Dopamine Hydrochloride

INDICATIONS AND USAGE Dopamine Hydrochloride, USP is indicated for the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure. Patients most likely to respond adequately to Dopamine Hydrochloride, USP are those in whom physiological parameters, such as urine flow, myocardial function, and blood pressure, have not undergone profound deterioration. Multiclinic trials indicate that the shorter the time interval between onset of signs and symptoms and initiation of therapy with blood volume correction and Dopamine Hydrochloride, USP, the better the prognosis. Where appropriate, blood volume restoration with a suitable plasma expander or whole blood should be accomplished prior to administration of Dopamine Hydrochloride, USP. Poor Perfusion of Vital Organs – Urine flow appears to be one of the better diagnostic signs by which adequacy of vital organ perfusion can be monitored. Nevertheless, the physician should also observe the patient for signs of reversal of confusion or reversal of comatose condition. Loss of pallor, increase in toe temperature, and/or adequacy of nail bed capillary filling may also be used as indices of adequate dosage. Clinical studies have shown that when Dopamine Hydrochloride, USP is administered before urine flow has diminished to levels of approximately 0.3 mL/minute, prognosis is more favorable. Nevertheless, in a number of oliguric or anuric patients, administration of Dopamine Hydrochloride, USP has resulted in an increase in urine flow, which in some cases reached normal levels. Dopamine Hydrochloride, USP may also increase urine flow in patients whose output is within normal limits and thus may be of value in reducing the degree of pre-existing fluid accumulation. It should be noted that at doses above those optimal for the individual patient, urine flow may decrease, necessitating reduction of dosage. Low Cardiac Output – Increased cardiac output is related to dopamine’s direct inotropic effect on the myocardium. Increased cardiac output at low or moderate doses appears to be related to a favorable prognosis. Increase in cardiac output has been associated with either static or decreased systemic vascular resistance (SVR). Static or decreased SVR associated with low or moderate movements in cardiac output is believed to be a reflection of differential effects on specific vascular beds with increased resistance in peripheral beds (e.g., femoral) and concomitant decreases in mesenteric and renal vascular beds. Redistribution of blood flow parallels these changes so that an increase in cardiac output is accompanied by an increase in mesenteric and renal blood flow. In many instances the renal fraction of the total cardiac output has been found to increase. Increase in cardiac output produced by dopamine is not associated with substantial decreases in systemic vascular resistance as may occur with isoproterenol. Hypotension – Hypotension due to inadequate cardiac output can be managed by administration of low to moderate doses of Dopamine Hydrochloride, USP which have little effect on SVR. At high therapeutic doses, dopamine’s alpha-adrenergic activity becomes more prominent and thus may correct hypotension due to diminished SVR. As in the case of other circulatory decompensation states, prognosis is better in patients whose blood pressure and urine flow have not undergone profound deterioration. Therefore, it is suggested that the physician administer Dopamine Hydrochloride, USP as soon as a definite trend toward decreased systolic and diastolic pressure becomes evident.

DOSAGE AND ADMINISTRATION WARNING: This is a potent drug; it must be diluted before administration to the patient. Dopamine hydrochloride injection is administered (only after dilution) by intravenous infusion. Suggested Dilution – For the 40 mg/mL preparation, transfer by aseptic technique the contents containing either 5 mL, 200 mg or 10 mL, 400 mg of dopamine hydrochloride to either a 250 mL or 500 mL bottle of one of the sterile I.V. solutions listed below. For the 80 mg/mL preparation, transfer by aseptic technique the contents containing 10 mL, 800 mg of dopamine hydrochloride to a 250 mL, 500 mL or 1000 mL bottle of one of the following sterile I.V. solutions: 0.9% Sodium Chloride Injection, USP 5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP 5% Dextrose and 0.45% Sodium Chloride Injection, USP 5% Dextrose and Lactated Ringer’s Injection Sodium Lactate Injection, USP 1/6 Molar Lactated Ringer’s Injection, USP The resultant dilutions are summarized in the following chart: Concentration of dopamine hydrochloride 40 mg/mL 80 mg/mL Volume of dopamine Hydrochloride Injection, USP 5 mL 10 mL 10 mL 250 mL Bottle of I.V. Solution 800 mcg/mL 1600 mcg/mL 3200 mcg/mL 500 mL Bottle of I.V. Solution 400 mcg/mL 800 mcg/mL 1600 mcg/mL 1000 mL Bottle of I.V. Solution 200 mcg/mL 400 mcg/mL 800 mcg/mL Dopamine hydrochloride injection has been found to be stable for a minimum of 24 hours after dilution in the foregoing I.V. solutions. However, as with all I.V. admixtures, dilution should be made just prior to administration. Do NOT add dopamine hydrochloride to Sodium Bicarbonate Injection, USP or other alkaline I.V. solutions, since the drug is inactivated in alkaline solution. Rate of Administration – Dopamine hydrochloride injection after dilution, is administered intravenously by infusion via a suitable I.V. catheter or needle. When administering dopamine hydrochloride (or any potent medication) by continuous intravenous infusion, it is advisable to use a precision volume control I.V. set. Each patient must be individually titrated to the desired hemodynamic or renal response to dopamine. In titrating to the desired increase in systolic blood pressure, the optimum dosage rate for renal response may be exceeded, thus necessitating a reduction in rate after the hemodynamic condition is stabilized. Administration at rates greater than 50 mcg/kg/min have safely been used in advanced circulatory decompensation states. If unnecessary fluid expansion is of concern, adjustment of drug concentration may be preferred over increasing the flow rate of a less concentrated dilution. Suggested Regimen: 1. When appropriate, increase blood volume with whole blood or plasma until central venous pressure is 10 to 15 cm H2O or pulmonary wedge pressure is 14 to 18 mm Hg. 2. Begin infusion of diluted solution at doses of 2 – 5 mcg/kg/min of dopamine hydrochloride in patients who are likely to respond to modest increments of heart force and renal perfusion. In more seriously ill patients, begin infusion of diluted solution at doses of 5 mcg/kg/min of dopamine hydrochloride and increase gradually using 5 to 10 mcg/kg/min increments up to a rate of 20 to 50 mcg/kg/min as needed. If doses in excess of 50 mcg/kg/min are required, it is advisable to check urine output frequently. Should urinary flow begin to decrease in the absence of hypotension, reduction of dopamine dosage should be considered. Multiclinic trials have shown that more than 50 percent of patients have been satisfactorily maintained on doses less than 20 mcg/kg/min. In patients who do not respond to these doses with adequate arterial pressures or urine flow, additional increments of dopamine may be given in an effort to produce an appropriate arterial pressure and central perfusion. 3. Treatment of all patients requires constant evaluation of therapy in terms of blood volume, augmentation of cardiac contractility, and distribution of peripheral perfusion. Dosage of dopamine should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indices for decreasing or temporarily suspending the dosage. 4. As with all potent intravenously administered drugs, care should be taken to control the rate of administration to avoid inadvertent administration of a bolus of the drug. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

ADVERSE REACTIONS The following adverse reactions have been observed, but there are not enough data to support an estimate of their frequency. Cardiovascular System: -ventricular arrhythmia -atrial fibrillation -ectopic beats -tachycardia -anginal pain -palpitation -cardiac conduction abnormalities -widened QRS complex -bradycardia -hypotension -hypertension -vasoconstriction Respiratory System: -dyspnea Gastrointestinal System: -nausea -vomiting Metabolic/Nutritional System: -azotemia Central Nervous System: -headache -anxiety Dermatological System: -piloerection Other: Gangrene of the extremities has occurred when high doses were administered for prolonged periods or in patients with occlusive vascular disease receiving low doses of dopamine HCl. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1‐877‐233‐2001 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.