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
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