Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The most frequently occurring adverse reactions (> 10%) associated with use of mesna are headache, infusion site reactions, abdominal pain/colic, light-headedness, lethargy/drowsiness, fever, rash, diarrhea, nausea, flushing, and flu-like illness.

The most severe adverse reactions associated with use of mesna are toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylaxis, and drug rash with eosinophilia and systemic symptoms (DRESS).

Because mesna is used in combination with oxazaphosphorines, it is often difficult to distinguish adverse reactions that may be due to mesna from those caused by concomitantly administered cytotoxic agents.

Adverse reactions are assessed on the basis of the following frequencies: 
Very common:                                Common:
(1/10)                                     (1/100 to < 1/10)
Uncommon:                                   Rare:
(1/1,000 to < 1/100)                       (1/10,000 to < 1/1,000) Very rare:
(<1/10.000)
Not known: cannot be estimated from the available data

The following table lists the reported adverse reactions by MedDRA system organ classes, stating the respective frequencies.

System organ class (SOC)          Adverse reaction                  Frequency Infections and infestations       Pharyngitis                       Very rare Blood and lymphatic               Lymphadenopathy                   Common system disorders                  Pancytopenia
Leukopenia
Lymphopenia                       Not known
Thrombocytopenia
Eosinophilia
Immune system disorders      Anaphylaxis                  Not known
Hypersensitivity reactions
Metabolism and nutrition     Appetite decreased           Common disorders                    Feeling of dehydration
Psychiatric disorders        Insomnia                     Common
Nightmares
Nervous system disorders     Headache
Light-headedness             Very common
Lethargy/drowsiness
Dizziness
Paresthesia
Hyperesthesia                Common
Syncope
Hypoesthesia
Disturbance in attention
Convulsion                   Not known
Eye disorders                Conjunctivitis
Photophobia                  Common
Blurred vision
Periorbital edema            Not known
Cardiac disorders            Palpitations                 Common
Electrocardiogram            Not known abnormalities
Tachycardia
Vascular disorders           Flushing                     Very common Hypotension                  Not known
Hypertension
Respiratory, thoracic and    Nasal congestion mediastinal disorders        Cough
Pleuritic pain
Xerostomia                   Common
Bronchospasm
Dyspnea
Laryngeal discomfort
Epistaxis
Difficulty breathing
Hypoxia
Reduced oxygen saturation    Not known
Tachypnea
Hemoptysis
Gastrointestinal disorders   Abdominal pain/colic
Nausea                       Very common
Diarrhea
Mucosal irritation1
Flatulence
Burning pain                 Common
(substernal/epigastric)
Constipation
Gingival bleeding
Stomatitis                   Not known
Dysgeusia
Hepatobiliary disorders      Transaminases increased      Common
Hepatitis
Gamma glutamyl transferase   Not known
levels increased
Blood alkaline phosphatase levels increased
Skin and subcutaneous          Rash2                           Very common tissue disorders               Pruritus                        Common Hyperhidrosis
Toxic epidermal necrolysis
Stevens-Johnson syndrome
Erythema multiforme
Drug rash3
Ulceration and/or bullae/blistering4              Not known
Angioedema
Rash
Photosensitivity
Urticaria
Burning sensation
Erythema
Musculoskeletal and            Arthralgia connective tissue disorders    Back pain
Myalgia
Pain in the extremities         Common
Jaw pain
Renal and urinary disorders    Dysuria                         Common Acute renal failure             Not known
General disorders and          At the infusion site: administration site            pruritus, rash                  Very common conditions                     Fever
Flu-like illness
At the infusion site:
Pain, erythema, urticaria,
swelling
Rigors                          Common
Fatigue
Chest pain
Malaise
Facial edema,
Peripheral edema
Asthenia                        Not known
At the infusion site: thrombophlebitis, skin irritation
Investigations                 Lab signs of disseminated intravascular coagulation
Prothrombin time prolonged      Not known
Activated partial thromboplastin time prolonged
1
Oral, rectal
2
Including erythema with or without pruritus and erythematous, eczematous, papular and/or macular rashes.
3 with eosinophilia and systemic symptoms
4 mucocutaneous, mucosal, oral, vulvovaginal, anorectal

Onset of symptoms and re-exposure

Adverse reactions may occur after the first exposure to mesna. In some cases, symptoms are not observed until after the second or third exposure. In general, the complete spectrum of symptoms developed over a period of several hours. Following re-exposure, some patients experienced no further reactions while others experienced definite reactions.

Infusion site reactions
In some patients experiencing local cutaneous infusion site reactions after administration of the drug, subsequent exposure resulted in cutaneous reactions at other locations.

Cutaneous/mucosal reactions
Cutaneous and mucosal reactions have been reported to occur after both intravenous and oral administration of mesna. Approximately one-quarter of subjects with any adverse event experienced cutaneous/mucosal reactions in conjunction with other adverse symptoms, including dyspnea, fever, headache, gastrointestinal symptoms, drowsiness, malaise, myalgia and flu-like symptoms.

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 https://sideeffects.health.gov.il