Vasopressin

Vasostrict ® is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Vasostrict ® is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. ( 1 )

Injection: vasopressin injection, USP is a clear, practically colorless solution available as: 20 units/mL in a single dose vial. To be used after dilution. 200 units/10 mL (20 units/mL) in a multiple dose vial. To be used after dilution. 20 units/100 mL (0.2 units/mL) premixed in dextrose in a single dose vial. Ready to use. 40 units/100 mL (0.4 units/mL) premixed in dextrose in a single dose vial. Ready to use. 60 units/100 mL (0.6 units/mL) premixed in dextrose in a single dose vial. Ready to use. 50 units/50 mL (1 unit/mL) premixed in dextrose in a single dose vial. Ready to use. Injection: 20 units/mL in a single dose vial. To be used after dilution. 200 units/10 mL (20 units/mL) in a multiple dose vial. To be used after dilution. 20 units/100 mL (0.2 units/mL) premixed in dextrose in a single dose vial. Ready to use. 40 units/100 mL (0.4 units/mL) premixed in dextrose in a single dose vial. Ready to use. 60 units/100 mL (0.6 units/mL) premixed in dextrose in a single dose vial. Ready to use. 50 units/50 mL (1 unit/mL) premixed in dextrose in a single dose vial. Ready to use.

Vasostrict ® 10 mL multiple dose vial is contraindicated in patients with known allergy or hypersensitivity to 8‑L-arginine vasopressin or chlorobutanol. The 1 mL single dose vial, 50 mL and 100 mL pre-mixed single dose vial does not contain chlorobutanol and is therefore contraindicated only in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. Vasostrict ® 10 mL multiple dose vial is contraindicated in patients with known allergy or hypersensitivity to 8‑L-arginine vasopressin or chlorobutanol. The 1 mL single dose vial, 50 mL and 100 mL pre-mixed single dose vial does not contain chlorobutanol and is therefore contraindicated only in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. (4)

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

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.

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 Postmarketing Experience Reversible diabetes insipidus [see Warnings and Precautions (5.2) ] The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia and ischemia (coronary, mesenteric, skin, digital). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pressor effects of catecholamines and Vasostrict ® are expected to be additive. ( 7.1 ) Indomethacin may prolong effects of Vasostrict ® . ( 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 )

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 Vasostrict ® 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 Vasostrict ® 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 Vasostrict ® . 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 Vasostrict ® . Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

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 )

8.1 Pregnancy Risk Summary There are no available data on Vasostrict ® 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 with vasopressin . 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 Vasostrict ® may need to be increased [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] . Maternal adverse reactions: Vasostrict ® 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 Vasostrict ® 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) ] .

Vasopressin causes vasoconstriction by binding to V 1 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 V 2 receptors which are coupled to adenyl cyclase.