Mesna Side Effects

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling.

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)] • Dermatological Toxicity [see Warnings and Precautions (5.2)] • Benzyl Alcohol Toxicity [see Warnings and Precautions (5.3)] • Laboratory Test Interferences [see Warnings and Precautions (5.4)] • Use in Patients with a History of Adverse Reactions to Thiol Compounds [see Warnings and Precautions (5.5)] The most common adverse reactions (> 10%) when mesna injection is given with ifosfamide are nausea, vomiting, constipation, leukopenia, fatigue, fever, anorexia, thrombocytopenia, anemia, granulocytopenia, diarrhea, asthenia, abdominal pain, headache, alopecia, and somnolence.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Mesna injection adverse reaction data are available from four Phase 1 studies in which single intravenous doses of 600 to 1200 mg mesna injection without concurrent chemotherapy were administered to a total of 53 healthy volunteers and single oral doses of 600 to 2400 mg of mesna tablets were administered to a total of 82 healthy volunteers.

The most frequently reported side effects (observed in two or more healthy volunteers) for healthy volunteers receiving single doses of mesna injection alone were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-like symptoms, and coughing.

In two Phase 1 multiple-dose studies where healthy volunteers received mesna tablets alone or intravenous mesna followed by repeated doses of mesna tablets, flatulence and rhinitis were reported.

In addition, constipation was reported by healthy volunteers who had received repeated doses of intravenous mesna injection.

Additional adverse reactions in healthy volunteers receiving mesna injection alone included injection site reactions, abdominal pain/colic, epigastric pain/burning, mucosal irritation, lightheadedness, back pain, arthralgia, myalgia, conjunctivitis, nasal congestion, rigors, paresthesia, photophobia, fatigue, lymphadenopathy, extremity pain, malaise, chest pain, dysuria, pleuritic pain, dry mouth, dyspnea, and hyperhidrosis.

In healthy volunteers, mesna was commonly associated with a rapid (within 24 hours) decrease in lymphocyte count, which was generally reversible within one week of administration.