Dopamine Hydrochloride in Dextrose

1 INDICATIONS AND USAGE Dopamine Hydrochloride in Dextrose Injection is indicated to improve hemodynamic status in patients in distributive shock, or shock due to reduced cardiac output. Dopamine HCl in Dextrose Injection is a catecholamine indicated to improve hemodynamic status in patients in shock. ( 1 )

2 DOSAGE AND ADMINISTRATION • Correct hypovolemia, acidosis, and hypoxia prior to use. ( 2.1 ) • Administer in a large vein with an infusion pump preferably in an intensive care setting. ( 2.1 ) • Recommended starting dosage in adults and pediatric patients is 2 to 5 mcg/kg/minute as a continuous intravenous infusion. Titrate in 5 to 10 mcg/kg/minute increments based on hemodynamic response and tolerability, up to not more than 50 mcg/kg/minute. ( 2.2 ) • See the Full Prescribing Information for important preparation instructions and drug incompatibilities. ( 2.3 ) 2.1 Administration Instructions Correct Hypovolemia, Acidosis, and Hypoxia Address hypovolemia, acidosis, and hypoxia before initiating Dopamine HCl in Dextrose Injection. If patient does not respond to therapy, suspect occult hypovolemia. Acidosis may reduce the effectiveness of dopamine [see Warnings and Precautions (5.1) ] . Administration Dopamine HCl in Dextrose Injection is a premixed infusion solution that does not require dilution prior to intravenous administration. Administer Dopamine HCl in Dextrose Injection into a large vein [see Warnings and Precautions (5.1) ] with the use of an infusion pump preferably in an intensive care setting. Remove outer wrap (moisture and oxygen barrier) only when ready to administer the product. Discard product if outer wrap is damaged (e.g., tears or holes). Inspect Dopamine HCl in Dextrose Injection for particulate matter and discoloration prior to administration (the solution is clear to slightly yellow). Do not administer if the solution is darker than slightly yellow or the container is damaged. Use higher concentration premixed solutions (e.g., 3,200 mcg/mL or 1,600 mcg/mL strengths) in patients requiring fluid restriction. Discontinuation When discontinuing Dopamine HCl in Dextrose Injection, gradually reduce the infusion rate while expanding blood volume with intravenous fluids [see Warnings and Precautions (5.3) ]. 2.2 Recommended Dosage The recommended starting dosage in adults and pediatric patients is 2 to 5 mcg/kg/minute as a continuous intravenous infusion [see Dosage and Administration (2.3) ] . Titrate the infusion rate in 5 to 10 mcg/kg/minute increments based on hemodynamic response and tolerability, up to but not more than 50 mcg/kg/minute. Infusion rates may be calculated using the following formula: Infusion Rate (mL/hour) = [Dose (mcg/kg/minute) × Weight (kg) × 60 (minutes/hour)] Concentration (mcg/mL) Example calculations for infusion rates are as follows: Example 1: for a 60 kg person at the recommended initial dose of 2 mcg/kg/minute using a 1,600 mcg/mL concentration, the infusion rate would be as follows: Infusion Rate (mL/hour) = [2 (mcg/kg/minute) × 60 (kg) × 60 (minutes/hour) ] = 4.5 (mL/hour) 1,600 (mcg/mL) Example 2: for a 70 kg person at a dose of 5 mcg/kg/minute using a 3,200 mcg/mL concentration, the infusion rate would be as follows: Infusion Rate (mL/hour) = [5 (mcg/kg/minute) × 70 (kg) × 60 (minutes/hour) ] = 6.56 (mL/hour) 3,200 (mcg/mL) 2.3 Drug Incompatibilities Dopamine HCl in Dextrose Injection is incompatible with the following products; therefore, avoid simultaneous administration (through the same infusion set): • Sodium bicarbonate or other alkalinizing substances, because dopamine is inactivated in alkaline solution. • Blood, because of the risk of pseudoagglutination of red cells • Iron salts Do not add additional medications in the premixed infusion solution.

