These Highlights Do Not Include All The Information Needed To Use Vasopressin In Sodium Chloride Injection Safely And Effectively. See Full Prescribing Information For Vasopressin In Sodium Chloride Injection.

Postmarketing Experience

Reversible diabetes insipidus [see Warnings and Precautions (5.2)]

Principal Display Panel – 20 Units per 100 mL Carton Label

Vasopressin

in 0.9% Sodium Chloride Injection

20 Units per 100 mL (0.2 units per mL)

For intravenous infusion

Ready to use

10 x 100 mL Single-Dose Vials

Discard Unused Portion

NDC 81298-8552-3

Rx only

Recommended Dosage: See

Prescribing Information.

LONG GROVE™

PHARMACEUTICALS

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.

There are no data on the presence of Vasopressin in Sodium Chloride Injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

Vasopressin is a polypeptide hormone. Vasopressin in Sodium Chloride Injection is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration.

Each mL of the 0.2 unit/mL strength contains 0.2 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.05 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 0.4 unit/mL strength contains 0.4 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.10 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 1 unit/mL strength contains 1 unit vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.25 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP.

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

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)].

Safety and effectiveness of Vasopressin in Sodium Chloride Injection in pediatric patients with vasodilatory shock have not been established.

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)].

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 postcardiotomy 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 in Sodium Chloride Injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

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.

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.

Vasopressin in Sodium Chloride Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

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 their frequency reliably or to 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

• Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. (7.1)
• Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. (7.2)
• Co-administration of ganglionic blockers or drugs causing SIADH may increase the pressor response. (7.3, 7.4)
• Co-administration of drugs causing diabetes insipidus may decrease the pressor response. (7.5)

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.

Vasopressin plasma concentrations increase linearly with increasing infusion rates from 10 micro-units/kg/min to 200 micro-units /kg/min. Steady state plasma concentrations are achieved after 30 minutes of continuous intravenous infusion.

Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

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.

• Can worsen cardiac function. (5.1)
• Reversible diabetes insipidus (5.2)

• This product does not require further dilution prior to administration. (2.1)
• Post-cardiotomy shock: 0.03 units/minute to 0.1 units/minute by intravenous infusion (2.2)
• Septic shock: 0.01 units/minute to 0.07 units/minute by intravenous infusion (2.2)

Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit.

This product does not require further dilution prior to administration.

Vasopressin in Sodium Chloride Injection is a clear, colorless premixed solution for intravenous administration in a single-dose, ready to use vial available as:

• 20 units/100 mL (0.2 units/mL) in 0.9% Sodium Chloride
• 40 units/100 mL (0.4 units/mL) in 0.9% Sodium Chloride
• 50 units/50 mL (1 unit/mL) in 0.9% Sodium Chloride

• Pregnancy: May induce uterine contractions. (8.1)
• Pediatric Use: Safety and effectiveness have not been established. (8.4)
• Geriatric Use: No safety issues have been identified in older patients. (8.5)

A decrease in cardiac index may be observed with the use of vasopressin.

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)].

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.

Vasopressin in Sodium Chloride Injection is a clear, colorless solution for intravenous administration available as:

NDC 81298-8552-3: A carton of 10 single dose vials. Each vial contains vasopressin 20 units/100 mL (0.2 units/mL).

NDC 81298-8554-3: A carton of 10 single dose vials. Each vial contains vasopressin 40 units/100 mL (0.4 units/mL).

NDC 81298-8550-3: A carton of 10 single dose vials. Each vial contains vasopressin 50 units/50 mL (1 unit/mL).

Store unopened vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep vials in original carton to protect from light.

Vials may be held up to three (3) months upon removal from refrigeration to room temperature storage conditions (20°C to 25°C [68°F to 77°F], USP Controlled Room Temperature), anytime within the labeled shelf life. Once removed from refrigeration, unopened vial should be marked to indicate the revised three (3) months expiration date. If the manufacturer's original expiration date is shorter than the revised expiration date, then the shorter date must be used. Do not use Vasopressin in Sodium Chloride Injection beyond the manufacturer's expiration date stamped on the vial.

Manufactured for:

Long Grove Pharmaceuticals, LLC

Rosemont, IL 60018

Made in India

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.

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.

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.

