ADVERSE REACTIONS
Mesna adverse reaction data are available from four phase I studies in which single IV bolus doses of 600-1200 mg Mesna Injection without concurrent chemotherapy were administered to a total of 53 subjects and single oral doses of 600-2400 mg of Mesnex Tablets were administered to a total of 82 subjects.
The most frequently reported side effects (observed in two or more patients) for patients receiving single doses of Mesna IV were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperaesthesia, influenza-like symptoms, and coughing. Among patients who received a single 1200-mg dose as an oral solution, rigors, back pain, rash, conjunctivitis, and arthralgia were also reported. In two phase I multiple-dose studies where patients received Mesnex Tablets alone or IV Mesna followed by repeated doses of Mesnex Tablets, flatulence and rhinitis were reported. In addition, constipation was reported by patients who had received repeated doses of IV Mesna.
Because mesna is used in combination with ifosfamide or ifosfamide-containing chemotherapy regimens, it is difficult to distinguish the adverse reactions which may be due to Mesna from those caused by the concomitantly administered cytotoxic agents.
Adverse reactions reasonably associated with mesna administered IV and orally in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 3.
| Table 3 |
| Incidence of Adverse Events and Incidence of Most Frequently Reported Adverse Events in Controlled Studies |
| Mesna Regimen | IV-IV-IV | IV-Oral-Oral |
| N exposed | 119 (100.0%) | 119 (100.0%) |
| Incidence of AEs | 101 (84.9%) | 106 (89.1%) |
| Most Frequently Reported Adverse Events (Preferred Terms) |
| | N (%) | N (%) |
| Nausea | 65 (54.6) | 64 (53.8) |
| Vomiting | 35 (29.4) | 45 (37.8) |
| Constipation | 28 (23.5) | 21 (17.6) |
| Leukopenia | 25 (21.0) | 21 (17.6) |
| Fatigue | 24 (20.2) | 24 (20.2) |
| Fever | 24 (20.2) | 18 (15.1) |
| Anorexia | 21 (17.6) | 19 (16.0) |
| Thrombocytopenia | 21 (17.6) | 16 (13.4) |
| Anemia | 20 (16.8) | 21 (17.6) |
| Granulocytopenia | 16 (13.4) | 15 (12.6) |
| Asthenia | 15 (12.6) | 21 (17.6) |
| Abdominal Pain | 14 (11.8) | 18 (15.1) |
| Alopecia | 12 (10.1) | 13 (10.9) |
| Dyspnea | 11 (9.2) | 11 (9.2) |
| Chest Pain | 10 (8.4) | 9 (7.6) |
| Hypokalemia | 10 (8.4) | 11 (9.2) |
| Diarrhea | 9 (7.6) | 17 (14.3) |
| Dizziness | 9 (7.6) | 5 (4.2) |
| Headache | 9 (7.6) | 13 (10.9) |
| Pain | 9 (7.6) | 10 (8.4) |
| Sweating Increased | 9 (7.6) | 2 (1.7) |
| Back Pain | 8 (6.7) | 6 (5.0) |
| Hematuria* | 8 (6.7) | 7 (5.9) |
| Injection Site Reaction | 8 (6.7) | 10 (8.4) |
| Edema | 8 (6.7) | 9 (7.6) |
| Edema Peripheral | 8 (6.7) | 8 (6.7) |
| Somnolence | 8 (6.7) | 12 (10.1) |
| Anxiety | 7 (5.9) | 4 (3.4) |
| Confusion | 7 (5.9) | 6 (5.0) |
| Face Edema | 6 (5.0) | 5 (4.2) |
| Insomnia | 6 (5.0) | 11 (9.2) |
| Coughing | 5 (4.2) | 10 (8.4) |
| Dyspepsia | 4 (3.4) | 6 (5.0) |
| Hypotension | 4 (3.4) | 6 (5.0) |
| Pallor | 4 (3.4) | 6 (5.0) |
| Dehydration | 3 (2.5) | 7 (5.9) |
| Pneumonia | 2 (1.7) | 8 (6.7) |
| Tachycardia | 1 (0.8) | 7 (5.9) |
| Flushing | 1 (0.8) | 6 (5.0) |
| * All grades |
Postmarketing Surveillance
Allergic reactions, decreased platelet counts associated with allergic reactions, hypertension, hypotension, increased heart rate, increased liver enzymes, injection site reactions (including pain and erythema), limb pain, malaise, myalgia, ST-segment elevation, tachycardia, and tachypnea have been reported as part of postmarketing surveillance.
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