Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The safety profile of aprepitant was evaluated in approximately 6,500 adults in more than 50 studies.
The most common adverse reactions reported at a greater incidence in adults treated with the aprepitant regimen than with standard therapy in patients receiving Highly Emetogenic Chemotherapy (HEC) were: hiccups (4.6 % versus 2.9 %), alanine aminotransferase (ALT) increased (2.8 % versus 1.1 %), dyspepsia (2.6 % versus 2.0 %), constipation (2.4 % versus 2.0 %), headache (2.0 % versus 1.8 %), and decreased appetite (2.0 % versus 0.5 %). The most common adverse reaction reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving Moderately Emetogenic Chemotherapy (MEC) was fatigue (1.4 % versus 0.9 %).

Tabulated list of adverse reactions
The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a greater incidence with aprepitant than with standard therapy or in postmarketing use: 
Frequencies are defined as: 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) and very rare (<1/10,000), not known (cannot be estimated from the available data).

System organ class                 Adverse reaction                                     Frequency Infection and infestations         candidiasis, staphylococcal infection                   rare Blood and lymphatic system         febrile neutropenia, anaemia                         uncommon disorders
Immune system disorders            hypersensitivity reactions including                 not known anaphylactic reactions
Metabolism and nutrition           decreased appetite                                    common disorders                          polydipsia                                              rare Psychiatric disorders              anxiety                                              uncommon disorientation, euphoric mood                           rare
Nervous system disorders           headache                                              common dizziness, somnolence                                uncommon cognitive disorder, lethargy, dysgeusia                  rare
Eye disorders                      conjunctivitis                                          rare Ear and labyrinth disorders        tinnitus                                                rare Cardiac disorders                  palpitations                                         uncommon bradycardia, cardiovascular disorder                     rare
Vascular disorders                 hot flush                                            uncommon 

Respiratory, thoracic and          hiccups                                               common mediastinal disorders
 oropharyngeal pain, sneezing, cough,                     rare postnasal drip, throat irritation


System organ class                   Adverse reaction                                         Frequency Gastrointestinal disorders           constipation, dyspepsia                                   common 
 eructation, nausea*, vomiting*,                          uncommon gastroesophageal reflux disease, abdominal pain, dry mouth, flatulence duodenal ulcer perforation, stomatitis,                      rare abdominal distension, faeces hard, neutropenic colitis
Skin and subcutaneous tissue         rash, acne                                               uncommon disorders                            photosensitivity reaction, hyperhidrosis,                   rare seborrhoea, skin lesion, rash pruritic, Stevens-
Johnson syndrome/toxic epidermal necrolysis pruritus, urticaria                                      not known
Musculoskeletal and connective       muscular weakness, muscle spasms                            rare tissue disorders
Renal and urinary disorders          dysuria                                                  uncommon pollakiuria                                                 rare
General disorders and                fatigue                                                   common administration site conditions
 asthaenia, malaise                                       uncommon oedema, chest discomfort, gait disturbance                   rare
Investigations                       ALT increased                                             common AST increased, blood alkaline phosphatase                uncommon increased red blood cells urine positive, blood sodium                 rare decreased, weight decreased, neutrophil count decreased, glucose urine present, urine output increased                                                             " *Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were reported as adverse reactions only thereafter.

Description of selected adverse reactions
The adverse reactions profiles in adults in the Multiple-Cycle extension of HEC and MEC studies for up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.

In an additional active-controlled clinical study in 1,169 adult patients receiving aprepitant and HEC, the adverse reactions profile was generally similar to that seen in the other HEC studies with aprepitant.

Non-CINV studies
Additional adverse reactions were observed in adult patients treated with a single 40 mg dose of aprepitant for postoperative nausea and vomiting (PONV) with a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.
*Reported in patients taking a higher dose of aprepitant.

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/.