High Alert Ready-to-Use Premix Medications

Dexmedetomidine Hydrochloride in 0.9% Sodium Chloride Injection

200 mcg/50 mL (4 mcg/mL) in a 50 mL Galaxy container

400 mcg/100 mL (4 mcg/mL) in a 100 mL Galaxy container

Indications and Important Risk Information

Indications

Dexmedetomidine hydrochloride in 0.9% sodium chloride injection is an alpha₂-adrenergic receptor agonist indicated for:

• Sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. Administer dexmedetomidine hydrochloride in 0.9% sodium chloride injection by continuous infusion not to exceed 24 hours.
• Sedation of non-intubated adult patients prior to and/or during surgical and other procedures.

Important Risk Information

• Contraindications: None
• Monitoring: Dexmedetomidine hydrochloride in 0.9% sodium chloride injection should be administered only by persons skilled in the management of patients in the intensive care or operating room setting. Patients should be continuously monitored.
• Hypotension, Bradycardia, and Sinus Arrest: Clinically significant episodes of bradycardia and sinus arrest have been reported with administration in young, healthy adult volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration.
  Reports of hypotension and bradycardia have been associated with dexmedetomidine hydrochloride in 0.9% sodium chloride injection infusion. Some of these cases have resulted in fatalities. If medical intervention is required, treatment may include decreasing or stopping the infusion, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents.
  Caution should be exercised when administering to patients with advanced heart block and/or severe ventricular dysfunction. Hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension and in elderly patients.
  Use with caution with co-administration with other vasodilators or negative chronotropic agents.
• Transient Hypertension: Has been observed primarily during the loading dose. Treatment has generally not been necessary, although reduction of the loading infusion rate may be desirable.
• Arousability: Some patients have been observed to be arousable and alert when stimulated. This alone should not be considered as evidence of lack of efficacy in the absence of other clinical signs and symptoms.
• Tolerance and Tachyphylaxis: Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions.
• Hyperthermia or Pyrexia: May be resistant to traditional cooling methods, such as administration of cooled intravenous fluids and antipyretic medications. Discontinue if drug-related hyperthermia or pyrexia is suspected and monitor patients until body temperature normalizes.
• Hepatic Impairment: Clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function.
• Adverse Reactions:
  •  The most common adverse reactions (incidence >2%) in adults are hypotension, bradycardia, and dry mouth.
  • Adverse reactions in adults, associated with infusions >24 hours in duration include ARDS, respiratory failure, and agitation.
• Drug Interactions:
  • Anesthetics, Sedatives, Hypnotics, Opioids: Enhancement of pharmacodynamic effects. Reduction in dosage of dexmedetomidine hydrochloride in 0.9% sodium chloride injection or the concomitant medication may be required.

Please see accompanying full Prescribing Information for Dexmedetomidine Hydrochloride in 0.9% Sodium Chloride Injection.

Dobutamine Hydrochloride in 5% Dextrose Injection

250 mg/250 mL, 500 mg/250 mL, 1000 mg/250 mL

Indications and Important Risk Information

Indications

Dobutamine Hydrochloride in 5% Dextrose Injection is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures. Experience with intravenous dobutamine in controlled trials does not extend beyond 48 hours of repeated boluses and/or continuous infusions.
Whether given orally, continuously intravenously, or intermittently intravenously, neither dobutamine nor any other cyclic-AMP-dependent inotrope has been shown in controlled trials to be safe or effective in the long-term treatment of congestive heart failure.

Important Risk Information

Contraindications

Dobutamine Hydrochloride in 5% Dextrose Injection is contraindicated in patients with idiopathic hypertrophic subaortic stenosis and in patients who have shown previous manifestations of hypersensitivity to dobutamine.
Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Warnings and Precautions

