissue           exfoliation   Pruritus                                     syndromeb disorders                      Erythema                                     Toxic multiforme                                   epidermal
Alopecia                                     necrolysisb
Urticaria                                    Pemphigoid
Dermatitis bullous
Acquired epidermolysi s bullosa
Erythema- tous oedemaf
Pseudocellu- litis
Dermatitis
Eczema
Prurigo
Renal and        Creatinine    Renal failure                                               Nephroge- urinary          clearance     Glomerular                                                  nic diabetes disorders        decreased     filtration rate                                             insipidus Blood         decreased                                                   Renal creatinine                                                                tubular increasede                                                                necrosis General          Fatigue       Pyrexia disorders and                  Pain administratio                  Oedema n site                         Chest pain conditions                     Mucosal inflammation
Investigations                 Gamma- glutamyltransf erase increased
Injury,                                           Radiation      Recall poisoning and                                     oesophagitis   pheno- procedural                                        Radiation      menon complications                                     pneumonitis
 a with and without neutropenia b in some cases fatal c sometimes leading to extremity necrosis d with respiratory insufficiency e seen only in combination with cisplatin f mainly of the lower limbs

Reporting of suspected adverse reactions
Reporting suspected adverse reactions 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 via the following link: https://sideeffects.health.gov.il/