Mesna (generic name: mesna) is a medication used in medicine to prevent or reduce the risk of certain side effects associated with the use of a class of chemotherapy drugs called alkylating agents, specifically drugs like cyclophosphamide and ifosfamide. These drugs are often used in the treatment of various cancers, including bladder cancer, ovarian cancer, and lymphomas.

The main purpose of mesna is to protect the bladder from the toxic effects of these chemotherapy drugs, which can cause irritation and damage to the bladder lining, leading to a condition known as hemorrhagic cystitis. Mesna works by binding to and inactivating the harmful metabolites produced when these chemotherapy drugs are broken down in the body. By doing so, it reduces the risk of bladder toxicity and related complications.

Mesna (Ifomes, Mesnex) is available as an oral and intravenous formulation. It is a chemo-protectant and is used to prevent ifosfamide or cyclophosphamide-induced hemorrhagic cystitis.

Mesna (Ifomes, Mesnex) Uses:

• Prevention of ifosfamide-induced hemorrhagic cystitis:
  • Used in the Preventive agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis.
  • Limitations of use: Mesna is not indicated to reduce the hazard of hematuria due to other conditions such as thrombocytopenia
• Off label Use of Mensa (Ifomes) in Adults:
  • Used in the prevention of cyclophosphamide-induced hemorrhagic cystitis (with high-dose cyclophosphamide)
  • Used in the prevention of cyclophosphamide-induced hemorrhagic cystitis in patients with rheumatic or autoimmune disorders

Mesna (Ifomes, Mesnex) Dose in Adults:

Note:

• Mesna is a medicine given alongside a chemotherapy drug named ifosfamide.
• It's given to protect the bladder from damage.
• If the dose of ifosfamide changes, the dose of mesna should also change to keep them in balance.
• Every day you get ifosfamide, you also need mesna.

Mesna (Ifomes) Dose in the Prevention of ifosfamide-induced hemorrhagic cystitis:

• Standard-dose ifosfamide:
  • Given through IV (injection).
  • Take 3 doses of mesna every day, with each dose being 20% of the ifosfamide dose. These are taken when you get ifosfamide, 4 hours later, and then 8 hours after the ifosfamide.
• Oral mesna (after an IV dose and for low ifosfamide doses):
  • Start with an IV dose of mesna that's 20% of the ifosfamide dose.
  • Then, take two oral doses of mesna that are each 40% of the ifosfamide dose (2 and 6 hours after getting ifosfamide).
  • If you throw up within 2 hours of taking the oral dose, take it again or get an IV dose.
• Short infusion ifosfamide:
  • Given through IV.
  • Take mesna three times: 15 minutes before ifosfamide, and then 4 and 8 hours after ifosfamide. Each dose is 20% of the ifosfamide dose.
• Continuous infusion ifosfamide:
  • Given through IV.
  • Start with a single dose of mesna that's 20% of the ifosfamide dose.
  • Then, continuously get mesna that's 40% of the ifosfamide dose, and this goes on for 12 to 24 hours after the ifosfamide ends.
• High-dose ifosfamide:
  • Using mesna with high doses of ifosfamide isn't well-studied. If used, more frequent and prolonged mesna doses might be needed.
• Other methods (not the standard way):
  • Continuous infusion: Given through IV. The dose is equal to the ifosfamide dose and is given the whole time you're getting ifosfamide.
  • Bolus then continuous infusion: Start with a single IV dose of mesna, then get a continuous dose that's equal to the ifosfamide dose for 3 days.

Mesna Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis (in patients with cancer; off-label):

• For Ewing sarcoma (a type of cancer) using the HDCAV/IE regimen:
  • During cycles with cyclophosphamide (Cycles 1, 2, 3, and 6):
    • Adults below 40 years of age get a continuous IV (injection) dose of mesna.
    • The mesna dose each day is 2.1 g/m^2, which is the same as the cyclophosphamide dose they get.
    • This mesna dose is given for 2 days whenever cyclophosphamide is given during these cycles.
  • During cycles with ifosfamide (Cycles 4, 5, and 7):
    • The mesna dose each day is 1.8 g/m^2, which matches the ifosfamide dose.
    • This dose is given as a continuous IV for 5 days whenever ifosfamide is given during these cycles.
• For acute lymphocytic leukemia (a type of blood cancer) using the Hyper-CVAD regimen:
  • Patients get a continuous IV dose of mesna.
  • The daily dose is 600 mg/m^2, which is the same as the daily dose of cyclophosphamide.
  • Mesna is given on days 1, 2, and 3 of odd-numbered cycles (like Cycles 1, 3, 5, and 7).
  • The mesna dose starts with the cyclophosphamide dose and ends 6 hours after the last cyclophosphamide dose.