• Increase in Heart Rate or Blood Pressure: Dobutamine Hydrochloride in 5% Dextrose Injection may cause a marked increase in heart rate or blood pressure, especially systolic pressure. Usually, reduction of dosage reverses these effects. Because dobutamine facilitates atrioventricular conduction, patients with atrial fibrillation are at risk of developing rapid ventricular response. Patients with preexisting hypertension appear to face an increased risk of developing an exaggerated pressor response. In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to institution of therapy with Dobutamine in D5W.
• Ectopic Activity: Dobutamine Hydrochloride in 5% Dextrose Injection may precipitate or exacerbate ventricular ectopic activity, but it rarely has caused ventricular tachycardia.
• Hypersensitivity: Reactions suggestive of hypersensitivity associated with administration of dobutamine including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally. Dobutamine Hydrochloride in 5% Dextrose Injection contains sodium bisulfite, 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.
• General: During the administration of Dobutamine Hydrochloride in 5% Dextrose Injection, as with any adrenergic agent, ECG and blood pressure should be continuously monitored. In addition, pulmonary wedge pressure and cardiac output should be monitored whenever possible to aid in the safe and effective infusion of dobutamine.
  Hypovolemia should be corrected with suitable volume expanders before treatment with dobutamine is instituted. No improvement may be observed in the presence of marked mechanical obstruction, such as severe valvular aortic stenosis.
• Adverse Reactions:
• Hypotension: Precipitous decreases in blood pressure have occasionally been described in association with dobutamine therapy. Decreasing the dose or discontinuing the infusion typically results in rapid return of blood pressure to baseline values. In rare cases, however, intervention may be required and reversibility may not be immediate.
• Stress Cardiomyopathy: Stress cardiomyopathy has been reported with dobutamine in association with cardiac stress testing.
• Reactions at Sites of Intravenous Infusion: Phlebitis has occasionally been reported. Local inflammatory changes have been described following inadvertent infiltration.
• The following adverse effects have been reported in 1% to 3% of adult patients: nausea, headache, anginal pain, nonspecific chest pain, palpitations, and shortness of breath.
• Drug Interactions: There was no evidence of drug interactions in clinical studies in which dobutamine was administered concurrently with other drugs, including digitalis preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and acetaminophen. Preliminary studies indicate that the concomitant use of dobutamine and nitroprusside results in a higher cardiac output and, usually, a lower pulmonary wedge pressure than when either drug is used alone.

Please see accompanying full Prescribing Information for Dobutamine Hydrochloride in 5% Dextrose Injection.

Dopamine Hydrochloride and 5% Dextrose Injection, USP

800 mcg/mL in 250 mL; 1600 mcg/mL in 250 mL; 800 mcg/mL in 500 mL; 3200 mcg/mL in 250 mL; 1600 mcg/mL in 500 mL

Indications and Important Risk Information

Indications

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.

Important Risk Information

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.

Warnings and Precautions

• Evidence is inadequate for fully defining proper dosage and limitations for use in children.
• Contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.
• Do not add Dopamine Hydrochloride and 5% Dextrose Injection, USP to any alkaline diluent solution since dopamine hydrochloride is inactivated in alkaline solution.
• Avoid bolus administration of dopamine hydrochloride.
• 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 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.
• Adverse Reactions: The following adverse reactions have been observed, but there are not enough data to support an estimate of their frequency: ventricular arrhythmia, atrial fibrillation, ectopic beats, tachycardia, anginal pain, palpitation, cardiac conduction abnormalities, widened QRS complex, bradycardia, hypotension, hypertension, vasoconstriction, dyspnea, nausea, vomiting, azotemia, headache, anxiety, piloerection, gangrene of the extremities.
• 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 may produce ventricular arrhythmias. Therefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics.
• 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.
• 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 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.

Please see accompanying full Prescribing Information for Dopamine Hydrochloride and 5% Dextrose Injection, USP.

Lidocaine Hydrochloride and 5% Dextrose Injection, USP

2 grams/250 mL (8 mg/mL) and 2 grams/500 mL (4 mg/mL)

Indications and Important Risk Information

Indications

Lidocaine hydrochloride administered intravenously is specifically indicated in the acute management of:

1. ventricular arrhythmias occurring during cardiac manipulations, such as cardiac surgery

2. life-threatening arrhythmias which are ventricular in origin, such as occur during acute myocardial infarction

Important Risk Information

Contraindications

Hypersensitivity reactions, including anaphylactic reactions, have been reported with lidocaine. Lidocaine hydrochloride is contraindicated in patients with a history of hypersensitivity to local anesthetics of the amide type.
Lidocaine is contraindicated in patients with Stokes-Adams syndrome, Wolff-Parkinson- White syndrome, or with severe degrees of sinoatrial, atrioventricular, or intraventricular block.