Postmarketing Experience

Reversible diabetes insipidus [see Warnings and Precautions (5.2)]

Principal Display Panel – 20 Units per 100 mL Carton Label

Vasopressin

in 0.9% Sodium Chloride Injection

20 Units per 100 mL (0.2 units per mL)

For intravenous infusion

Ready to use

10 x 100 mL Single-Dose Vials

Discard Unused Portion

NDC 81298-8552-3

Rx only

Recommended Dosage: See

Prescribing Information.

LONG GROVE™

PHARMACEUTICALS

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.

There are no data on the presence of Vasopressin in Sodium Chloride Injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

Vasopressin is a polypeptide hormone. Vasopressin in Sodium Chloride Injection is a sterile, aqueous solution of synthetic arginine vasopressin for intravenous administration.

Each mL of the 0.2 unit/mL strength contains 0.2 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.05 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 0.4 unit/mL strength contains 0.4 units vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.10 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP. Each mL of the 1 unit/mL strength contains 1 unit vasopressin, 0.0672 mg aspartic acid, 0.0180 mg boric acid, 0.25 mg chlorobutanol, 9 mg sodium chloride and Water for Injection, USP.

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

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)].

Safety and effectiveness of Vasopressin in Sodium Chloride Injection in pediatric patients with vasodilatory shock have not been established.

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)].

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 postcardiotomy 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 in Sodium Chloride Injection by 0.005 units/minute every hour as tolerated to maintain target blood pressure.

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.

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.

Vasopressin in Sodium Chloride Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

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 their frequency reliably or to 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

• Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. (7.1)
• Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. (7.2)
• Co-administration of ganglionic blockers or drugs causing SIADH may increase the pressor response. (7.3, 7.4)
• Co-administration of drugs causing diabetes insipidus may decrease the pressor response. (7.5)

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.

Vasopressin plasma concentrations increase linearly with increasing infusion rates from 10 micro-units/kg/min to 200 micro-units /kg/min. Steady state plasma concentrations are achieved after 30 minutes of continuous intravenous infusion.

Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

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.

• Can worsen cardiac function. (5.1)
• Reversible diabetes insipidus (5.2)

• This product does not require further dilution prior to administration. (2.1)
• Post-cardiotomy shock: 0.03 units/minute to 0.1 units/minute by intravenous infusion (2.2)
• Septic shock: 0.01 units/minute to 0.07 units/minute by intravenous infusion (2.2)

Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit.

This product does not require further dilution prior to administration.

Vasopressin in Sodium Chloride Injection is a clear, colorless premixed solution for intravenous administration in a single-dose, ready to use vial available as:

• 20 units/100 mL (0.2 units/mL) in 0.9% Sodium Chloride
• 40 units/100 mL (0.4 units/mL) in 0.9% Sodium Chloride
• 50 units/50 mL (1 unit/mL) in 0.9% Sodium Chloride

• Pregnancy: May induce uterine contractions. (8.1)
• Pediatric Use: Safety and effectiveness have not been established. (8.4)
• Geriatric Use: No safety issues have been identified in older patients. (8.5)

A decrease in cardiac index may be observed with the use of vasopressin.

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)].

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.

Vasopressin in Sodium Chloride Injection is a clear, colorless solution for intravenous administration available as:

NDC 81298-8552-3: A carton of 10 single dose vials. Each vial contains vasopressin 20 units/100 mL (0.2 units/mL).

NDC 81298-8554-3: A carton of 10 single dose vials. Each vial contains vasopressin 40 units/100 mL (0.4 units/mL).

NDC 81298-8550-3: A carton of 10 single dose vials. Each vial contains vasopressin 50 units/50 mL (1 unit/mL).

Store unopened vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep vials in original carton to protect from light.

Vials may be held up to three (3) months upon removal from refrigeration to room temperature storage conditions (20°C to 25°C [68°F to 77°F], USP Controlled Room Temperature), anytime within the labeled shelf life. Once removed from refrigeration, unopened vial should be marked to indicate the revised three (3) months expiration date. If the manufacturer's original expiration date is shorter than the revised expiration date, then the shorter date must be used. Do not use Vasopressin in Sodium Chloride Injection beyond the manufacturer's expiration date stamped on the vial.

Manufactured for:

Long Grove Pharmaceuticals, LLC

Rosemont, IL 60018

Made in India

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.

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.

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.