Mesna (Ifomes) Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis in patients with rheumatic or autoimmune disorders (off-label; based on limited data):

• When given through IV (injection):
  • Mesna is given 3 times:
    • First, 15 to 30 minutes before taking cyclophosphamide.
    • Then, 4 hours after cyclophosphamide.
    • Lastly, 8 hours after cyclophosphamide.
  • Each of these mesna doses is 20% of the daily cyclophosphamide dose.
• If taking Mesna orally:
  • Mesna is taken 3 times:
    • First, 2 hours before taking cyclophosphamide.
    • Then, 4 hours after cyclophosphamide.
    • Lastly, 8 hours after cyclophosphamide.
  • Each of these oral doses is 40% of the daily cyclophosphamide dose.
• Another method (based on a different study):
  • Mesna is given 3 times:
    • First, 3 hours after taking cyclophosphamide.
    • Then, 6 hours after cyclophosphamide.
    • Lastly, 8 hours after cyclophosphamide.
  • Each dose is 20% of the daily cyclophosphamide dose.
  • This schedule is followed each day for 4 days.

Mesna (Ifomes, Mesnex) Dose in Children:

Note: Dose, frequency, number of doses, and start date may vary by protocol and treatment phase. Refer to individual protocols.

Mesna (Ifomes) Dose in the Prevention of ifosfamide-induced hemorrhagic cystitis:

• Standard-dose ifosfamide:
  • IV (injection):
    • Mesna is given 3 times: with the ifosfamide dose, then 4 hours later, and 8 hours later.
    • Each time, the dose is 20% of the ifosfamide dose. So, the total daily Mesna dose is 60% of the ifosfamide dose.
    • But for ifosfamide doses more than 2000 mg/m^2/day, the safety and effectiveness aren't well-established.
• Alternate dosing (not the main method but still used):
  • Short IV infusion: Mesna is given in 3 parts, each 20% of the ifosfamide dose - first 15 minutes before ifosfamide, then 4 and 8 hours after starting ifosfamide.
  • Continuous IV infusion: Start with a 20% dose, then continuously give 40% of the ifosfamide dose. Keep giving Mesna for 12 to 24 hours after finishing ifosfamide.
  • Oral: Start with a 20% IV dose, then take two oral doses each at 40% of the ifosfamide dose, 2 and 6 hours after starting ifosfamide. Note: Oral doses are typically double the IV doses.
• High-dose ifosfamide:
  • The right dose isn't clear yet, and doctors might give Mesna more often or for longer times.
  • Some clinics give Mesna as short IV doses, 5 times (every 3 hours) after starting ifosfamide or continuously, starting before ifosfamide and ending 12 hours after ifosfamide.
• Other specific ways Mesna is used (based on certain treatment plans):
  • Continuous IV infusion: Mesna is given continuously, with a dose that matches the ifosfamide dose. This is repeated every day ifosfamide is given.
  • Bolus then continuous IV infusion: Start with a single dose, then continuously give Mesna that's equal to the ifosfamide dose for 3 days.
  • Mesna higher than ifosfamide: Mesna is given continuously for 4 days, and the dose is 20% more than the ifosfamide dose.

Mesna (Ifomes) Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis:

General Points:

• Mesna dosage is typically given every day cyclophosphamide is taken.
• If the cyclophosphamide dose changes, the Mesna dose should be adjusted too, to keep their ratio the same.