4 CONTRAINDICATIONS Dopamine is contraindicated in patients with pheochromocytoma. Patients with pheochromocytoma. ( 4 )

5 WARNINGS AND PRECAUTIONS • Tissue ischemia : Severe peripheral and visceral vasoconstriction can occur. Address hypovolemia prior to use, monitor extremities, and infuse into large vein. ( 5.1 ) • Cardiac arrhythmias : Monitor closely. ( 5.2 ) • Hypotension after abrupt discontinuation : Gradually reduce infusion rate while expanding blood volume with intravenous fluids. ( 5.3 ) • Severe hypersensitivity reactions due to sodium metabisulfite excipient : May cause anaphylaxis including life-threatening or less severe asthmatic episodes in susceptible individuals. ( 5.4 ) 5.1 Tissue Ischemia Administration of dopamine to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and hypouresis, tissue hypoxia, lactic acidosis, and poor systemic blood flow despite "normal" blood pressure. Address hypovolemia prior to initiating Dopamine HCl in Dextrose Injection [see Dosage and Administration (2.2) ] . Gangrene of the extremities has occurred in patients with occlusive vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of Dopamine HCl in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein [see Dosage and Administration (2.1) ] , check the infusion site frequently for free flow, and monitor for signs of extravasation. Emergency Treatment of Extravasation To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with: • 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults • 0.1 to 0.2 mg/kg of phentolamine mesylate up to a maximum of 10 mg per dose in pediatric patients. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.2 Cardiac Arrhythmias Dopamine may cause arrhythmias. Monitor patients with arrhythmias and treat appropriately. 5.3 Hypotension after Abrupt Discontinuation Sudden cessation of the infusion rate may result in marked hypotension. Gradually reduce the infusion rate while expanding blood volume with intravenous fluids. 5.4 Severe Hypersensitivity Reactions due to Sodium Metabisulfite Excipient Dopamine HCl in Dextrose Injection, contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

7 DRUG INTERACTIONS See Table 1 for clinically significant drug interactions with dopamine. Table 1: Clinically Significant Drug Interactions with Dopamine Halogenated Anesthetics Clinical Impact: Concomitant use may increase cardiac autonomic irritability and can sensitize the myocardium to the action of dopamine which may lead to ventricular arrhythmias and hypertension. Intervention: Monitor cardiac rhythm. Examples: desflurane, enflurane, isoflurane, and sevoflurane. MAO Inhibitors Clinical Impact: Because dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of dopamine which may result in severe hypertension and cardiac arrhythmia. Intervention: Reduce the recommended starting dosage to no greater than one-tenth (1/10) of the recommended dose in patients who have been treated with MAO inhibitors within two to three weeks prior to the administration of Dopamine HCl in Dextrose Injection. Examples: isocarboxazid, phenelzine, tranylcypromine, rasagiline, selegiline, linezolid. Tricyclic Antidepressants Clinical Impact: Concomitant use may potentiate the cardiovascular effects of dopamine (e.g., hypertension). Intervention: Monitor blood pressure. Examples: amitriptyline, desipramine, doxepin, imipramine, nortriptyline. Vasopressors Clinical Impact: Concomitant use may result in severe hypertension. Intervention: Monitor blood pressure. Examples: norepinephrine, epinephrine, oxytocin. • Halogenated anesthetics : Can sensitize the myocardium to the effects of dopamine and can produce ventricular arrhythmias and hypertension. ( 7 ) • MAO inhibitors : Risk of severe hypertension. Reduce recommended Dopamine HCl in Dextrose Injection dosage. ( 7 ) • Tricyclic antidepressants : Risk of hypertension. Monitor blood pressure. ( 7 ) • Vasopressors : Risk of severe hypertension. Monitor blood pressure. ( 7 )

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: • Tissue Ischemia [see Warnings and Precautions (5.1) ] • Cardiac Arrhythmias [see Warnings and Precautions (5.2) ] • Hypotension [see Warnings and Precautions (5.3) ] • Severe Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] The following adverse reactions have been identified during post-approval use of dopamine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders : anginal pain, palpitation Gastrointestinal Disorders : nausea, vomiting Metabolism and Nutrition Disorders : azotemia Nervous System Disorders : headache, anxiety Respiratory Disorders : dyspnea Skin and Subcutaneous Tissue Disorders : piloerection Vascular Disorders : hypertension The most common adverse reaction is localized vasoconstriction due to extravasation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Risk Summary There are no human data with dopamine use in pregnant women. There are risks to the mother and fetus from hypotension associated with shock, which can be fatal if left untreated ( see Clinical Considerations ). In animal reproduction studies, adverse developmental outcomes were observed with intravenous dopamine HCl administration in pregnant rats during organogenesis at dosages, on a mcg/m 2 basis, of one-third the human starting dosage of 2 mcg/kg/minute (90 mcg/m 2 /minute). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypotension associated with distributive shock, or shock due to reduced cardiac output are medical emergencies in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with distributive shock, or shock due to reduced cardiac output may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of dopamine on the fetus. Labor or Delivery Vasopressor drugs, including dopamine, may cause severe maternal hypertension when used concomitantly with some oxytocic drugs [see Drug Interactions (7) ] . Data Animal Data Animal reproduction studies in rats and rabbits at dopamine HCl dosages up to 6 mg/kg/day intravenously (on a mcg/m 2 basis, one-third and two-thirds, respectively, the human starting dosage of 2 mcg/kg/minute) during organogenesis produced no detectable teratogenic or embryotoxic effects, although maternal toxicity consisting of mortalities, decreased body weight gain, and pharmacotoxic signs were observed in rats. In a published study, administration of 10 mg/kg/day dopamine HCl (on a mcg/m 2 basis, two-thirds the human starting dosage of 2 mcg/kg/minute) to pregnant rats throughout gestation or for 5 days starting on gestation day 10 or 15 resulted in decreased body weight gain, increased mortality, and slight increase in cataract formation among the offspring.