Vaprisol

• Astellas Pharma US, Inc.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have:

• a light-headed feeling, like you might pass out;

• low potassium--confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling; or

• signs of a rapid increase in sodium levels--trouble speaking, trouble swallowing, weakness, mood changes, muscle spasm or weakness in your arms and legs, seizure.

Common side effects may include:

• fever;

• low potassium;

• headache, mild dizziness; or

• pain, redness, or swelling around the IV needle.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Arginine vasopressin (AVP) V1A and V2 antagonist.1 2 3 4 5 6 7

• V2 antagonism of AVP in renal collecting ducts results in increased free water excretion (i.e., effective water clearance); and, typically, increased net fluid loss, increased urine output, and decreased urine osmolality.1 2 3 6

• Blockade of vascular V1A receptors may cause splanchnic vasodilation, possibly resulting in hypotension or variceal bleeding in patients with cirrhosis (especially those with portal hypertension).3 9

• Does not appear to have a clinically important effect on cardiac repolarization.1

• Importance of advising patients of common adverse effects, including infusion site reactions (e.g., edema, erythema, pain, phlebitis), orthostatic hypotension (e.g., lightheadedness, syncope), pyrexia, hypokalemia, and headache.1

• Potential for too rapid an increase in serum sodium concentration, which may result in serious neurologic sequelae.1 Importance of informing clinician if any signs or symptoms suggestive of osmotic demyelination syndrome (e.g., difficulty speaking or swallowing, drowsiness, confusion, mood changes, weakness or involuntary movements in the extremities, seizures) occur.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.1

• Importance of alerting clinician if an allergy to corn or corn products exists.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

• If you need to store Vaprisol at home, talk with your doctor, nurse, or pharmacist about how to store it.

Hypovolemic Hyponatremia

Vaprisol is contraindicated in patients with hypovolemic hyponatremia.

Coadministration with Potent CYP3A Inhibitors

The coadministration of Vaprisol with potent CYP3A inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated [see Drug Interactions (7.1)].

Anuric Patients

In patients unable to make urine, no benefit can be expected [see Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard lifetime (104 week) carcinogenicity bioassays were conducted in mice and rats. Male and female mice were given oral doses of conivaptan hydrochloride up to 30 mg/kg/day and 10 mg/kg/day, respectively, by gavage. Male and female rats were given oral doses of up to 10 mg/kg/day and 30 mg/kg/day, respectively, by gavage. There was no increased incidence of tumors associated with exposure to conivaptan in either species. The 30 mg/kg/day dosage regimen in male mice and female rats was shown to result in a systemic exposure (AUC) about twice the human systemic exposure from an IV bolus of 20 mg on day 1 followed by IV infusion of 40 mg/day for 3 days. The 10 mg/kg/day dosage regimen in female mice and male rats was shown to result in about one-fourth and one-half the human therapeutic exposure, respectively.

Conivaptan was not genotoxic in the bacterial reverse mutation assay, the in vitro human peripheral blood lymphocyte chromosomal aberration assay, or in vivo rat micronucleus assay.

Fertility of male rats treated with conivaptan hydrochloride by IV bolus doses of up to 2.5 mg/kg/day for the 4 weeks preceding mating and throughout the mating period was unaffected. However, when female rats were given IV bolus conivaptan from 15 days before mating through gestation day 7, there was prolonged diestrus, decreased fertility (decreased numbers of corpora lutea and implantations) and increased post-implantation loss at 2.5 mg/kg/day (systemic exposure less than human exposure at the therapeutic dose).

Vaprisol (conivaptan hydrochloride) Injection is supplied as a single-use, premixed solution, containing 20 mg of conivaptan hydrochloride in 5% Dextrose in 100 mL INTRAVIA Plastic Containers.

• 1 container/carton (NDC 66220-160-10)

Vaprisol in INTRAVIA Plastic Containers should be stored at 25°C (77°F); however, brief exposure up to 40°C (104°F) does not adversely affect the product. Avoid excessive heat. Protect from freezing. Protect from light until ready to use.

Inform patients about the common adverse effects of Vaprisol including infusion site effects (edema, erythema, pain, and phlebitis), pyrexia, hypokalemia, headache, orthostatic hypotension and potential for overly rapid increase in serum sodium which can cause serious neurologic sequelae. Instruct patients to inform their healthcare provider if they develop any unusual symptoms, or if any known symptom persists or worsens, with special attention to potential manifestations of osmotic demyelination syndrome.

Ask patients about what other medications they are currently taking with Vaprisol, including over-the-counter medications.

Lactation

Advise women not to breastfeed during treatment with Vaprisol [see Use in Specific Populations (8.2)].

Marketed by:
Cumberland Pharmaceuticals Inc.
Nashville TN 37203

Vaprisol is a registered trademark of Cumberland Pharmaceuticals Inc.
INTRAVIA is a registered trademark of Baxter International Inc.

US Patent Number 5,723,606

07-19-73-925

Principal Display Panel - Box Label

NDC 66220-160-10

Vaprisol®

(conivaptan hydrochloride) injection

Premixed in 5% Dextrose

20 mg/100 mL (0.2 mg per mL)

100 mL

STERILE NONPYROGENIC

SINGLE-DOSE INTRAVIA CONTAINER

Principal Display Panel - Pouch Label

100 mL

2J1451

12B017-VAP

NDC 66220-160-10

Vaprisol®
(CONIVAPTAN HYDROCHLORIDE)

INJECTION

PREMIXED IN 5% DEXTROSE

20 mg/100 mL (0.2 mg per mL)

SINGLE-DOSE

INTRAVIA CONTAINER STERILE NONPYROGENIC

Since Vaprisol is given by a healthcare professional, you are not likely to miss a dose.

Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.