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 <1/1000; 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 gemcitabine 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 Organ Very common Common                  Uncommon       Rare            Very rare      Not 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                          Hyper-                          Anaphylactic System                          sensitivity                     shock disorders

Metabolism                      Dehydration and nutrition disorders

Nervous                         Taste disorder   Cerebro- system                          Peripheral       vascular disorders                       motor            accident neuropathy       Ischaemic
Peripheral       stroke sensory          Haemorrhage neuropathy       intracranial
Dizziness
Eye disorders                   Conjunctivitis
Dry eye
Lacrimation increased
Kerato- conjunctivitis sicca
Eyelid oedema
Ocular surface disease


System Organ Very common Common                  Uncommon        Rare           Very rare      Not known Class
(MedDRA)

Cardiac                         Cardiac failure Angina disorders                       Arrhythmia      Myocardial infarction
Coronary artery disease
Arrhythmia supra- ventricular

Vascular                                         Peripheral disorders                                        ischaemiac
Respiratory,                                     Pulmonary thoracic and                                     embolism mediastinal                                      Interstitial disorders                                        pneumonitisbd

Gastrointestinal Stomatitis     Dyspepsia        Rectal disorders        Anorexia       Constipation     haemorrhage
Vomiting       Abdominal        Gastro-
Diarrhea       pain             intestinal
Nausea                          haemorrhage
Intestinal perforation
Oesophagitis
Colitise

Hepatobiliary                   Alanine amino-                   Hepatitis disorders                       transferase increased
Aspartate amino- transferase increased


System Organ Very common Common                   Uncommon       Rare           Very rare       Not known Class
(MedDRA)

Skin and         Rash           Hyper-                           Erythema       Stevens- subcutaneous Skin               pigmentation                                    Johnson tissue disorders exfoliation    Pruritus                                        syndromeb Erythema                                        Toxic multiforme                                      epidermal
Alopecia                                        necrolysisb
Urticaria                                       Pemphigoid
Dermatitis bullous
Acquired epidermolysis bullosa
Erythematous oedemaf
Pseudocell ulitis
Dermatitis
Eczema
Prurigo

Renal and         Creatinine    Renal failure                                                   Nephrogenic urinary           clearance     Glomerular                                                      diabetes disorders         decreased     filtration rate                                                 insipidus Blood         decreased                                                       Renal tubular creatinine                                                                    necrosis increasede

General           Fatigue       Pyrexia disorders and                   Pain administration                  Oedema site conditions                 Chest pain
Mucosal inflammation

Investigations                  Gamma- glutamyl- transferase increased
Injury,                                           Radiation      Recall poisoning and                                     oesophagitis   phenomenon procedural                                        Radiation complications                                     pneumonitis a with and without neutropenia b in some cases fatal c sometimes leading to extremity necrosis
 d with respiratory insufficiency
 l i       bi i       ih i l i

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.
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