FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.
2 DOSAGE AND ADMINISTRATION
2.1 Administration
This product does not require dilution prior to administration.
In general, titrate to the lowest dose compatible with a clinically acceptable response.
The recommended starting dose is:
Post-cardiotomy shock: 0.03 units/minute by intravenous infusion
Septic Shock: 0.01 units/minute by intravenous infusion
Titrate up by 0.005 units/minute at 10- to 15-minute intervals until the target blood pressure is reached. There are limited data for doses above 0.1 units/minute for post-cardiotomy shock and 0.07 units/minute for septic shock. Adverse reactions are expected to increase with higher doses.
After target blood pressure has been maintained for 8 hours without the use of catecholamines, taper vasopressin injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.
Inspect visually for any particulate matter and discoloration prior to administration.
Discard Unused Portion
Do not add supplemental medication or additive
3 DOSAGE FORMS AND STRENGTHS
Injection: a clear, practically colorless solution for intravenous infusion, supplied in 100-mL single dose ready-to-use containers as:
- •
- 20 units vasopressin (0.2 units/mL) in 0.9% sodium chloride
- •
- 40 units vasopressin (0.4 units/mL) in 0.9% sodium chloride
4 CONTRAINDICATIONS
Vasopressin in Sodium Chloride Injection is contraindicated in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin.
5 WARNINGS AND PRECAUTIONS
5.1 Worsening Cardiac Function
A decrease in cardiac index may be observed with the use of vasopressin.
5.2 Reversible Diabetes Insipidus
Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts.
6 ADVERSE REACTIONS
The following adverse reactions associated with the use of vasopressin were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate reliably their frequency or establish a causal relationship to drug exposure.
Bleeding/lymphatic system disorders: Hemorrhagic shock, decreased platelets, intractable bleeding
Cardiac disorders: Right heart failure, atrial fibrillation, bradycardia, myocardial ischemia
Gastrointestinal disorders: Mesenteric ischemia
Hepatobiliary: Increased bilirubin levels
Renal/urinary disorders: Acute renal insufficiency
Vascular disorders: Distal limb ischemia
Metabolic: Hyponatremia
Skin: Ischemic lesions
Postmarketing Experience
Reversible diabetes insipidus [see Warnings and Precautions (5.2)]
7 DRUG INTERACTIONS
7.1 Catecholamines
Use with catecholamines is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.
7.2 Indomethacin
Use with indomethacin may prolong the effect of Vasopressin in Sodium Chloride Injection on cardiac index and systemic vascular resistance. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [see Clinical Pharmacology (12.3)].
7.3 Ganglionic Blocking Agents
Use with ganglionic blocking agents may increase the effect of Vasopressin in Sodium Chloride Injection on mean arterial blood pressure. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed [see Clinical Pharmacology (12.3)].
7.4 Drugs Suspected of Causing SIADH
Use with drugs suspected of causing SIADH (e.g., SSRIs, tricyclic antidepressants, haloperidol, chlorpropamide, enalapril, methyldopa, pentamidine, vincristine, cyclophosphamide, ifosfamide, felbamate) may increase the pressor effect in addition to the antidiuretic effect of Vasopressin in Sodium Chloride Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.
7.5 Drugs Suspected of Causing Diabetes Insipidus
Use with drugs suspected of causing diabetes insipidus (e.g., demeclocycline, lithium, foscarnet, clozapine) may decrease the pressor effect in addition to the antidiuretic effect of Vasopressin in Sodium Chloride Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on Vasopressin in Sodium Chloride Injection use in pregnant women to inform a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted.
Clinical Considerations
- Dose Adjustments During Pregnancy and the Postpartum Period: Because of increased clearance of vasopressin in the second and third trimester, the dose of Vasopressin in Sodium Chloride Injection may need to be increased [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
- Maternal Adverse Reactions: Vasopressin in Sodium Chloride Injection may produce tonic uterine contractions that could threaten the continuation of pregnancy.
8.2 Lactation
There are no data on the presence of vasopressin injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.
8.4 Pediatric Use
Safety and effectiveness of Vasopressin in Sodium Chloride Injection in pediatric patients with vasodilatory shock have not been established.
