openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Hypervolemic hyponatremia associated with heart failure : Data are limited. Consider other treatment options ( 5.1 , 6.1 ). Overly rapid correction of serum sodium : Monitor serum sodium and neurologic status as serious neurologic sequelae can result from over rapid correction of serum sodium ( 2.1 , 5.2 ). Infusion site reactions : Serious reactions have occurred. Administer through large veins and change infusion site every 24 hours ( 2.1 , 5.4 , 6 ). 5.1 Hyponatremia Associated with Heart Failure The amount of safety data on the use of VAPRISOL in patients with hypervolemic hyponatremia associated with heart failure is limited. VAPRISOL should be used to raise serum sodium in such patients only after consideration of other treatment options [see Adverse Reactions ( 6.1 )] . 5.2 Overly Rapid Correction of Serum Sodium Osmotic demyelination syndrome is a risk associated with overly rapid correction of hyponatremia (i.e., > 12 mEq/L/24 hours). Osmotic demyelination results in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma or death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, use slower rates of correction. In controlled clinical trials of VAPRISOL, about 9% of patients who received VAPRISOL in doses of 20-40 mg/day IV had rises of serum sodium >12 mEq/L/24 hours, but none of these patients had evidence of osmotic demyelination or permanent neurologic sequelae. Serum sodium concentration and neurologic status should be monitored appropriately during VAPRISOL administration, and VAPRISOL administration should be discontinued if the patient develops an undesirably rapid rate of rise of serum sodium. If the serum sodium concentration continues to rise, VAPRISOL should not be resumed. If hyponatremia persists or recurs (after initial discontinuation of VAPRISOL for an undesirably rapid rate of rise of serum sodium concentration), and the patient has had no evidence of neurologic sequelae of rapid rise in serum sodium, VAPRISOL may be resumed at a reduced dose [see Dosage and Administration ( 2.1 )] . 5.3 Hypovolemia or Hypotension For patients who develop hypovolemia or hypotension while receiving VAPRISOL, VAPRISOL should be discontinued, and volume status and vital signs should be frequently monitored. Once the patient is again euvolemic and is no longer hypotensive, VAPRISOL may be resumed at a reduced dose if the patient remains hyponatremic. 5.4 Infusion Site Reactions Infusion site reactions are common and can include serious reactions, even with proper infusion rates [see Adverse Reactions ( 6.1 )] . Administer VAPRISOL via large veins, and rotate the infusion site every 24 hours [see Dosage and Administration ( 2.1 )] .
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in labeling: Osmotic demyelination syndrome [see Warnings and Precautions ( 5.2 )] Infusion site reactions [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (incidence ≥ 10%) are infusion site reactions (including phlebitis), pyrexia, hypokalemia, headache and orthostatic hypotension ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc. at 1-887-484-2700 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 reactions 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. The adverse event information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. The most common adverse reactions reported with VAPRISOL administration were infusion site reactions. In studies in patients and healthy volunteers, infusion site reactions occurred in 73% and 63% of subjects treated with VAPRISOL 20 mg/day and 40 mg/day, respectively, compared to 4% in the placebo group. Infusion site reactions were the most common type of adverse event leading to discontinuation of VAPRISOL. Discontinuations from treatment due to infusion site reactions were more common among VAPRISOL-treated patients (3%) than among placebo-treated patients (0%). Some serious infusion site reactions did occur [see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.4 )] . The adverse reactions presented in Table 1 are derived from 72 healthy volunteers and 243 patients with euvolemic or hypervolemic hyponatremia who received VAPRISOL 20 mg IV as a loading dose followed by 40 mg/day IV for 2 to 4 days, from 37 patients with euvolemic or hypervolemic hyponatremia who received VAPRISOL 20 mg IV as a loading dose followed by 20 mg/day IV for 2 to 4 days in an open-label study, and from 40 healthy volunteers and 29 patients with euvolemic or hypervolemic hyponatremia who received placebo. The adverse reactions occurred in at least 5% of patients treated with VAPRISOL and at a higher incidence for VAPRISOL-treated patients than for placebo-treated patients. Table 1. VAPRISOL Injection: Adverse Reactions Occurring in ≥ 5% of Patients or Healthy Volunteers and VAPRISOL Incidence > Placebo Incidence Term Placebo (N=69) N (%) 20 mg (N=37) N (%) 40 mg (N=315) N (%) Adapted from MedDRA version 6.0 Blood and lymphatic system disorders Anemia NOS 2 (3%) 2 (5%) 18 (6%) Cardiac disorders Atrial fibrillation 0 (0%) 2 (5%) 7 (2%) Gastrointestinal disorders Constipation 2 (3%) 3 (8%) 20 (6%) Diarrhea NOS 0 (0%) 0 (0%) 23 (7%) Nausea 3 (4%) 1 (3%) 17 (5%) Vomiting NOS 0 (0%) 2 (5%) 23 (7%) General disorders and administration site conditions Edema peripheral 1 (1%) 1 (3%) 24 (8%) Infusion site erythema 0 (0%) 0 (0%) 18 (6%) Infusion site pain 1 (1%) 0 (0%) 16 (5%) Infusion site phlebitis 1 (1%) 19 (51%) 102 (32%) Infusion site reaction 0 (0%) 8 (22%) 61 (19%) Pyrexia 0 (0%) 4 (11%) 15 (5%) Thirst 1 (1%) 1 (3%) 19 (6%) Infections and infestations Pneumonia NOS 0 (0%) 2 (5%) 7 (2%) Urinary tract infection NOS 2 (3%) 2 (5%) 14 (4%) Injury, poisoning and procedural complications Post procedural diarrhea 0 (0%) 2 (5%) 0 (0%) Investigations Electrocardiogram ST segment depression 0 (0%) 2 (5%) 0 (0%) Metabolism and nutrition disorders Hypokalemia 2 (3%) 8 (22%) 30 (10%) Hypomagnesemia 0 (0%) 2 (5%) 6 (2%) Hyponatremia 1 (1%) 3 (8%) 20 (6%) Nervous system disorders Headache 2 (3%) 3 (8%) 32 (10%) Psychiatric disorders Confusional state 2 (3%) 0 (0%) 16 (5%) Insomnia 0 (0%) 2 (5%) 12 (4%) Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain 3 (4%) 2 (5%) 3 (1%) Skin and subcutaneous tissue disorders Pruritus 0 (0%) 2 (5%) 2 (1%) Vascular disorders Hypertension NOS 0 (0%) 3 (8%) 20 (6%) Hypotension NOS 2 (3%) 3 (8%) 16 (5%) Orthostatic hypotension 0 (0%) 5 (14%) 18 (6%) Although a dose of 80 mg/day of VAPRISOL was also studied, it was associated with a higher incidence of infusion site reactions and a higher rate of discontinuation for adverse events than was the 40 mg/day VAPRISOL dose. The maximum recommended daily dose of VAPRISOL (after the loading dose) is 40 mg/day. Heart failure with hypervolemic hyponatremia In clinical trials where VAPRISOL was administered to 79 hypervolemic hyponatremic patients with underlying heart failure and intravenous placebo administered to 10 patients, adverse cardiac failure events, atrial dysrhythmias, and sepsis occurred more frequently among patients treated with VAPRISOL (32%, 5% and 8% respectively) than among patients treated with placebo (20%, 0% and 0% respectively) [see Warnings and Precautions ( 5.1 )] .