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           Very common         Common           Uncommon         Rare              Very rare           Not Organ Class                                                                                                  known (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                               Hypersensitivi                    Anaphylactic System                               ty                                shock disorders
Metabolism                           Dehydration

 and nutrition disorders
Nervous                       Taste disorder    Cerebrovascul system                        Peripheral        ar accident disorders                     motor             Ischaemic neuropathy        stroke
Peripheral        Haemorrhage sensory           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 supraventricul ar
Vascular                                        Peripheral disorders                                       ischaemiac
Respiratory,                                    Pulmonary thoracic and                                    embolism mediastinal                                     Interstitial disorders                                       pneumonitisbd
Gastrointestin   Stomatitis   Dyspepsia         Rectal al disorders     Anorexia     Constipation      haemorrhage
Vomiting     Abdominal         Gastrointestina
Diarrhoea    pain              l haemorrhage
Nausea                         Intestinal perforation
Oesophagitis
Colitis e
Hepatobiliary                 Aalanine                            Hepatitis disorders                     aminotransfera se increased
Aspartate aminotransfera se increased


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 epidermolysis bullosa
Erythematous oedemaf
Pseudocellulitis
Dermatitis
Eczema
Prurigo
Renal and         Creatinine    Renal failure                                                     Nephro urinary           clearance     Glomerular                                                        genic disorders         decreased     filtration rate                                                   diabete Blood         decreased                                                         s creatinine                                                                      insipid increasede                                                                      us 
Renal tubular necrosi s
General           Fatigue       Pyrexia disorders and                   Pain administration                  Oedema site conditions                 Chest pain
Mucosal inflammation

Investigations                  Gamma- glutamyltransf erase 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 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