Drugs List

Therapeutic Indications

Uses

Urothelial toxicity - prophylaxis

Administration

For intravenous injection

Oral administration of the injection:
Add contents of the ampoule to a flavoured soft drink (e.g. orange juice or cola).

Contraindications

None known

Precautions and Warnings

Autoimmune disease
Children under 18 years
Previous pelvic radiotherapy
Restricted sodium intake
Breastfeeding
Pregnancy
Urinary system disorder

Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Counteracts only urotoxic effects of oxazaphosphorines
Maintain hydration and urinary output
Monitor blood counts regularly
Monitor for haematuria and proteinuria
May affect results of some laboratory tests
May affect urine test results
High risk patients: Increase dose, frequency and total number of doses

Urinary output should be maintained at 100 ml per hour, as is required for the oxazaphosphorine treatment.

Compared with intravenous administration, overall availability of mesna in urine after oral administration is approximately 50%. Additionally, the onset of urinary excretion is delayed by about 2 hours and is more prolonged than following intravenous dosing.

Mesna should be suspected in any hypersensitivity reactions experienced throughout therapy. These reactions may occur immediately after the first exposure, or after several months. The hypersensitivity reactions may resemble sepsis or, in patients with autoimmune disease, may appear to be an exacerbation of the underlying disease. Mesna is a thiol compound. This group of compounds show similarities in their reaction profile, including severe skin reactions. It is not clear whether a patient experiencing a reaction to one thiol compound will experience the same reaction with another thiol compound, but such risk should be considered.

If necessary, the dosage interval of mesna can be reduced to less than 4 hours and/or the number of doses increased. This is recommended in patients who have damaged urothelium from previous treatment with oxazaphosphorines or pelvic radiotherapy. This is also the case for other patients who are not adequately protected by the standard dose.

Pregnancy and Lactation

Pregnancy

Use mesna with caution in pregnancy.

Pregnancy is generally a contraindication for cytostatic treatment and consequently, mesna is rarely used in pregnant patients. However, if a patient is pregnant whilst receiving cytostatic treatment, mesna should be administered. The potential risks and benefits should be considered for each patients before prescribing mesna.

It is not known if mesna crosses the placenta. Its low molecular weight (about 164) suggests it could, but the short elimination half life and rapid metabolism may limit any exposure to the embryo or foetus (Briggs, 2015).

Briggs (2015) suggests mesna poses little or no risk to a human foetus but is probably not protective against any oxazaphosphorine-induced birth defects if these chemotherapy agents are used during the first trimester. However, the maternal benefits from the use of mesna to lessen or prevent urothelial toxicity appear to outweigh the unknown foetal risks.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use mesna with caution in breastfeeding.

Breastfeeding is a contraindication for cytostatic treatment and consequently, mesna is rarely used in breastfeeding patients.

It is not known if mesna is excreted into breast milk. Its low molecular weight (about 164) suggests it could, but the short elimination half life and rapid metabolism may limit the amount of drug that appears in milk (Briggs, 2015).

There is limited data on the use of mesna in breastfeeding women, but if a oxazaphosphorine is clearly indicated despite breastfeeding, there are no limitations on the use of mesna to prevent urothelial toxicity.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal failure
Anaphylaxis
Angioedema
Arthralgia
Asthenia
Attention disturbances
Back pain
Blistering
Blurred vision
Bronchospasm
Burning sensation
Chest pain
Colic
Conjunctivitis
Constipation
Cough
Decreased appetite
Depression
Diarrhoea
Dizziness
Drowsiness
Drug rash
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dyspnoea
Dysuria
Epistaxis
Erythema
Erythema multiforme
Facial oedema
Fatigue
Fever
Flatulence
Flushing
Gingival bleeding
Headache
Hyperesthesia
Hyperhidrosis
Hypersensitivity reactions
Hypoesthesia
Hypotension
Hypoxia
Increased partial thromboplastin time
Increases in serum transaminases (transient)
Influenza-like symptoms
Insomnia
Irritability
Jaw pain
Joint pain
Laryngeal discomfort
Lethargy
Light-headedness
Limb pain
Local burning
Lymphadenopathy
Malaise
Mucosal irritation
Myalgia
Nasal congestion
Nausea
Nightmares
Painful extremities
Palpitations
Peripheral oedema
Photophobia
Pleuritic pain
Pruritus
Pyrexia
Rash
Reduced lymphocyte count
Respiratory distress
Retching
Rigors
Skin tingling
Syncope
Tachycardia
Ulceration
Urticaria
Vertigo
Vomiting

Presentation

Mesna containing injection

Drugs List

Therapeutic Indications

Uses

Urothelial toxicity - prophylaxis

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Patients with Renal Impairment

Administration

For intravenous injection

Oral administration of the injection:
Add contents of the ampoule to a flavoured soft drink (e.g. orange juice or cola).