Warnings and Precautions

• Monitoring: Constant monitoring with an electrocardiograph is essential to the administration of lidocaine hydrochloride intravenously. Signs of excessive depression of cardiac conductivity, such as prolongation of the PR interval, widening of the QRS interval and the appearance or aggravation of arrhythmias, should be followed by prompt cessation of the intravenous infusion of this agent. It is mandatory to have emergency resuscitative equipment and drugs immediately available to manage adverse reactions involving cardiovascular, respiratory, or central nervous systems. Central nervous system adverse reactions are associated with venous plasma levels above 6.0 μg free base per mL.
• Hypersensitivity: Hypersensitivity, including anaphylaxis, has been reported with lidocaine-containing solutions. Stop the infusion immediately if signs of hypersensitivity develop.
• Atrial Fibrillation or Flutter: Acceleration of ventricular rate may occur in patients with atrial fibrillation or flutter treated with lidocaine.
• Sinus bradycardia or incomplete heart block: In patients with sinus bradycardia or incomplete heart block, the administration of lidocaine hydrochloride intravenously for the elimination of ventricular ectopic beats without prior acceleration in heart rate (e.g., by isoproterenol or by electric pacing) may promote more frequent and serious ventricular arrhythmias or complete heart block.
• Renal or hepatic insufficiency: Because lidocaine is metabolized mainly in the liver and excreted by the kidneys, patients with renal or hepatic insufficiency may be at increased risk for toxicity.
• Malignant Hyperthermia: If malignant hyperthermia develops, discontinue administration immediately and institute therapeutic countermeasures as clinically indicated.
• Adverse Reactions: Systemic reactions of the following types have been reported:
  Nervous System Disorders: respiratory depression and arrest; unconsciousness; convulsions; tremors; twitching; vomiting; blurred or double vision; drowsiness; dizziness; light-headedness; tinnitus; sensation of heat, cold or numbness; euphoria; apprehension; agitation; confused state; paresthesia; dysarthria.
  Cardiovascular System: cardiovascular arrest; bradycardia which may lead to cardiac arrest; hypotension, Ventricular fibrillation, Ventricular tachycardia, Ventricular arrhythmia, Asystole.
  Gastrointestinal Disorders: Hypoesthesia oral, Nausea.
  Hematologic Effects: methemoglobinemia.
  Psychiatric Disorders: Disorientation.
• Drug Interactions:
• Pharmacodynamic Interactions:
• Digitalis derivatives: Monitor toxicity when lidocaine is used in patients with digitalis toxicity accompanied by supraventricular arrhythmia and/or atrioventricular block.
• When lidocaine is administered with other antiarrhythmic drugs such as amiodarone, phenytoin, procainamide, propranolol or quinidine, the cardiac effects may be additive or antagonistic and toxic effects may be additive.
• Pharmacokinetic Interactions:
• Concomitant treatment with drugs which are inhibitors of CYP1A2 and/or CYP3A4 has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and thereby prolonging the elimination half-life. Monitor toxicity when administering lidocaine with CYP1A2 and/or CYP3A4 inhibitors.
• Concomitant use of lidocaine at steady-state concentrations of the CYP1A2 inhibitor fluvoxamine increases intravenous lidocaine plasma AUC and Cmax and decreases MEGX AUC and Cmax. Monitor toxicity when co-administering these medications.
• Concomitant use of lidocaine with propofol, a hypnotic agent and CYP3A4 inhibitor, may increase lidocaine plasma levels by reducing lidocaine clearance. Monitor toxicity when co-administering lidocaine with propofol.
• Concomitant treatment with drugs which are inducers of CYP1A2 and/or CYP3A4 (e.g., phenytoin) has the potential to decrease lidocaine plasma levels and higher doses may be required.
• Concomitant use of lidocaine with a weak CYP1A2 and CYP3A4 inhibitor has been reported to increase lidocaine plasma levels and may result in toxic accumulation of the drug. Monitor toxicity when co-administering lidocaine with cimetidine.
• Beta-adrenergic blockers (e.g. propranolol): Concomitant use of lidocaine with beta-adrenergic blockers may increase lidocaine plasma levels by decreasing hepatic blood flow and thereby decrease lidocaine clearance. Monitor for toxicity when co-administering lidocaine with drugs that decrease hepatic blood flow.

Please see accompanying full Prescribing Information for Lidocaine Hydrochloride and 5% Dextrose Injection, USP.