• Standard (low) dose cyclophosphamide (less than 1800 mg/m^2/day):
  • IV (Injection): Dosages vary but are usually 60%-100% of the daily cyclophosphamide dose. Some treatments even go up to 160%.
  • Short IV infusion:
    • Some places give Mesna in 3 parts, each time being 20% of the cyclophosphamide dose at 0, 4, and 8 hours after starting cyclophosphamide.
    • Others give Mesna in 5 parts, equally spaced out over 12 hours, starting when cyclophosphamide is given.
  • Continuous IV infusion: Mesna is given continuously starting 15-30 minutes before cyclophosphamide and ending 8 hours after the cyclophosphamide is finished.
  • Oral: After an initial 20% IV dose, two oral doses of Mesna are given, which are each 40% of the cyclophosphamide dose. They're taken 2 and 6 hours after starting cyclophosphamide. Note: The oral dose is usually double the IV dose.
• High dose cyclophosphamide (equal to or more than 1800 mg/m^2/day):
  • IV: Mesna is given in 5 equal parts spread over 12 hours, starting when cyclophosphamide starts.
  • Continuous IV infusion: Mesna is given continuously starting 15-30 minutes before the cyclophosphamide.
• Other specific treatment plans:
  • HDCAV/IE for Ewing sarcoma: Mesna is given as a continuous IV infusion. The daily dose is the same as the cyclophosphamide dose. This is given for 2 days when cyclophosphamide is taken during specific cycles (cycles 1, 2, 3, and 6).

Mesna Pregnancy Category: B

• Some studies have reported the use of Mesna to reduce the risk of bladder problems caused by ifosfamide in pregnant women.
• Mesna injections contain a preservative called benzyl alcohol, but it's believed that the fetus won't be exposed to it because the mother's body quickly breaks it down.
• However, it's essential to verify if a woman is pregnant before starting treatment with Mesna and ifosfamide.
• Women who can become pregnant should use effective birth control during their Mesna and ifosfamide treatment and for 6 months after their last dose.
• Men whose female partners can become pregnant should also use effective birth control during the treatment and for 3 months after the last dose.

Mesna (Ifomes) use during breastfeeding:

• We don't know if Mesna gets into breast milk.
• Some Mesna formulas have benzyl alcohol. While the mother's body breaks this down quickly, it might affect premature or low-weight babies when given directly through an IV.
• Given the risks, mothers are advised not to breastfeed during Mesna treatment and for at least 1 week after the last Mesna injection.
• Moreover, Mesna is often used with other strong drugs (cytotoxic agents) that could harm a breastfeeding baby.
• So, if a mother is on Mesna, it's important to be cautious and avoid breastfeeding during this time.

Ifomes Dose in Kidney Disease:

The manufacturer hasn't provided any specific dose changes for Mesna in people with kidney problems, because it hasn't been studied for that situation.

Ifomes Dose in Liver disease:

The manufacturer hasn't given any special dosing instructions for Mesna in people with liver problems, because this hasn't been researched.

Side effects of Mesna (Ifomes):

• Cardiovascular:
  • Flushing
• Central nervous system:
  • Dizziness
  • Drowsiness
  • Headache
  • Hyperesthesia
  • Rigors
• Dermatologic:
  • Skin rash
• Gastrointestinal:
  • Anorexia
  • Constipation
  • Diarrhea
  • Dysgeusia (with oral administration)
  • Flatulence
  • Nausea
  • Unpleasant taste (with oral administration)
  • Vomiting
• Local:
  • Injection site reaction
• Neuromuscular & skeletal:
  • Arthralgia
  • Back pain
• Ophthalmic:
  • Conjunctivitis
• Respiratory:
  • Cough
  • Flu-like symptoms
  • Pharyngitis Rhinitis
• Miscellaneous:
  • Fever

Contraindications to Mesna (Ifomes):

If someone is allergic to Mesna or any of its ingredients, they shouldn't take it.

Warnings and precautions

Dermatologic toxicities:

• Some people have experienced serious skin reactions after taking Mesna.
• These reactions can include a severe skin rash, itching, redness, burning, swelling around the eyes, facial flushing, and mouth sores.
• These side effects might happen the first time someone takes Mesna or after they've been on it for several months.
• If someone has a severe skin reaction to Mesna, they should stop taking it and get medical care right away.

Hematuria

• Keep an eye on the patient's urine for blood.
• If there's a lot of blood in the urine even after using Mesna, consider reducing the dose of ifosfamide (or cyclophosphamide) or stopping it altogether.
• Before starting ifosfamide (or cyclophosphamide) treatment, check the urine.
• If significant blood is found in the urine, consider adjusting or stopping the ifosfamide/cyclophosphamide treatment.
• It's important to note that Mesna might not prevent bladder issues in everyone.
• Also, make sure the patient drinks enough fluids during treatment.

