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: ≥ 1/1,000 to < 1/100; rare: ≥ 1/10,000 to < 1/1,000; very rare: < 1/10,000) and not known (cannot be estimated from the available data).
Table 4. Frequencies of all grades adverse drug events regardless of causality from the pivotal registration studies: JMEI (ALIMTA vs Docetaxel), JMDB (ALIMTA and Cisplatin versus GEMZAR and Cisplatin, JMCH (ALIMTA plus Cisplatin versus Cisplatin), JMEN and PARAMOUNT (Pemetrexed plus Best Supportive Care versus Placebo plus Best Supportive Care) and from post-marketing period.
System Organ Class Very common Common                                    Uncommon           Rare              Very rare              Not known (MedDRA)
Infections and              Infection a
Sepsis  b
Dermo-hypodermitis infestations                Pharyngitis
Blood and lymphatic         Neutropenia      Febrile neutropenia         Pancytopenia       Autoimmune system disorders            Leukopenia       Platelet count                                 haemolytic Haemoglobin decreased                                           anaemia decreased
Immune System                                Hypersensitivity                               Anaphylactic disorders                                                                                   shock Metabolism and                               Dehydration nutrition disorders
Nervous system                               Taste disorder              Cerebrovascular disorders                                    Peripheral motor            accident neuropathy                  Ischaemic stroke
Peripheral sensory          Haemorrhage neuropathy                  intracranial
Dizziness
Eye disorders                                Conjunctivitis
Dry eye
Lacrimation increased
Keratoconjunctivitis sicca
Eyelid oedema
Ocular surface disease
Cardiac disorders                            Cardiac failure             Angina Arrhythmia                  Myocardial infarction
Coronary artery disease
Arrhythmia supraventricular
Vascular disorders                                                       Peripheral ischaemiac
Respiratory, thoracic                                                    Pulmonary and mediastinal                                                          embolism disorders                                                                Interstitial pneumonitisbd
Gastrointestinal            Stomatitis       Dyspepsia                   Rectal disorders                   Anorexia         Constipation                haemorrhage Vomiting         Abdominal pain              Gastrointestinal
Diarrhoea                                    haemorrhage
Nausea                                       Intestinal perforation
Oesophagitis
Colitise
Hepatobiliary disorders                      Aalanine                                       Hepatitis aminotransferase increased
Aspartate aminotransferase increased
Skin and subcutaneous Rash                   Hyperpigmentation                              Erythema          Stevens-Johnson tissue disorders            Skin exfoliation Pruritus                                                         syndromeb Erythema multiforme                                              Toxic epidermal Alopecia                                                         necrolysisb Urticaria                                                        Pemphigoid Dermatitis bullous
Acquired epidermolysis bullosa
Erythematous oedemaf
Pseudocellulitis
Dermatitis
Eczema
Prurigo
Renal and urinary           Creatinine       Renal failure                                                                           Nephrogenic disorders                   clearance        Glomerular filtration                                                                   diabetes decreased        rate decreased                                                                          insipidus Blood creatinine                                                                                         Renal tubular increasede                                                                                               necrosis General disorders and Fatigue                Pyrexia administration site                          Pain conditions                                   Oedema
Chest pain
Mucosal inflammation
Investigations                               Gamma- glutamyltransferase increased
Injury, poisoning                                                        Radiation          Recall and procedural                                                           oesophagitis       phenomenon complications                                                            Radiation 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 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/