Magnesium Sulfate in 5% Dextrose Injection, USP

1g/100 mL

Indications and Important Risk Information

Indications

Magnesium Sulfate in 5% Dextrose Injection is indicated for:

• Prevention of eclampsia in patients with preeclampsia

• Treatment of seizures and prevention of recurrent seizures in patients with eclampsia

Important Risk Information

Contraindications

Magnesium Sulfate in 5% Dextrose Injection is contraindicated in patients:

• with heart block or myocardial damage

• in diabetic coma

• with myasthenia gravis

Warnings and Precautions

• Fetal-Neonatal Toxicity with Prolonged Use: Continuous administration of magnesium sulfate beyond 5 to 7 days in pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus, including skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. Neonates of women receiving Magnesium Sulfate in 5% Dextrose Injection (especially with prolonged maternal use) are at risk for magnesium toxicity including hyporeflexia, hypotonia, and respiratory depression. There is one reported case of neonatal death as the result of magnesium toxicity after transplacental exposure. The shortest duration of magnesium sulfate treatment that can lead to fetal harm is not known.
• Risk of Magnesium Toxicity: Patients receiving Magnesium Sulfate in 5% Dextrose Injection are at risk for magnesium toxicity including respiratory depression, acute renal failure, and rarely, pulmonary edema. Monitor clinical signs of magnesium toxicity (for example, facial edema, diminished strength of deep tendon reflexes, respiratory depression) and magnesium concentrations during infusions. An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium toxicity in patients with preeclampsia and eclampsia. If there is significant magnesium toxicity, stop the Magnesium Sulfate in 5% Dextrose Injection infusion and recheck serum magnesium concentration. Patients with renal impairment are at greater risk of magnesium toxicity because magnesium is excreted by the body solely by the kidneys. Urine output should be maintained at a level of 100 mL per 4 hours.
• Risk of Elevated Blood Glucose: Solutions containing dextrose should be used with caution in patients with known prediabetes or diabetes mellitus given the risk of elevated blood glucose.
• Co-administration with Unapproved Tocolytics: Do not use Magnesium Sulfate in 5% Dextrose Injection with unapproved tocolytics (e.g., beta-adrenergic agents such as terbutaline, or calcium channel blockers such as nifedipine). Serious adverse events including pulmonary edema and hypotension have occurred.
• Aluminum Toxicity: Magnesium Sulfate in 5% Dextrose Injection contains aluminum that may be toxic. Aluminum may reach toxic concentrations with prolonged parenteral administration in patients with renal impairment. Patients with renal impairment who receive parenteral concentrations of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at concentrations associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
• Exacerbation of Myasthenia Gravis: Use of magnesium sulfate in patients with underlying myasthenia gravis can precipitate a myasthenic crisis. Myasthenic crisis is a life-threatening condition characterized by neuromuscular respiratory failure. Symptoms of myasthenic crisis may include difficulty swallowing, ptosis, facial droop, weakness, and/or difficulty breathing that may require intubation. If myasthenic crisis is suspected, discontinue use of Magnesium Sulfate in 5% Dextrose Injection immediately. Secure the patient’s airway.
• Adverse Reactions: The most common adverse reactions are flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system (CNS) depression proceeding to respiratory paralysis, and hypocalcemia.
• Drug Interactions:
• Neuromuscular blocking agents (depolarizing and non-depolarizing): Potentiation and prolongation of neuromuscular blockade is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection
• Narcotics and/or propofol: Potentiation and prolongation of analgesia and CNS depression is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection
• Dihydropyridine calcium channel blockers: An exaggerated hypotensive response is possible with the concomitant use of Magnesium Sulfate in 5% Dextrose Injection
• Drugs that may induce magnesium loss with concomitant use of Magnesium Sulfate in 5% Dextrose Injection: Alcohol, aminoglycosides, amphotericin B, cisplatin, cyclosporine, digitalis, loop diuretics, and thiazide diuretics

Please see accompanying full Prescribing Information for Magnesium Sulfate in 5% Dextrose Injection, USP.

Magnesium Sulfate in Water for Injection

2 grams/50 mL, 4 grams/100 mL, 4 grams/50 mL

Indications and Important Risk Information

Indications

Magnesium Sulfate in Water for Injection is indicated for the prevention and control of seizures in preeclampsia and eclampsia, respectively.  When used judiciously it effectively prevents and controls the convulsions of eclampsia without producing deleterious depression of the central nervous system of the mother or infant.  However, other effective drugs are available for this purpose.

Important Risk Information

Contraindications

Intravenous magnesium should not be given to mothers with toxemia of pregnancy during the two hours preceding delivery.