8.5 Geriatric Use
Clinical studies of vasopressin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Warnings and Precautions (5), Adverse Reactions (6), and Clinical Pharmacology (12.3)].
10 OVERDOSAGE
Overdosage with Vasopressin in Sodium Chloride Injection can be expected to manifest as consequences of vasoconstriction of various vascular beds (peripheral, mesenteric, and coronary) and as hyponatremia. In addition, overdosage may lead less commonly to ventricular tachyarrhythmias (including Torsade de Pointes), rhabdomyolysis, and non-specific gastrointestinal symptoms.
Direct effects will resolve within minutes of withdrawal of treatment.
11 DESCRIPTION
Vasopressin in Sodium Chloride Injection contains vasopressin, a polypeptide hormone. The chemical name of vasopressin is Cyclo (1-6) L-Cysteinyl-L-Tyrosyl-L-Phenylalanyl-L-Glutaminyl-L-Asparaginyl-L-Cysteinyl-L-Prolyl-L-Arginyl-L-Glycinamide. It is a white to off-white amorphous powder, freely soluble in water. The structural formula is:
Molecular Formula: C46H65N15O12S2 Molecular Weight: 1084.23
Vasopressin in Sodium Chloride Injection is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration. Each 100 mL contains 20 units (0.2 units/mL) or 40 units (0.4 units/mL) of vasopressin. Each 100mL also contains 900 mg Sodium Chloride, 33.6 mg Sodium DL-Lactate, and Water for Injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid. It has a pH of 3.6 – 4.0.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Vasopressin causes vasoconstriction by binding to V1 receptors on vascular smooth muscle coupled to the Gq/11-phospholipase C-phosphatidyl-inositol-triphosphate pathway, resulting in the release of intracellular calcium. In addition, vasopressin stimulates antidiuresis via stimulation of V2 receptors which are coupled to adenyl cyclase.
12.2 Pharmacodynamics
At therapeutic doses exogenous vasopressin elicits a vasoconstrictive effect in most vascular beds including the splanchnic, renal and cutaneous circulation. In addition, vasopressin at pressor doses triggers contractions of smooth muscles in the gastrointestinal tract mediated by muscular V1-receptors and release of prolactin and ACTH via V3 receptors. At lower concentrations typical for the antidiuretic hormone vasopressin inhibits water diuresis via renal V2 receptors. In addition, vasopressin has been demonstrated to cause vasodilation in numerous vascular beds that are mediated by V2, V3, oxytocin and purinergic P2 receptors.
In patients with vasodilatory shock vasopressin in therapeutic doses increases systemic vascular resistance and mean arterial blood pressure and reduces the dose requirements for norepinephrine. Vasopressin tends to decrease heart rate and cardiac output. The pressor effect is proportional to the infusion rate of exogenous vasopressin. The pressor effect reaches its peak within 15 minutes. After stopping the infusion the pressor effect fades within 20 minutes. There is no evidence for tachyphylaxis or tolerance to the pressor effect of vasopressin in patients.
12.3 Pharmacokinetics
Vasopressin plasma concentrations increase linearly with increasing infusion rates from 10 to 200 μU/kg/min. Steady state plasma concentrations are achieved after 30 minutes of continuous intravenous infusion.
Distribution
Vasopressin does not appear to bind plasma protein. The volume of distribution is 140 mL/kg.
Elimination
At infusion rates used in vasodilatory shock (0.01 to 0.1 units/minute), the clearance of vasopressin is 9 to 25 mL/min/kg in patients with vasodilatory shock. The apparent t1/2 of vasopressin at these levels is ≤10 minutes.
Metabolism
Serine protease, carboxipeptidase and disulfide oxido-reductase cleave vasopressin at sites relevant for the pharmacological activity of the hormone. Thus, the generated metabolites are not expected to retain important pharmacological activity.
Excretion
Vasopressin is predominantly metabolized and only about 6% of the dose is excreted unchanged into urine.