Contraindications

None known

Precautions and Warnings

Autoimmune disease
Children under 18 years
Previous pelvic radiotherapy
Restricted sodium intake
Breastfeeding
Pregnancy
Urinary system disorder

Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Counteracts only urotoxic effects of oxazaphosphorines
Maintain hydration and urinary output
Monitor blood counts regularly
Monitor for haematuria and proteinuria
May affect results of some laboratory tests
May affect urine test results
High risk patients: Increase dose, frequency and total number of doses

Urinary output should be maintained at 100 ml per hour, as is required for the oxazaphosphorine treatment.

Compared with intravenous administration, overall availability of mesna in urine after oral administration is approximately 50%. Additionally, the onset of urinary excretion is delayed by about 2 hours and is more prolonged than following intravenous dosing.

Mesna should be suspected in any hypersensitivity reactions experienced throughout therapy. These reactions may occur immediately after the first exposure, or after several months. The hypersensitivity reactions may resemble sepsis or, in patients with autoimmune disease, may appear to be an exacerbation of the underlying disease. Mesna is a thiol compound. This group of compounds show similarities in their reaction profile, including severe skin reactions. It is not clear whether a patient experiencing a reaction to one thiol compound will experience the same reaction with another thiol compound, but such risk should be considered.

If necessary, the dosage interval of mesna can be reduced to less than 4 hours and/or the number of doses increased. This is recommended in patients who have damaged urothelium from previous treatment with oxazaphosphorines or pelvic radiotherapy. This is also the case for other patients who are not adequately protected by the standard dose.

Pregnancy and Lactation

Pregnancy

Use mesna with caution in pregnancy.

Pregnancy is generally a contraindication for cytostatic treatment and consequently, mesna is rarely used in pregnant patients. However, if a patient is pregnant whilst receiving cytostatic treatment, mesna should be administered. The potential risks and benefits should be considered for each patients before prescribing mesna.

It is not known if mesna crosses the placenta. Its low molecular weight (about 164) suggests it could, but the short elimination half life and rapid metabolism may limit any exposure to the embryo or foetus (Briggs, 2015).

Briggs (2015) suggests mesna poses little or no risk to a human foetus but is probably not protective against any oxazaphosphorine-induced birth defects if these chemotherapy agents are used during the first trimester. However, the maternal benefits from the use of mesna to lessen or prevent urothelial toxicity appear to outweigh the unknown foetal risks.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use mesna with caution in breastfeeding.

Breastfeeding is a contraindication for cytostatic treatment and consequently, mesna is rarely used in breastfeeding patients.

It is not known if mesna is excreted into breast milk. Its low molecular weight (about 164) suggests it could, but the short elimination half life and rapid metabolism may limit the amount of drug that appears in milk (Briggs, 2015).

There is limited data on the use of mesna in breastfeeding women, but if a oxazaphosphorine is clearly indicated despite breastfeeding, there are no limitations on the use of mesna to prevent urothelial toxicity.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal failure
Anaphylaxis
Angioedema
Arthralgia
Asthenia
Attention disturbances
Back pain
Blistering
Blurred vision
Bronchospasm
Burning sensation
Chest pain
Colic
Conjunctivitis
Constipation
Cough
Decreased appetite
Depression
Diarrhoea
Dizziness
Drowsiness
Drug rash
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dyspnoea
Dysuria
Epistaxis
Erythema
Erythema multiforme
Facial oedema
Fatigue
Fever
Flatulence
Flushing
Gingival bleeding
Headache
Hyperesthesia
Hyperhidrosis
Hypersensitivity reactions
Hypoesthesia
Hypotension
Hypoxia
Increased partial thromboplastin time
Increases in serum transaminases (transient)
Influenza-like symptoms
Insomnia
Irritability
Jaw pain
Joint pain
Laryngeal discomfort
Lethargy
Light-headedness
Limb pain
Local burning
Lymphadenopathy
Malaise
Mucosal irritation
Myalgia
Nasal congestion
Nausea
Nightmares
Painful extremities
Palpitations
Peripheral oedema
Photophobia
Pleuritic pain
Pruritus
Pyrexia
Rash
Reduced lymphocyte count
Respiratory distress
Retching
Rigors
Skin tingling
Syncope
Tachycardia
Ulceration
Urticaria
Vertigo
Vomiting

Effects on Laboratory Tests

Mesna may cause false positive reactions in nitroprusside sodium-based urine tests for ketone bodies. The addition of glacial acetic acid can be used to differentiate between a false positive result (cherry-red colour that fades) and a true positive result (red-violet colour that intensifies).
A false positive reaction in Tillman's reagent-based urine screening tests for ascorbic acid may occur after mesna therapy. Serum creatine phosphokinase values may be lower in samples taken 24 hours after mesna dosing than in pre-dosing samples, which may have an impact on thiol dependent enzymatic creatine phosphokinase tests.

Patients with a history of a hypersensitivity reaction may show positive delayed-type skin test results. However, a negative delayed reaction does not exclude dermal hypersensitivity to mesna. Positive immediate-type skin test reactions have occurred in patients without prior mesna exposure nor history of hypersensitivity reactions, and may be related to the concentration of the mesna solution used for testing.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Mesna tablets 400 mg. Baxter Healthcare Ltd. Revised October 2014

Summary of Product Characteristics: Mesna tablets 600 mg. Baxter Healthcare Ltd. Revised October 2014

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 August 2017