Warnings and Precautions

• FETAL HARM:  Continuous administration of magnesium sulfate beyond 5-7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus.  These bone abnormalities include skeletal demineralization and osteopenia.  In addition, cases of neonatal fracture have been reported.  The shortest duration of treatment that can lead to fetal harm is not known.  Magnesium sulfate should be used during pregnancy only if clearly needed.
  Parenteral use in the presence of renal insufficiency may lead to magnesium intoxication.
• Risk of Magnesium Toxicity:  Because magnesium is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment.  Urine output should be maintained at a level of 100 mL every four hours.
  Monitoring serum magnesium levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia.  Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium intoxication in eclampsia.
  Magnesium Sulfate in Water for Injection should be administered slowly to avoid producing hypermagnesemia.
• Adverse Reactions:  The adverse effects of parenterally administered magnesium usually are the result of magnesium intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis.  Hypocalcemia with signs of tetany secondary to magnesium sulfate therapy for eclampsia has been reported.
• Drug Interactions:
• Drug induced renal losses of magnesium occur with the following drugs or drug classes:
  Alcohol, aminoglycosides, amphotericin B, cisplatin, cyclosporine, digitalis, and diuretics

Please see accompanying full Prescribing Information for Magnesium Sulfate in Water for Injection.

MYXREDLIN (Insulin Human) in 0.9% Sodium Chloride Injection

100 units per 100 mL (1 unit/mL)

INDICATIONS AND IMPORTANT RISK INFORMATION

Indication

MYXREDLIN is a short-acting human insulin indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.

Important Risk Information

Contraindications

• During episodes of hypoglycemia

• Hypersensitivity to insulin human or any of the excipients in MYXREDLIN

Warnings and Precautions

• Hyper- or Hypoglycemia with Changes in Insulin Regimen: Carry out under close medical supervision and increase frequency of blood glucose monitoring.

• Administer MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels. Hypokalemia may be life-threatening if not treated.

• Individualize dose based on metabolic needs, blood glucose monitoring results, and glycemic control goal. Dosage adjustments may be needed with changes in nutrition, renal, or hepatic function or during acute illness.

• Adverse reactions observed with insulin human injection include hypoglycemia, allergic reactions, weight gain and edema.

• Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; such as shortness of breath, swelling of your ankles or feet, or sudden weight gain.

Dosage and Administration

• Inspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.

• Do not add supplementary medication or additives.

• Do not use in series connections.

• Do not shake or freeze. Discard unused portion.

Please see accompanying full Prescribing Information for MYXREDLIN (Insulin Human) in 0.9% Sodium Chloride Injection.

NEXTERONE (amiodarone HCl) Premixed Injection

150 mg/100 mL and 360 mg/200 mL

Indication and Important Risk Information

Indication

NEXTERONE is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy.

Important Risk Information

Contraindications

NEXTERONE is contraindicated in patients with:

• Known hypersensitivity to any of the components of NEXTERONE, including iodine

• Cardiogenic shock

• Marked sinus bradycardia

• Second- or third-degree atrioventricular (AV) block unless a functioning pacemaker is available

Warnings and Precautions

• Persistence of Adverse Effects: Because of the long half-life of amiodarone (9 to 36 days) and its metabolite desethylamiodarone (9 to 30 days), adverse reactions or interactions, as well as observed adverse effects, can persist following amiodarone withdrawal.
• Hypotension: Most often seen in the first several hours of treatment and likely related to the rate of infusion. In some cases, hypotension may be refractory and result in a fatal outcome. To treat: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion.
• Bradycardia and Atrioventricular Block: May require slowing the infusion rate or discontinuing NEXTERONE. In some patients, inserting a pacemaker is required. Have a temporary pacemaker available when treating a patient predisposed to bradycardia or AV block.
• Hepatic Injury: Acute hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated. Intravenous infusions at much higher concentrations and rates of infusion than those recommended appear to increase this risk. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. Consider reducing the rate of administration or withdrawing NEXTERONE if hepatic injury occurs.
• Proarrhythmia: NEXTERONE may cause a worsening of existing arrhythmias or precipitate a new arrhythmia, sometimes leading to fatal outcomes. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation by intravenous amiodarone. Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. Correct hypokalemia, hypomagnesemia, or hypocalcemia whenever possible before initiating treatment with NEXTERONE.
• Pulmonary Injury: There have been post-marketing reports of acute-onset (days to weeks) pulmonary injury. Some cases have progressed to respiratory failure or death. Monitor for new respiratory symptoms and evaluate appropriately. Obtain a baseline chest X-ray and pulmonary function tests in patients who are expected to be receiving amiodarone chronically.
• Loss of Vision: Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. Perform an ophthalmic examination if symptoms of visual impairment appear. Reevaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected.
• Thyroid Abnormalities: NEXTERONE inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T3 levels and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Monitor thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Hyperthyroidism may induce arrhythmia breakthrough. If any new signs of arrhythmia appear, the possibility of hyperthyroidism should be considered.
• Neonatal Injury: Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for adverse experiences, including cardiac, thyroid, neurodevelopmental, neurological, and growth effects in neonates. Inform the patient of the potential hazard to the fetus if NEXTERONE is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE.
• Hypersensitivity Reactions: Anaphylactic/anaphylactoid reactions have been reported, including shock (sometimes fatal), cardiac arrest, and the following manifestations: hypotension, tachycardia, hypoxia, cyanosis, rash, Stevens-Johnson syndrome, flushing, hyperhidrosis, and cold sweat.
• Adverse Reactions: The most common adverse reactions (1-2%) leading to discontinuation of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock. Other important adverse reactions are torsade de pointes, congestive heart failure, and liver function test abnormalities.
• Drug Interactions: Amiodarone is a substrate for CYP3A and CYP2C8, so inhibitors and inducers affect amiodarone exposure. Amiodarone inhibits p-glycoprotein and CYP1A2, CYP2C9, CYP2D6, and CYP3A, increasing exposure to other drugs.