Specific Populations
- Pregnancy: Because of a spillover into blood of placental vasopressinase, the clearance of exogenous and endogenous vasopressin increases gradually over the course of a pregnancy. During the first trimester of pregnancy, the clearance is only slightly increased. However, by the third trimester the clearance of vasopressin is increased about 4-fold and at term up to 5-fold. After delivery, the clearance of vasopressin returns to pre-conception baseline within two weeks.
Drug Interaction Studies
- Indomethacin more than doubles the time to offset for vasopressin’s effect on peripheral vascular resistance and cardiac output in healthy subjects [see Drug Interactions (7.2)].
- The ganglionic blocking agent tetra-ethylammonium increases the pressor effect of vasopressin by 20% in healthy subjects [see Drug Interactions (7.3)].
- Halothane, morphine, fentanyl, alfentanyl and sufentanyl do not impact exposure to endogenous vasopressin.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No formal carcinogenicity or fertility studies with vasopressin have been conducted in animals. Vasopressin was found to be negative in the in vitro bacterial mutagenicity (Ames) test and the in vitro Chinese hamster ovary (CHO) cell chromosome aberration test. In mice, vasopressin has been reported to have an effect on function and fertilizing ability of spermatozoa.
14 CLINICAL STUDIES
Increases in systolic and mean blood pressure following administration of vasopressin were observed in 7 studies in septic shock and 8 in post-cardiotomy vasodilatory shock.
16 HOW SUPPLIED/STORAGE AND HANDLING
Vasopressin in Sodium Chloride Injection is supplied as a clear, practically colorless solution for intravenous administration in single-dose 100 mL ready-to-use containers available as:
|
Product Code |
Product Description |
NDC Number |
|
2G3498 |
20 units vasopressin (0.2 units/mL) Supplied as 12 bags per carton |
0338-9640-12 |
|
2G3499 |
40 units vasopressin (0.4 units/mL) Supplied as 12 bags per carton |
0338-9647-12 |
Store in the refrigerator (2°C to 8°C [36°F to 46°F]). Protect from freezing.
If needed, Vasopressin in Sodium Chloride Injection may be stored at room temperature up to 25°C (77°F) for up to 6 months. Discard after 6 months if stored at room temperature or until the expiration date printed on the carton and container label, whichever is earlier. Once stored at room temperature, do not place back in the refrigerator.
The drug product must be stored in its light protective carton during storage.
Manufactured by, Packed by, Distributed by:
Baxter Healthcare Corporation
Deerfield, IL 60015 USA
Printed in USA
07-19-06-884
Baxter and Galaxy are trademarks of Baxter International Inc.
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 0338-9640-12
Vasopressin
in 0.9% Sodium Chloride Injection
20 units per 100 mL (0.2 units/mL)
For Intravenous Infusion Only
100 mL Single-Dose Container
Discard Unused Portion
Rx only
Sterile
Each mL of the 0.2 units/mL strength also contains
9 mg sodium chloride, 0.336 mg sodium DL-lactate,
and water for injection. pH may have been adjusted
with sodium hydroxide or hydrochloric acid.
Dosage: See prescribing information.
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room
temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room
temperature.
Protect from light. Protect from freezing.
Do not add supplemental medication or additives.
Code 2G3498
BaxterLogo
Baxter Healthcare Corporation, Deerfield, IL 60015 USA
Product of USA
07-34-00-2001
BAR CODE
POSITION ONLY UPCA-A
XXXXXXXXXXXX
NDC 0338-9647-12
Vasopressin
in 0.9% Sodium Chloride Injection
40 units per 100 mL (0.4 units/mL)
For Intravenous Infusion Only
100 mL Single-Dose Container
Discard Unused Portion
Rx only
Sterile
Each mL of the 0.4 units/mL strength also contains
9 mg sodium chloride, 0.336 mg sodium DL-lactate,
and water for injection. pH may have been adjusted
with sodium hydroxide or hydrochloric acid.
Dosage: See prescribing information.
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room
temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room
temperature.
Protect from light. Protect from freezing.
Do not add supplemental medication or additives.
