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 (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 Organ     Very          Common            Uncommon           Rare           Very rare      Not known Class            common
(MedDRA)
Infections and   Infectiona    Sepsisb                                             Dermohypoder infestations     Pharyngitis                                                       -mitis Blood and        Neutropenia   Febrile          Pancytopenia        Autoimmune lymphatic        Leukopenia    neutropenia                          haemolytic system           Haemoglobin   Platelet count                       anaemia disorders        decreased     decreased
Immune                         Hypersensitivity                     Anaphylactic System                                                              shock disorders
Metabolism                     Dehydration and nutrition disorders
Nervous                        Taste disorder    Cerebrovascular system                         Peripheral        accident disorders                      motor             Ischaemic stroke neuropathy        Haemorrhage
Peripheral        intracranial sensory 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 supraventricular

Vascular                                         Peripheral disorders                                        ischaemiac
Respiratory,                                     Pulmonary thoracic and                                     embolism mediastinal                                      Interstitial disorders                                        pneumonitisbd
Gastrointestinal Stomatitis    Dyspepsia         Rectal disorders                      Constipation      haemorrhage
Anorexia      Abdominal pain    Gastrointestinal haemorrhage
Vomiting                        Intestinal perforation
Diarrhoea                       Oesophagitis
Colitise
Nausea
Hepatobiliary                    Aalanine                          Hepatitis disorders                        aminotransferas e increased

Aspartate aminotransfera se increased
Skin and           Rash          Hyperpigment                      Erythema     Stevens- subcutaneous                     ation                                          Johnson tissue disorders   Skin          Pruritus                                       syndromeb exfoliation
Erythema                                       Toxic multiforme                                     epidermal
Alopecia                                       necrolysisb

Urticaria                                      Pemphigoid

Dermatitis bullous
Acquired epidermolysis bullosa

Erythema-tous oedemaf
Pseudocellu- litis Dermatitis

Eczema
Prurigo
Renal and          Creatinine    Renal failure                                                     Nephrogenic urinary            clearance     Glomerular                                                        diabetes disorders          decreased     filtration rate                                                   insipidus decreased
Blood                                                                           Renal tubular creatinine                                                                      necrosis increasede
General            Fatigue       Pyrexia disorders and administration                   Pain site conditions
Oedema

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