DOPAMINE: 942 Adverse Event Reports & Safety Profile

DESCRIPTION Dopamine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution of Dopamine Hydrochloride, USP and Dextrose, USP in Water for Injection. Structural formulas are shown below: Dopamine Hydrochloride and 5% Dextrose Injection, USP is intended for intravenous use only. It contains no antimicrobial agents. The pH is adjusted with hydrochloric acid and is 3.5 (2.5 to 4.5).

Approximately

5 mEq/L sodium bisulfite is added as a stabilizer. The solution provides a caloric content of 170 kcal/L. The solution is intended for single use only. When smaller doses are required, the unused portion should be discarded. Composition and osmolarity are given below: 800 mcg/mL Dopamine Hydrochloride and 5% Dextrose Injection, USP provides 800 mcg/mL Dopamine Hydrochloride, USP and 50 g/L Dextrose Hydrous, USP with an osmolarity of 261 mOsmol/L (calc). 1600 mcg/mL Dopamine Hydrochloride and 5% Dextrose Injection, USP provides 1600 mcg/mL Dopamine Hydrochloride, USP and 50 g/L Dextrose Hydrous, USP with an osmolarity of 269 mOsmol/L (calc). 3200 mcg/mL Dopamine Hydrochloride and 5% Dextrose Injection, USP provides 3200 mcg/mL Dopamine Hydrochloride, USP and 50 g/L Dextrose Hydrous, USP with an osmolarity of 286 mOsmol/L (calc). Dopamine administered intravenously is a myocardial inotropic agent which also may increase mesenteric and renal blood flow plus urinary output. Dopamine hydrochloride is designated chemically as 3,4-dihydroxyphenethylamine hydrochloride, a white crystalline powder freely soluble in water. Dopamine (also referred to as 3-hydroxytyramine) is a naturally occurring biochemical catecholamine precursor of norepinephrine. This VIAFLEX Plus plastic container is fabricated from a specially formulated polyvinyl chloride (PL 2207 Plastic). VIAFLEX containers, including VIAFLEX Plus containers, are made of flexible plastic and are for parenteral use.

Viaflex

Plus on the container indicates the presence of a drug additive in a drug vehicle. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.

Dopamine

Hydrochloride, USP Structural Formula Image Dextrose Hydrous, USP (D-Gluocpyranose monohydrate)

Structural Formula

Image

INDICATIONS AND USAGE Dopamine hydrochloride is indicated for the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarctions, trauma, endotoxic septicemia, open heart surgery, renal failure and chronic cardiac decompensation as in congestive failure. Where appropriate, restoration of blood volume with a suitable plasma expander or whole blood should be instituted or completed prior to administration of dopamine hydrochloride. Patients most likely to respond adequately to dopamine hydrochloride are those in whom physiological parameters, such as urine flow, myocardial function and blood pressure have not undergone profound deterioration. Reports indicate that the shorter the time interval between onset of signs and symptoms and initiation of therapy with volume correction and dopamine hydrochloride, the better the prognosis.

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 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. Reported studies indicate that when dopamine hydrochloride 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 has resulted in an increase in urine flow which in some cases reached normal levels. Dopamine hydrochloride may also increase urine flow in patients whose output is within normal limits and thus may be of value in reducing the degree of preexisting fluid accumulation. It should be noted that at doses above those optimal for the individual patient, urine flow may decrease, necessitating reduction of dosage. Concurrent administration of dopamine hydrochloride and diuretic agents may produce an additive or potentiating effect.

Low Cardiac Output

Increased cardiac output is related to dopamine hydrochloride’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 increments 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 hydrochloride 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, which have little effect on SVR. At high therapeutic doses, dopamine hydrochloride’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 as soon as a definite trend toward decreased systolic and diastolic pressure becomes evident.

DOSAGE & ADMINISTRATION Do NOT administer if solution is darker than slightly yellow or discolored in any other way. Do NOT administer unless solution is clear and container is undamaged. Discard unused portion. Dextrose solutions without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility that pseudoagglutination of red cells may occur. Do NOT add sodium bicarbonate or other alkalinizing substance, since dopamine is inactivated in alkaline solution.