Code 2G3499
Baxter Logo
Baxter Healthcare Corporation, Deerfield, IL 60015 USA
Product of USA
07-34-00-2002
BAR CODE
POSITION ONLY UPCA-A
XXXXXXXXXXXX
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room temperature.
The drug product must be stored in its light protective carton during storage.
Protect from freezing.
Do not add supplemental medication or additives.
Vasopressin
in 0.9% Sodium Chloride Injection
20 units per 100 mL(0.2 units/mL)
Contains: 6 x 100 mL Single-Dose bags.
Each bag contains 100 mL.
BaxterLogo
Rx only
*FOR BAR CODE POSITION ONLY
(01) 00000000000000
(10)XX000000
(21) 000000000000
(17)00000000
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room temperature.
The drug product must be stored in its light protective carton during storage.
Protect from freezing.
Do not add supplemental medication or additives.
Vasopressin
in 0.9% Sodium Chloride Injection
20 units per 100 mL(0.2 units/mL)
Contains: 6 x 100 mL Single-Dose bags.
Each bag contains 100 mL.
BaxterLogo
Rx only
*FOR BAR CODE POSITION ONLY
(01) 00000000000000
(10)XX000000
(21) 000000000000
(17)00000000
NDC 0338-9640-12
Code 2G3498
*FOR BAR CODE POSITION ONLY
(01) XXXXXXXXXXXXXX
For Intravenous Infusion only
Each mL of the 0.2 units/mL strength also contains 9 mg sodium chloride, 0.336 mg sodium DL-lactate, and water
for injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.
Dosage: See prescribing information.
Baxter Healthcare Corporation,Deerfield, IL 60015 USA
07-04-00-1121
NDC 0338-9640-12
Code 2G3498
*FOR BAR CODE POSITION ONLY
(01) XXXXXXXXXXXXXX
For Intravenous Infusion only
Each mL of the 0.2 units/mL strength also contains 9 mg sodium chloride, 0.336 mg sodium DL-lactate, and water
for injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.
Dosage: See prescribing information.
Baxter Healthcare Corporation,Deerfield, IL 60015 USA
07-04-00-1121
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room temperature.
The drug product must be stored in its light protective carton during storage.
Protect from freezing.
Do not add supplemental medication or additives.
Vasopressin
in 0.9% Sodium Chloride Injection
40 units per 100 mL(0.4 units/mL)
Contains: 6 x 100 mL Single-Dose bags.
Each bag contains 100 mL.
BaxterLogo
Rx only
*FOR BAR CODE POSITION ONLY
(01) 00000000000000
(10)XX000000
(21) 000000000000
(17)00000000
Store refrigerated (2°C to 8°C [36°F to 46°F]).
If needed, product may be stored at room temperature up to 25°C (77°F) for up to 6 months.
Discard after 6 months if stored at room temperature.
The drug product must be stored in its light protective carton during storage.
Protect from freezing.
Do not add supplemental medication or additives.
Vasopressin
in 0.9% Sodium Chloride Injection
40 units per 100 mL(0.4 units/mL)
Contains: 6 x 100 mL Single-Dose bags.
Each bag contains 100 mL.
BaxterLogo
Rx only
*FOR BAR CODE POSITION ONLY
(01) 00000000000000
(10)XX000000
(21) 000000000000
(17)00000000
NDC 0338-9647-12
Code 2G3499
*FOR BAR CODE POSITION ONLY
(01) XXXXXXXXXXXXXX
For Intravenous Infusion only
Each mL of the 0.4 units/mL strength also contains 9 mg sodium chloride, 0.336 mg sodium DL-lactate, and water
for injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.
Dosage: See prescribing information.
Baxter Healthcare Corporation,Deerfield, IL 60015 USA
07-04-00-1122
NDC 0338-9647-12
Code 2G3499
*FOR BAR CODE POSITION ONLY
(01) XXXXXXXXXXXXXX
For Intravenous Infusion only
Each mL of the 0.4 units/mL strength also contains 9 mg sodium chloride, 0.336 mg sodium DL-lactate, and water
for injection. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.
Dosage: See prescribing information.
Baxter Healthcare Corporation,Deerfield, IL 60015 USA
07-04-00-1122