Mesna Other names: Coenzyme M sodium salt

Hypersensitivity reactions to mesna have been reported following administration of mesna as an uroprotectant. These include various skin and subcutaneous tissue symptoms.

In addition, cases of severe bullous and ulcerative skin and mucosal reactions were reported.

In some cases, skin reactions were accompanied by one or more other symptoms, such as fever, cardiovascular, pulmonary symptoms, haematological abnormalities, nausea, vomiting, pain in the extremities, arthralgia, myalgia, malaise and conjunctivitis.

Some reactions have presented as anaphylaxis.

Fever accompanied by, e.g., hypotension but no skin manifestations has also been reported.

Some patients with a history of a reaction have shown positive delayed-type skin test results. However, a negative delayed reaction does not exclude hypersensitivity to mesna. Positive immediate-type skin test reactions have occurred in patients regardless of previous mesna exposure or history of hypersensitivity reactions, and may be related to the concentration of the mesna solution used for testing.

Prescribers should be aware that:

• severe as well as minor reactions were reported with the use of mesna in regimens to treat both severe systemic autoimmune disease and malignancy and that mesna should be suspected in any hypersensitivity reaction,
• these reactions may occur with first exposure or after several months of exposure and in some cases can be life threatening,
• the occurrence and severity of reactions appeared to vary with the dose administered with a tendency to shorter intervals following subsequent exposures,
• hypersensitivity reactions to mesna were interpreted to resemble the clinical picture of sepsis and, in patients with autoimmune disorders, resemble an exacerbation of the underlying disease.

There are no adequate data from the use of mesna in pregnant women. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing mesna.

Pregnancy is contraindication for cytostatic treatment, and consequently mesna is not likely to be used under this circumstance.

Should an individual patient be undergoing oxazaphosphorine therapy during pregnancy then mesna should be administered to this patient.

There are no adequate data from the use of mesna in lactating women. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing mesna.

Lactation is contraindication for cytostatic treatment, and consequently mesna is not likely to be used under this circumstance.

Mothers should not breast-feed whilst being treated with these drugs.

Animal studies have shown no evidence of embryotoxic or teratogenic effects of mesna.

Patients undergoing treatment with mesna may experience undesirable effects (including, e.g., syncope, light-headedness, lethargy/drowsiness, dizziness, and blurred vision) which could affect the ability to drive or use machines. The decision to drive or operate machinery should be made on an individual basis.

The most frequently occurring adverse reactions (>10%) associated with use of mesna are: headache, abdominal pain/colic, light headedness, lethargy/drowsiness, pyrexia, rash, diarrhoea, nausea, flushing, and influenza-like illness.

The most severe adverse reactions associated with use of mesna are: bullous skin reactions, anaphylaxis, and drug rash with eosinophilia and systemic symptoms (DRESS).

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

ADR frequency is based upon the following scale: 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), Unknown (adverse reactions reported in the post-marketing experience)

Blood and lymphatic system dirorders

Common: Lymphadenopathy

Immune system disorders

Unknown: Anaphylaxis, Hypersensitivity

Metabolism and nutrition disorders

Common: Decreased appetite, Feeling of dehydration

Psychiatric disorders

Common: Insomnia, Nightmare

Nervous system disorders

Very common: Headache, Light-headedness, Lethargy/Drowsiness

Common: Dizziness, Paresthesia, Hyperesthesia, Syncope, Hypoesthesia, Disturbance in attention

Eye disorders

Common: Conjunctivitis, Photophobia, Vision blurred

Cardiac disorders

Common: Palpitations

Unknown: Tachycardia

Vascular disorders

Very common: Flushing

Unknown: Hypotension

Respiratory, thoracic, and mediastinal disorders

Common: Nasal congestion, Cough, Pleuritic pain, Dry mouth, Bronchospasm, Dyspnea, Laryngeal discomfort, Epistaxis

Unknown: Respiratory distress, Hypoxia

Gastrointestinal disorders

Very common: Abdominal pain/colic, Nausea, Diarrhoea

Common: Mucosal irritation¹, Flatulence, Vomiting, Burning pain (substernal/epigastric), Constipation, Gingival bleeding

Hepatobiliary disorders

Common: Transaminases increased

Skin and subcutaneous tissue disorders

Very common: Rash²

Common: Pruritus, Hyperhidrosis

Unknown: Erythema multiforme, Drug rash³, Ulcerations and/or bullae/blistering⁴, Angioedema, Urticaria, Burning sensation, Erythema

Musculoskeletal and connective tissue disorders

Common: Arthralgia, Back pain, Myalgia, Pain in extremity, Pain in jaw

Renal and urinary disorders

Common: Dysuria

Unknown: Acute renal failure

General disorders and administrative site conditions

Very common: Pyrexia, Influenza-like illness³

Common: Rigors, Fatigue, Chest pain, Malaise

Unknown: Face oedema, Oedema peripheral, Asthenia

Investigations

Unknown: Activated partial thromboplastin time prolonged

¹ Oral, rectal
² Including nonpruritic, pruritic, erythema/erythematous, eczematous, papular, and/or macular rashes.
³ mucocutaneous, mucosal, oral, vulvovaginal, anorectal
⁴ vesicular, exfoliative, maculo-papular, morbilliform

Time to onset and experience with re-exposure

In these studies, some subjects experienced their events on first exposure to mesna and others after the second or third exposure. In general, the complete spectrum of symptoms experienced by a subject developed over a period of several hours.

Some subjects experienced no further reactions after their initial event while others experienced an exacerbation of events upon repeated dosing.

Cutaneous/mucosal reactions

Cutaneous and mucosal reactions were reported to occur after both intravenous and oral mesna. These reactions included rashes, pruritus, flushing, mucosal irritation, pleuritic pain, and conjunctivitis. Approximately one-quarter of subjects with any event experienced cutaneous/mucosal reactions in conjunction with other adverse symptoms, which included, dyspnea, fever, headache, gastrointestinal symptoms, drowsiness, malaise, myalgia, and influenza-like symptoms.

Gastrointestinal reactions

Gastrointestinal reactions reported in healthy subjects included nausea, vomiting, diarrhoea, abdominal pain/colic, epigastric pain/burning, constipation, and flatulence and were reported to occur after intravenous and oral mesna administration.

In-vivo effect on lymphocyte counts

In pharmacokinetics studies in healthy volunteers, administration of single doses of mesna was commonly associated with a rapid (within 24 hours) and in some cases marked decrease in lymphocyte count, which was generally reversible within 1 week of administration. Data from studies with repeated dosing over several days are insufficient to characterize the time course of lymphocyte count changes under such conditions.

In-vivo effect on serum phosphorus levels

In pharmacokinetics studies in healthy volunteers, administration of mesna on single or multiple days was in some cases associated with moderate transient increases in serum phosphorus concentration.

These phenomena should be considered when interpreting laboratory results.