Dopamine

Hydrochloride in 5% Dextrose Injection should be infused into a large vein whenever possible to prevent the infiltration of perivascular tissue adjacent to the infusion site. Extravasation may cause necrosis and sloughing of the surrounding tissue. Large veins of the antecubital fossa are preferred to veins of the dorsum of the hand or ankle. Less suitable infusion sites should be used only when larger veins are unavailable and the patient's condition requires immediate attention. The physician should switch to a more suitable site as soon as possible and the infusion site in use should be continuously monitored for free flow. The less concentrated 800 mcg/mL solution may be preferred when fluid expansion is not a problem. The more concentrated 1600 mcg/mL or 3200 mcg/mL solutions, may be preferred in patients with fluid retention or when a slower rate of infusion is desired. Rate of Administration: Administration into an umbilical artery catheter is not recommended. Dopamine in 5% Dextrose Injection should not be infused through ordinary intravenous apparatus, regulated only by gravity and mechanical clamps. Only an infusion pump, preferably a volumetric pump, should be used. 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. If a disproportionate rise in diastolic pressure (i.e., a marked decrease in pulse pressure) is observed in patients receiving dopamine, the infusion rate should be decreased and the patient observed carefully for further evidence of predominant vasoconstrictor activity, unless such an effect is desired. Administration rates greater than 50 mcg/kg/min have safely been used in adults 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. When discontinuing the infusion, it may be necessary to gradually decrease the dose of dopamine HCl while expanding the blood volume with intravenous fluids to prevent the development of marked hypotension.

Suggested

Regimen: 1. When appropriate, increase blood volume with whole blood or plasma until central venous pressure is 10 to 15 cm H 2O or pulmonary wedge pressure is 14 to 18 mm Hg. 2. Begin infusion of dopamine hydrochloride solution at doses of 2 to 5 mcg/kg/min in adult or pediatric patients who are likely to respond to modest increments of heart force and renal perfusion. In more seriously ill patients, begin infusion of dopamine hydrochloride at doses of 5 mcg/kg/min 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, check urine output frequently. Should urinary flow begin to decrease in the absence of hypotension, reduction of dopamine dosage should be considered. More than 50% of adult 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, urine flow, cardiac output, blood pressure, and distribution of peripheral perfusion. Dosage of dopamine should be adjusted according to the patient's response. Diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias are reasons to consider decreasing or temporarily suspending the dosage. 4. As with all potent intravenously administered drugs, care should be taken to control the rate of infusion so as to avoid inadvertent administration of a bolus of the drug. 800 mcg/mL Dosing Chart for Dopamine (mL/hr)

Infusion Rate

1600 mcg/mL Dosing Chart for Dopamine (mL/hr)

Infusion Rate

3200 mcg/mL Dosing Chart for Dopamine (mL/hr)

Infusion Rate

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit. DOSAGE 1 DOSAGE 2 DOSAGE 3

CONTRAINDICATIONS Dopamine hydrochloride should not be used in patients with pheochromocytoma. Dopamine hydrochloride should not be administered in the presence of uncorrected tachyarrhythmias or ventricular fibrillation. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

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 postapproval 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 Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 &quot;normal&quot; blood pressure. Address hypovolemia prior to initiating Dopamine HCl in Dextrose Injection <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span> . 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> , 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.

PRECAUTIONS General Avoid bolus administration of dopamine hydrochloride. See DOSAGE AND ADMINISTRATION .

Avoid Hypovolemia

Prior to treatment with dopamine hydrochloride, hypovolemia should be fully corrected, if possible, with either whole blood, plasma, or plasma expanders as indicated. Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia. Hypoxia, Hypercapnia, Acidosis These conditions, which may also reduce the effectiveness and/or increase the incidence of adverse effects of dopamine, must be identified and corrected prior to, and concurrently with, administration of dopamine HCl.

Ventricular

Arrhythmias If an increased number of ectopic beats is observed, the dose should be reduced if possible.

Decreased Pulse

Pressure If a disproportionate rise in the diastolic pressure (i.e., marked decrease in the pulse pressure) is observed in patients receiving dopamine hydrochloride, the infusion rate should be decreased and the patient observed carefully for further evidence of predominant vasoconstrictor activity, unless such an effect is desired. Hypotension At lower infusion rates, if hypotension occurs, the infusion rate should be rapidly increased until adequate blood pressure is obtained. If hypotension persists, dopamine HCl should be discontinued and a more potent vasoconstrictor agent such as norepinephrine should be administered.

