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Vaprisol

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Vaprisol

Vaprisol

SIDE EFFECTS

The following adverse reactions are discussed elsewhere in labeling:

  • Osmotic demyelination syndrome [see WARNINGS AND PRECAUTIONS]
  • Infusion site reactions [see WARNINGS AND PRECAUTIONS]

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 and WARNINGS AND PRECAUTIONS].

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 Hyponatremia and Healthy Volunteer Studies

Term Placebo
(N=69)
N (%)
20 mg
(N=37)
N (%)
40 mg
(N=315)
N (%)
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%)
Adapted from MedDRA version 6.0

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].

Read the Vaprisol (conivaptan hcl injection) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

CYP3A

Conivaptan is a sensitive substrate of CYP3A. The effect of ketoconazole, a potent CYP3A inhibitor, on the pharmacokinetics of intravenous conivaptan has not been evaluated. Coadministration of oral conivaptan hydrochloride 10 mg with ketoconazole 200 mg resulted in 4- and 11-fold increases in Cmax and AUC of conivaptan, respectively [see CONTRAINDICATIONS].

Conivaptan is a potent mechanism-based inhibitor of CYP3A. The effect of conivaptan on the pharmacokinetics of co-administered CYP3A substrates has been evaluated with the coadministration of conivaptan with midazolam, simvastatin, and amlodipine. VAPRISOL 40 mg/day increased the mean AUC values by approximately 2- and 3-fold for 1 mg intravenous or 2 mg oral doses of midazolam, respectively. VAPRISOL 30 mg/day resulted in a 3-fold increase in the AUC of simvastatin. Oral conivaptan hydrochloride 40 mg twice daily resulted in a 2-fold increase in the AUC and half-life of amlodipine [see WARNINGS AND PRECAUTIONS].

Digoxin

Coadministration of a 0.5 mg dose of digoxin, a P-glycoprotein substrate, with oral conivaptan hydrochloride 40 mg twice daily resulted in a 30% reduction in clearance and 79% and 43% increases in digoxin Cmax and AUC values, respectively [see WARNINGS AND PRECAUTIONS].

Warfarin

VAPRISOL (40 mg/day for 4 days) administered with a single 25 mg dose of warfarin, which undergoes major metabolism by CYP2C9 and minor metabolism by CYP3A, increased the mean S-warfarin AUC and S-warfarin Cmax by 14% and 17%, respectively. The corresponding prothrombin time and international normalized ratio values were unchanged.

Captopril and Furosemide

The pharmacokinetics of oral conivaptan (20 - 40 mg/day) were unchanged with coadministration of either captopril 25 mg or furosemide up to 80 mg/day.

Last reviewed on RxList: 2/28/2012
This monograph has been modified to include the generic and brand name in many instances.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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