Adverse reactions : תופעות לוואי

4.8 Undesirable Effects
Occurrence and severity of undesirable effects depend on dosage level and frequency of Methotrexat “Ebewe” administration. However, as severe adverse reactions may occur even at lower doses, it is indispensable that the doctor monitors patients regularly at short intervals.
Most undesirable effects are reversible if recognised early. If such adverse reactions occur, dosage should be reduced or therapy be interrupted and appropriate countermeasures should be taken (see section 4.9). Methotrexate therapy should only be resumed with caution, under close assessment of the necessity for treatment and with increased alertness for possible reoccurrence of toxicity.
Frequencies in this table are defined using the following convention: very common (≥ 1/10), common (≥ 1/100 < 1/10), uncommon (≥ 1/1,000 < 1/100), rare (≥ 1/10,000 < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Further details are given following this table.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The following adverse reactions may occur:
After intramuscular methotrexate administration, local adverse reactions (burning sensation) or damage (formation of sterile abscess, destruction of fatty tissue) may occasionally occur at the injection site.
Subcutaneous methotrexate application indicates a good local tolerability. Up to now, only mild skin reactions have been observed, and their number decreases during treatment.
Very common                     Common                          Uncommon                        Rare                                Very rare Infections and                                                                                                                                                     Sepsis, opportunistic infestations*                                                                                                                                                      infections (may be fatal in some cases), infections caused by the cytomegaly virus
Neoplasms benign,                                                                              Individual cases of lymphoma, malignant and unspecified                                                                      which abated in a number (incl. cysts and polyps)                                                                       of cases once methotrexate treatment had been discontinued. In a recent study, it was not possible to establish that methotrexate therapy increases the incidence of lymphomas
Blood and lymphatic                                            Leukocytopenia,                 Pancytopenia,                   Megaloblastic anaemia               Severe courses of bone system disorders*                                              thrombocytopenia, anaemia       agranulocytosis,                                                    marrow depression, aplastic haematopoietic disorders                                            anaemia; Lymphadenopathy,
lymphoproliferative disorders
(partly reversible), eosinophilia and neutropenia
Immune system disorders*                                                                                                                                           Immunosuppression hypogammaglobulinaemia
Metabolism and nutrition disorders
Psychiatric disorders                                                                                                                                              Insomnia.
Nervous system disorders*                                      Headache, fatigue,              Vertigo, confusion,             Severely impaired vision,           Pain, muscular asthenia or drowsiness                      depression, seizures            mood alterations                    paresthesia of the extremities, changes in sense of taste
(metallic taste), meningism
(paralysis, vomiting), acute aseptic meningitis
Eye disorders                                                                                                                  Visual disturbances                 Conjunctivitis, retinopathy Ear and labyrinth disorders
Cardiac disorders                                                                                                              Pericarditis, pericardial effusion, pericardial tamponade
Vascular disorders                                                                                                             Hypotension, thromboembolic events (including arterial and cerebral thrombosis,
thrombophlebitis, deep vein thrombosis, retinal vein thrombosis, pulmonary embolism)
Respiratory, thoracic and                                      Pulmonary complications          Pulmonary fibrosis             Pharyngitis, apnoea, bronchial Pneumocystis carinii mediastinal disorders                                          due to interstitial alveolitis/                                 asthma                         pneumonia, shortness of pneumonitis and related                                                                        breath, chronic obstructive deaths (independent of                                                                         pulmonary disease.
dose and duration of                                                                           Infections including methotrexate treatment).                                                                       pneumonia have also been Typical symptoms may be:                                                                       observed; Pleural effusion general illness; dry, irritating cough; shortness of breath progressing to rest dyspnoea,
chest pain, fever. If such complications are suspected,
methotrexate treatment must be discontinued immediately and infections (including pneumonia) must be excluded
Gastrointestinal disorders*    Loss of appetite, nausea,       Diarrhoea (especially during    Gastrointestinal ulcers and     Enteritis, melaena gingivitis,      Haematemesis, toxic vomiting, abdominal pain,       the first 24–48 hours           bleeding                        malabsorption                       megacolon inflammation and ulcerations    after administration of of the mucous membrane of       methotrexate) mouth and throat (especially during the first 24–48 hours after administration of methotrexate); Stomatitis,
dyspepsia
Hepatobiliary disorders        Increase in liver-related                                       Development of liver            Acute hepatitis and                 Reactivation of chronic enzymes (ALAT, ASAT, alkaline                                   fattening, fibrosis             hepatotoxicity                      hepatitis, acute liver phosphatase and bilirubin)                                      and cirrhosis (occurs                                               degeneration. Furthermore, frequently despite regularly                                        herpes simplex hepatitis and monitored, normal values                                            liver insufficiency have been of liver enzymes); diabetic                                         observed (also see the notes metabolism; drop of serum                                           regarding liver biopsy in albumin                                                             section 4.4) Skin and subcutaneous                                          Exanthema, erythema, itching    Urticaria, photosensibility,    Increased pigmentary changes        Acute paronychia, tissue disorders                                                                               enhanced pigmentation of        of nails, acne, petechiae,          furunculosis, telangiectasia.
the skin, hair loss, increase   ecchymoses, erythema                Furthermore, nocardiosis, of rheumatic nodules, herpes    multiforme, cutaneous               histoplasma and cryptococcus zoster, painful lesions of      erythematous eruptions              mycosis and disseminated psoriatic plaque; severe                                            herpes simplex have been toxic reactions: vasculitis,                                        reported.
herpetiform eruption of                                             Allergic vasculitis, hidradenitis the skin, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome)
Musculoskeletal system,                                                                        Arthralgia, myalgia,            Stress fracture connective tissue and bone                                                                     osteoporosis disorders

Renal and urinary disorders                                                                    Inflammation and ulceration     Renal failure, oliguria, anuria,    Proteinuria of the urinary bladder          azotaemia
(possibly with haematuria),
dysuria
Reproductive system and                                                                        Inflammation and ulceration                                         Loss of libido, impotence, breast disorders                                                                               of the vagina                                                       oligospermia, impaired menstruation, vaginal discharge, infertility
General disorders and                                                                          Severe allergic reactions                                           Fever, impaired wound administration site                                                                            progressing to anaphylactic                                         healing conditions                                                                                     shock Investigations