Please see accompanying full Prescribing Information for NEXTERONE (amiodarone HCl) Premixed Injection.

Norepinephrine Bitartrate in 5% Dextrose Injection

4 mg equivalent of norepinephrine (16 mcg/mL) in 5% dextrose 250 mL
8 mg equivalent of norepinephrine (32 mcg/mL) in 5% dextrose 250 mL
16 mg equivalent of norepinephrine (64 mcg/mL) in 5% dextrose 250 mL

Indication and Important Risk Information

Indication

• Norepinephrine Bitartrate in Dextrose Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension.

Important Risk Information

• Contraindications: None.
• Tissue Ischemia: Administration of Norepinephrine Bitartrate in Dextrose Injection to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating Norepinephrine Bitartrate in Dextrose Injection. Avoid use in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction.
  Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients.
  Extravasation of Norepinephrine Bitartrate in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation.
  Avoid administration into the veins in the leg in elderly patients.
  Emergency Treatment of Extravasation: 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.
• Hypotension after Abrupt Discontinuation: Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the infusion rate while expanding blood volume with intravenous fluids.
• Cardiac Arrhythmias: Norepinephrine Bitartrate in Dextrose Injection elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias.
• Elderly Patients: May be at a greater risk of developing adverse reactions.
• Adverse Reactions: Most common adverse reactions are hypertension and bradycardia.
• Drug Interactions:
• Co-administration of Norepinephrine Bitartrate in Dextrose Injection with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) or with tricyclic antidepressants can cause severe, prolonged hypertension.
• Anti-diabetics: Norepinephrine Bitartrate in Dextrose Injection can decrease insulin sensitivity and raise blood glucose.
• Concomitant use of Norepinephrine Bitartrate in Dextrose Injection with halogenated anesthetics may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics.

Please see accompanying full Prescribing Information for Norepinephrine Bitartrate in 5% Dextrose Injection.

Vasopressin in 0.9% 100 mL Sodium Chloride Injection

20 units vasopressin (0.2 units/mL) in 0.9% sodium chloride
40 units vasopressin (0.4 units/mL) in 0.9% sodium chloride

Indications and Important Risk Information 

Indications 

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

Important Risk Information

• Contraindications: Vasopressin in Sodium Chloride Injection is contraindicated in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin.
• Worsening Cardiac Function: A decrease in cardiac index may be observed with the use of vasopressin.
• 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.
• Adverse Reactions:   
  – The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia, and ischemia (coronary, mesenteric, skin, digital).
• Drug Interactions: 
  – Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. 
  – Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. 
  – Co-administration of ganglionic blockers or drugs causing SIADH (syndrome of inappropriate antidiuretic hormone secretion) may increase the pressor response. 
  – Co-administration of drugs causing diabetes insipidus may decrease the pressor response. 
• Pregnancy: May induce tonic uterine contractions that could threaten the continuation of pregnancy. 

Please see accompanying full Prescribing Information for Vasopressin in 0.9% Sodium Chloride Injection.