Occlusive Vascular Disease

Patients with a history of occlusive vascular disease (for example, atherosclerosis, arterial embolism, Raynaud’s disease, cold injury, diabetic endarteritis and Buerger’s disease) should be closely monitored for any changes in color or temperature of the skin in the extremities. If a change in skin color or temperature occurs and is thought to be the result of compromised circulation to the extremities, the benefits of continued dopamine hydrochloride infusion should be weighed against the risk of possible necrosis. This condition may be reversed by either decreasing the rate or discontinuing the infusion.

Extravasation Dopamine

Hydrochloride and 5% Dextrose Injection, USP should be infused into a large vein whenever possible to prevent the possibility of extravasation into tissue adjacent to the infusion site. Extravasation may cause necrosis and sloughing of surrounding tissue. Large veins of the antecubital fossa are preferred to veins in the dorsum of the hand or ankle. Less suitable infusion sites should be used only if the patient’s condition requires immediate attention. The physician should switch to more suitable sites as rapidly as possible. The infusion site should be continuously monitored for free flow. IMPORTANT - Antidote for Peripheral Ischemia To prevent sloughing and necrosis in ischemic areas, the area should be infiltrated as soon as possible with 10 to 15 mL of 0.9% Sodium Chloride Injection, USP containing from 5 to 10 mg phentolamine, an adrenergic blocking agent. A syringe with a fine hypodermic needle should be used and the solution liberally infiltrated throughout the ischemic area. Sympathetic blockage with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. Therefore, phentolamine should be given as soon as possible after the extravasation is noted.

Weaning

When discontinuing the infusion, it may be necessary to gradually decrease the dose of dopamine HCl while expanding blood volume with IV fluids, since sudden cessation may result in marked hypotension.

Careful Monitoring Required

Close monitoring of the following indices - urine flow, cardiac output and blood pressure - during dopamine hydrochloride infusion is necessary as in the case of any adrenergic agent. Solutions containing dextrose should be used with caution in patients with known subclinical or overt diabetes mellitus. Do not administer unless solution is clear and seal is intact. If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.

Laboratory Tests

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations and acid base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation.

Drug Interactions

Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and may sensitize the myocardium to the action of certain intravenously administered catecholamines, such as dopamine. This interaction appears to be related both to pressor activity and to the beta-adrenergic stimulating properties of these catecholamines, and may produce ventricular arrhythmias. Therefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics. Results of studies in animals indicate that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol. Because dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of dopamine. Patients who have been treated with MAO inhibitors within two to three weeks prior to the administration of dopamine should receive initial doses of dopamine hydrochloride no greater than one-tenth (1/10) of the usual dose. Concurrent administration of low-dose dopamine HCl and diuretic agents may produce an additive or potentiating effect on urine flow. Tricyclic antidepressants may potentiate the cardiovascular effects of adrenergic agents. Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents, such as propranolol and metoprolol. The peripheral vasoconstriction caused by high doses of dopamine HCl is antagonized by alpha-adrenergic blocking agents. Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha- or beta-adrenergic blocking agents. Butyrophenones (such as haloperidol) and phenothiazines can suppress the dopaminergic renal and mesenteric vasodilation induced with low-dose dopamine infusion. The concomitant use of vasopressors, vasoconstrictor agents (such as ergonovine) and some oxytocic drugs may result in severe hypertension. Administration of phenytoin to patients receiving dopamine HCl has been reported to lead to hypotension and bradycardia. It is suggested that in patients receiving dopamine HCl, alternatives to phenytoin should be considered if anticonvulsant therapy is needed. Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been performed to evaluate the carcinogenic potential of dopamine HCl. Dopamine HCl at doses approaching maximal solubility showed no clear genotoxic potential in the Ames test. Although there was a reproducible dose-dependent increase in the number of revertant colonies with strains TA100 and TA98, both with and without metabolic activation, the small increase was considered inconclusive evidence of mutagenicity. In the L5178Y TK ± mouse lymphoma assay, dopamine HCl at the highest concentrations used of 750 μg/ml without metabolic activation, and 3000 μg/ml with activation, was toxic and associated with increases in mutant frequencies when compared to untreated and solvent controls; at the lower concentrations no increases over controls were noted. No clear evidence of clastogenic potential was reported in the in vivo mouse or male rat bone marrow micronucleus test when the animals were treated intravenously with up to 224 mg/kg and 30 mg/kg of dopamine HCl, respectively.