Hypersensitivity

• Mesna can cause allergic reactions, which in some cases can be severe (like anaphylaxis).
• These reactions can include symptoms like fever, low blood pressure, fast heartbeat, kidney problems, difficulty breathing, skin rash, swelling, blood clotting issues, liver issues, nausea, vomiting, joint pain, and muscle pain.
• These reactions can happen the first time someone takes Mesna or after they've been on it for several months.
• Keep an eye on patients for these symptoms.
• If someone has an allergic reaction to Mesna, they should stop taking it and get medical care right away.
• It's also worth noting that Mesna contains a type of compound called a thiol.
• It's unclear if people who've had reactions to other thiol drugs (like amifostine) might be more likely to react to Mesna.

Ifosfamide/cyclophosphamide toxicities:

• Mesna is used to help prevent bladder problems caused by ifosfamide or cyclophosphamide.
• However, it won't protect against or treat any other side effects these drugs might cause.

Monitoring parameters:

• Urine Checks:
  • Look for blood in the urine (hematuria).
  • Keep track of how much urine is produced.
• Hydration:
  • Ensure the patient is drinking enough water and is well-hydrated.
• Pregnancy Checks:
  • Confirm if a woman can become pregnant before starting treatment.
• Allergic Reactions:
  • Watch for signs or symptoms of an allergic reaction.
• Skin Reactions:
  • Look for signs of skin problems or reactions.

How to administer Mesna (Ifomes)?

• Hydration:
  • Ensure the patient drinks enough water and produces a regular amount of urine when taking ifosfamide (or cyclophosphamide).
• IV (Injection) Administration:
  • Give Mesna directly as an IV shot as recommended by the manufacturer.
  • Mesna can also be given over a short period or as a continuous drip. If given continuously, keep it going for 12 to 24 hours after finishing the ifosfamide treatment. Refer to the specific treatment plan for more details.
• Oral Administration:
  • Give Mesna as a tablet.
  • If a patient throws up within 2 hours after taking the tablet, they should take another one or get Mesna as an IV shot.
  • If needed, Mesna can be mixed into syrup, juice, carbonated drinks, or milk to make a drinkable solution. Refer to guidelines for making this mix.

Mechanism of action of Mesna (Ifomes):

• In the bloodstream, Mesna turns into another substance called dimesna.
• When dimesna reaches the kidneys, it changes back into Mesna.
• This Mesna now has a special part called a free thiol group.
• This free thiol group grabs onto and neutralizes acrolein.
• Acrolein is a harmful byproduct created when the body processes ifosfamide and cyclophosphamide, and it can damage the bladder.
• By neutralizing acrolein, Mesna helps protect the bladder from damage.

Distribution:

• Mesna spreads out in the body at a rate of 0.65 ± 0.24 L/kg, which means it's distributed mainly through the body's water content.

Protein Binding:

• 69% to 75% of Mesna attaches to proteins in the blood.

Metabolism:

• Mesna quickly changes to a substance called dimesna in the blood.
• Neither Mesna nor dimesna get changed in the liver.

How Much the Body Uses (Bioavailability):

• For oral Mesna (taken by mouth), the body can use about 58% of it (this can vary between 45% to 71%).
• Eating doesn't affect how much Mesna the body can use.

How Long It Lasts (Half-life):

• Mesna stays in the body for about 22 minutes.
• Dimesna, its altered form, lasts around 70 minutes.

When It Peaks in the Blood:

• For oral Mesna, it reaches its highest level:
  • After 1.5 to 4 hours for free Mesna.
  • After 3 to 7 hours for total Mesna.

How It Leaves the Body (Excretion):

• It's removed through urine. Around 32% leaves as Mesna and 33% as dimesna.

International Brand Names of Mesna:

• Mesnex
• Uromitexan
• Delinar
• Ifomes
• Mescryo
• Mesnil
• Mesodal
• Mistabron
• Mitexan
• Mucofluid
• Novacarel
• Uromes
• Uromitexan
• Uroprot

Mesna Brand Names in Pakistan: