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Mesnex
Classes
Cytoprotectant Agents
Administration
Patients who vomit within 2 hours of oral mesna should repeat the oral dose or receive an intravenous dose.
Oral administration of mesna is only recommended in patients with good compliance and when emesis is controlled.
Mesna tablets are given orally without regard to meals or food.
Mesna injection may be diluted 1:1 to 1:10 in carbonated cola drinks or chilled fruit juice such as apple, grape, tomato, or orange juice for oral administration. Plain or chocolate milk has also been used. Due to the sulfur odor (rotten eggs) of the mesna injection, more dilute solutions may be better tolerated.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Mesna injection should be diluted to obtain a final concentration of 20 mg/ml.
Mesna may be given as a rapid IV infusion/bolus or as a continuous infusion.
Mesna is compatible with cyclophosphamide and ifosfamide in the same infusion fluid and may be admixed for continuous infusion.
Diluted solutions are chemically and physically stable for 24 hours at room temperature, 77 degrees F (25 degrees C). Mesna multidose vials may be stored and used for up to 8 days.
Adverse Reactions
seizures / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
constipation / Delayed / 17.6-23.5
leukopenia / Delayed / 17.6-21.0
anemia / Delayed / 16.8-17.6
thrombocytopenia / Delayed / 13.4-17.6
chest pain (unspecified) / Early / 8.4-9.2
hypokalemia / Delayed / 8.4-9.2
dyspnea / Early / 9.2-9.2
edema / Delayed / 6.7-7.6
hematuria / Delayed / 5.9-6.7
peripheral edema / Delayed / 6.7-6.7
sinus tachycardia / Rapid / 0.8-5.9
confusion / Early / 5.0-5.9
dehydration / Delayed / 2.5-5.9
hypotension / Rapid / 3.4-5.0
hypertension / Early / Incidence not known
dysuria / Early / Incidence not known
colic / Delayed / Incidence not known
hyperesthesia / Delayed / Incidence not known
photophobia / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
hypoxia / Early / Incidence not known
skin ulcer / Delayed / Incidence not known
erythema / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
bullous rash / Early / Incidence not known
hepatitis / Delayed / Incidence not known
nausea / Early / 53.8-54.6
vomiting / Early / 29.4-37.8
fatigue / Early / 20.2-20.2
fever / Early / 15.1-20.2
anorexia / Delayed / 16.0-17.6
asthenia / Delayed / 12.6-17.6
abdominal pain / Early / 11.8-15.1
diarrhea / Early / 7.6-14.3
headache / Early / 7.6-10.9
alopecia / Delayed / 10.1-10.9
drowsiness / Early / 6.7-10.1
insomnia / Early / 5.0-9.2
injection site reaction / Rapid / 6.7-8.4
cough / Delayed / 4.2-8.4
dizziness / Early / 4.2-7.6
hyperhidrosis / Delayed / 1.7-7.6
back pain / Delayed / 5.0-6.7
anxiety / Delayed / 3.4-5.9
dyspepsia / Early / 3.4-5.0
flushing / Rapid / 0.8-5.0
pallor / Early / 3.4-5.0
flatulence / Early / Incidence not known
xerostomia / Early / Incidence not known
dysgeusia / Early / Incidence not known
malaise / Early / Incidence not known
paresthesias / Delayed / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
rhinitis / Early / Incidence not known
influenza / Delayed / Incidence not known
chills / Rapid / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
Common Brand Names
Mesnex
Dea Class
Rx
Description
Chemoprotectant against hemorrhagic cystitis; more effective prophylaxis than fluids, diuretics, forced diuresis, and intravesical administration of other sulfhydryl-compounds; does not interfere with the antitumor activity of ifosfamide or cyclophosphamide.
Dosage And Indications
NOTE: Mesna has been designated an orphan drug by the FDA for this indication.
Administer mesna IV at a dosage of at least 20% (w/w) of the ifosfamide dosage 15 minutes before ifosfamide administration. Then give the same dose 4 and 8 hours after ifosfamide administration. Total daily mesna dosage is at least 60% of the ifosfamide dosage. For high-dose ifosfamide therapy, a mesna dose of 20% of the ifosfamide dosage IV has been administered 15 minutes before ifosfamide administration and then every 3 hours for 3 to 6 doses. A similar regimen may be used for high-dose cyclophosphamide therapy.