Pregnancy Teratogenic Effects

Teratogenicity studies in rats and rabbits at dopamine HCl dosages up to 6 mg/kg/day intravenously 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, dopamine HCl administered at 10 mg/kg subcutaneously for 30 days, markedly prolonged metestrus and increased mean pituitary and ovary weights in female rats. Similar administration to pregnant rats throughout gestation or for 5 days starting on gestation day 10 or 15 resulted in decreased body weight gains, increased mortalities and slight increases in cataract formation among the offspring. There are no adequate and well-controlled studies in pregnant women, and it is not known if dopamine HCl crosses the placental barrier. Dopamine HCl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Labor and Delivery In obstetrics, if vasopressor drugs are used to correct hypotension or are added to a local anesthetic solution the interaction with some oxytocic drugs may cause severe hypertension.

Nursing

Mothers It is not known whether dopamine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dopamine hydrochloride is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established. The clearance of dopamine is affected by age (as much as 2 fold greater in children under 2 years of age), renal and hepatic function (decreasing by 2 fold in the presence of either). In younger children, particularly neonates, clearance is highly variable. Newborn infants may be more sensitive to the vasoconstrictive effects of dopamine. The most consistent effects of dopamine in 57 publications (between the years 1966 through 1997) were increases in systolic and mean arterial pressure. Renal function was variably affected, except that in a single publication renal function was preserved in the face of treatment with indomethacin. No consistent effect on heart rate was described. Because of the variability of clearance, especially in the neonate and newborn, low doses of dopamine and slow deliberate titration should be employed (see DOSAGE and ADMINISTRATION ).

Geriatric Use

Clinical studies of dopamine injection 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.

Drug Interactions Because dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of dopamine. Patients who have been treated with MAO inhibitors within two to three weeks prior to the administration of dopamine HCl should receive initial doses of dopamine HCl no greater than one-tenth (1/10) of the usual dose. Concurrent administration of dopamine HCl and diuretic agents may produce an additive or potentiating effect on urine flow. Tricyclic antidepressants may potentiate the pressor response to adrenergic agents. Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents , such as propranolol and metoprolol. The peripheral vasoconstriction caused by high doses of dopamine HCl is antagonized by alpha-adrenergic blocking agents . Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha- or beta-adrenergic blocking agents. Haloperidol appears to have strong central antidopaminergic properties. Haloperidol and haloperidol-like drugs suppress the dopaminergic renal and mesenteric vasodilation induced at low rates of dopamine infusion. Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and may sensitize the myocardium to the action of certain intravenously administered catecholamines, such as dopamine. This interaction appears to be related both to pressor activity and to beta-adrenergic stimulating properties of these catecholamines and may produce ventricular arrhythmias and hypertension. Therefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics. It has been reported that results of studies in animals indicate that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol. The concomitant use of vasopressors and some oxytocic drugs may result in severe persistent hypertension.

See

Labor and Delivery below. Administration of phenytoin to patients receiving dopamine HCl has been reported to lead to hypotension and bradycardia. It is suggested that in patients receiving dopamine HCl, alternatives to phenytoin should be used if anticonvulsant therapy is needed. Pregnancy: Teratogenic Effects: Animal studies have revealed no evidence of teratogenic effects due to dopamine. However, in one study, administration of dopamine HCl to pregnant rats resulted in a decreased survival rate of the newborn and a potential for cataract formation in the survivors. There are no adequate and well-controlled studies in pregnant women and it is not known if dopamine crosses the placental barrier. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if, in the judgment of the physician, the potential benefit justifies the potential risk to the fetus.

ACTIVE INGREDIENTS: Dopamine Hydrochloride 8X, 12X, 30X, 12C, 30C, Hydrastis Canadensis 6X, L-Dopa 8X, 12X, 30X, 12C, 30C, Melatonin 6X, 12X, 30X, 12C, 30C, Serotonin (Hydrochloride) 8X, 12X, 30X, 12C, 30C, Taraxacum Officinale 3X.

INACTIVE INGREDIENT SECTION Inactive Ingredients: USP Purified Water; USP Gluten-free, non-GMO, organic cane alcohol 20%.