"ATLANTA, GA â€” The Centers for Disease Control and Prevention (CDC) has issued a warning for healthcare providers and patients to be aware of a potential risk of infection from certain devices used during many open-heart surgeries.
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
|Blood and lymphatic system disorders|
|Anemia NOS||2 (3%)||2 (5%)||18 (6%)|
|Atrial fibrillation||0 (0%)||2 (5%)||7 (2%)|
|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%)|
|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%)|
|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%)|
|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
CYP3A Inhibitors And Substrates
Conivaptan is a sensitive substrate of CYP3A. Coadministration with strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, ritonavir and indinavir) increases conivaptan exposure and is contraindicated [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].
Coadministration with CYP3A substrates results in increased exposure of the other drug. Avoid concomitant use with drugs eliminated primarily by CYP3A-mediated metabolism. Subsequent treatment with CYP3A substrates may be initiated no sooner than 1 week after the infusion of VAPRISOL is completed [see CLINICAL PHARMACOLOGY].
Coadministration of digoxin with oral conivaptan resulted in a 1.8-and 1.4-fold increase in digoxin Cmax and AUC, respectively. Monitor digoxin levels.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/7/2016
Additional Vaprisol Information
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