Administer a mesna IV bolus at a dose of 10% (w/w) of the ifosfamide dosage 15 minutes before beginning the continuous IV infusion, then follow with a continuous IV infusion of mesna at a dose of 100% (w/w) of the ifosfamide dosage. Generally, mesna is continued as an IV infusion for 24 hours after the completion of ifosfamide.
At the time of ifosfamide administration, give a single dose of mesna IV at a dose of 20% (w/w) of the ifosfamide dosage, then mesna tablets PO in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of mesna is 100% of the ifosfamide dose.
Following an initial IV bolus, mesna injection PO is given at a dosage of 40% (w/w) of the ifosfamide dose 4 and 8 hours after ifosfamide administration. It is not recommended to give mesna orally as the initial dose.
Dosing Considerations
No dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
There are no drug interactions associated with Mesna products.
How Supplied
Mesna/Mesnex Intravenous Inj Sol: 1mL, 100mg
Mesnex Oral Tab: 400mg
Maximum Dosage
Specific maximum dosage information is not available. Individualize dosage based on dose of ifosfamide or cyclophosphamide.
Mechanism Of Action
Mechanism of Action: Mesna forms thioether bonds with acrolein, 4-hydroxy-ifosfamide and chloracetaldehyde, which are the urotoxic metabolites of oxazaphosphorine agents. Within the kidney mesna reacts with acrolein. The acrolein-mesna thioether complex is inactive and eliminated in the urine without causing hemorrhagic cystitis. Mesna also blocks or stabilizes the breakdown of 4-hydroxy-ifosfamide in the bladder preventing the formation of more acrolein. Mesna will not prevent non-urologic toxicities.
Pharmacokinetics
Mesna is administered intravenously (IV) or orally. Mesna is metabolized to dimesna (2,2'-dithio-bis-ethane sulfonate) by oxidative, metal-catalyzed reactions. Dimesna does not distribute outside the intravascular space and is rapidly excreted by the kidney. There is virtually no hepatic metabolism of mesna. Mesna is filtered by the glomeruli, reabsorbed by the proximal tubule, and then secreted back in the tubule of the kidney. In the renal epithelium, dimesna is reduced to mesna by thiol transferase and glutathione reductase. Following IV administration mesna and dimesna have half-lives of 10.2 minutes and 66 minutes, respectively. The majority of the IV dose is eliminated within 4 hours. The half-life of mesna ranged from 1.2—8.3 hours after administration of IV plus oral doses. Approximately 5% of the mesna dose given as the IV and oral regimen is excreted during the 12—24 hour period as compared to negligible amounts in patients given the IV regimen.
The urinary bioavailability of oral mesna ranged from 45—79% of IV mesna. Food does not affect the urinary bioavailability of oral mesna. Protein binding of mesna is moderate (69—75%). When compared to IV mesna, the IV plus oral regimen increases systemic exposure (150%) and provides more sustained excretion of mesna in the urine over a 24-hour period.
When compared to IV mesna, the IV plus oral regimen increases systemic exposure (150%) and provides more sustained excretion of mesna in the urine over a 24-hour period.
Pregnancy And Lactation
No adequate and well-controlled studies have been performed in pregnant women, and its ability to cause fetal harm or affect reproductive capacity is unknown. Two case reports have described the use of mesna, in combination with chemotherapeutic agents, during pregnancy. In the first report, a 21-year-old woman was treated with three courses of chemotherapy plus mesna (5 gm/m2 three times weekly) during the third trimester. The patient underwent a cesarean section at gestational week 36; no adverse effects were noted in the infant at delivery or during follow up at age 2 years.[49545] The second patient was a 20-year-old who began chemotherapy and mesna treatment at gestational week 23. Prior to treatment, the fetal weight was at the 20th percentile and fetal movement and amniotic fluid volume was normal; however, an ultrasound on week 4 of treatment revealed an absence of amniotic fluid, cessation of fetal growth, and an absence of fetal movement. Two weeks later (gestational week 29), the infant was born via an emergency cesarean section and died at age 7 days. An association with mesna was not able to be established.[49546] The manufacturer recommends use during pregnancy only if needed.[49539]
Mesna is used in combination with ifosfamide and other cytotoxic agents; therefore, it is advised that women of reproductive potential undergo pregnancy testing before receiving treatment. In addition, instruct drug recipients of contraception requirements that include use of an effective contraception for 6 months after the last mesna/ifosfamide dose for women and 3 months after the last dose for men.[49539] [57332]