Norepinephrine Bitartrat-Water

Drug overview for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Generic name: NOREPINEPHRINE BITARTRATE IN STERILE WATER
Drug class: Pressors
Therapeutic class: Cardiovascular Therapy Agents

Norepinephrine bitartrate is an endogenous catecholamine vasopressor that predominantly acts by a direct effect on alpha-adrenergic receptors and to a lesser extent on beta-adrenergic receptors.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following dosing information is available for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Dosing
Administration
Dosing Information
Generic

Avoid abrupt withdrawal of norepinephrine infusion; discontinue by reducing the flow rate gradually.

Norepinephrine bitartrate is administered by IV infusion. To minimize the risk of necrosis, infusion of the drug should be given into a large vein; avoid infusions into the veins of the leg in elderly patients or in patients with occlusive vascular disease of the legs. Care must be taken to avoid extravasation because local necrosis may result; check the infusion site frequently for free flow and monitor for signs of extravasation.

Visually inspect solutions of norepinephrine for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use the drug if it is discolored (e.g., pink, dark yellow) or contains any particulate matter. Store norepinephrine bitartrate at 20-25degreesC (excursions permitted to 15-30degreesC) in the original carton until the time of administration and protect from light.

Discard any unused portion. Avoid contact of the drug with iron salts, alkalies, or oxidizing agents. Administer whole blood or plasma, if indicated during therapy with norepinephrine, separately.

Norepinephrine bitartrate injection concentrate must be diluted prior to administration; alternatively, commercially available solutions of norepinephrine in 5% dextrose or norepinephrine in 0.9% sodium chloride may be used without dilution.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Dihydroergotamine/Sympathomimetics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1) CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1) DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.	DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

Drug Interaction

Drug Names

Dihydroergotamine/Sympathomimetics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1)

CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1)

DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.

DIHYDROERGOTAMINE MESYLATE, MIGRANAL, TRUDHESA

There are 4 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Ergot Alkaloids/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels. CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary. DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.	ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT
Selected Inhalation Anesthetic Agents/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1) CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1) DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics.	DESFLURANE, FORANE, ISOFLURANE, SEVOFLURANE, SUPRANE, TERRELL, ULTANE
Selected Direct-Acting Sympathomimetics/Tricyclic Compounds SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake. CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider avoiding the concurrent use of direct-acting sympathomimetics and tricyclic compounds. If concurrent use of direct-acting sympathomimetics and tricyclic compounds is warranted, the initial dose of the sympathomimetic should be lowered and the patient should be monitored for adverse cardiovascular effects. Use of tricyclic compounds and other sympathomimetics should be approached with caution. DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Other direct and mixed acting sympathomimetic amines have also been reported to interact with tricyclic antidepressants. These include norepinephrine, phenylephrine, dopamine, and methoxamine. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics.	AMITRIPTYLINE HCL, AMOXAPINE, ANAFRANIL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, DESIPRAMINE HCL, DOXEPIN HCL, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, SILENOR, TRIMIPRAMINE MALEATE
Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)	ADREVIEW

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Sympathomimetics (Direct, Mixed-Acting)/Guanethidine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Direct or mixed-acting sympathomimetics may inhibit uptake of guanethidine at the adrenergic neuron. CLINICAL EFFECTS: Decreased antihypertensive effectiveness. Effects may be seen for several days after discontinuation of the direct or mixed-acting sympathomimetic. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If both drugs are administered, adjust the guanethidine dose as needed based on blood pressure. DISCUSSION: Documentation supports routine monitoring of this interaction. It should be noted that this interaction can occur quickly.	GUANETHIDINE HEMISULFATE
Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.	METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL
Entacapone; Opicapone/COMT-Metabolized Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Entacapone and opicapone are selective and reversible inhibitors of catechol-O-methyltransferase (COMT) and drugs that are metabolized by COMT can not be fully metabolized when given with entacapone or opicapone.(1) CLINICAL EFFECTS: COMT-metabolized agents can interact with entacapone or opicapone and may result in an increased heart rates, arrhythmias, or an excessive change in blood pressure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturers of entacapone and opicapone recommend using caution when administering entacapone or opicapone and a COMT-metabolized agent regardless of the route of administration (including inhalation).(1-3) DISCUSSION: In an interaction study, ventricular tachycardia was observed after epinephrine and entacapone administration.(1) Another study on the effect of entacapone given with isoproterenol and epinephrine concluded that entacapone may potentiate the chronotropic and arrhythmogenic effects of isoproterenol and epinephrine.(4)	CARBIDOPA-LEVODOPA-ENTACAPONE, ENTACAPONE, ONGENTYS

The following contraindication information is available for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*None.

There are 0 contraindications.

There are 4 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Hypercapnia
Hypovolemia
Hypoxia
Thrombotic disorder

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hypertension
Occlusive vascular disease

The following adverse reaction information is available for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse reactions associated with norepinephrine are ischemic injury, bradycardia, anxiety, transient headache, respiratory difficulty, and extravasation necrosis at injection site.

There are 9 severe adverse reactions.

More Frequent	Less Frequent
None.	Bradycardia Hypertension Tachycardia Ventricular arrhythmias

Rare/Very Rare
Angina Extravasation injury Hypertensive crisis Pulmonary edema Tissue necrosis

There are 14 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Nausea Vomiting	Dizziness Dyspnea Nervousness Pallor Palpitations Peripheral vasoconstriction Symptoms of anxiety Tremor

Rare/Very Rare
Blurred vision Neck pain Pruritus of skin

The following precautions are available for NOREPINEPHRINE BITARTRAT-WATER (norepinephrine bitartrate in sterile water):

Pediatric
Pregnant
Lactation
Geriatric

Safety and effectiveness in pediatric patients have not been established.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Limited data on the use of norepinephrine in pregnant women at the time of delivery have not identified an increased risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus from acute hypotensive states that are medical emergencies in pregnancy (e.g., in septic shock, myocardial infarction, and stroke); these can be fatal if untreated. Delaying necessary treatment 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 norepinephrine on the fetus. In animal reproduction studies, high doses of IV norepinephrine resulted in lowered maternal placental blood flow; however, the clinical relevance to changes in the human fetus is unknown. Studies of norepinephrine administration to pregnant animals demonstrated decreases in fetal oxygenation, urine and lung liquid flow, production of cataracts, fetal microscopic liver abnormalities, and delayed skeletal ossification.

There are no data on the presence of norepinephrine in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Because of its short half-life and poor oral bioavailability, clinically relevant exposure of norepinephrine in the infant is unlikely.

Clinical studies of norepinephrine bitartrate did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Clinical experience to date has not identified any differences in responses between geriatric and younger patients. If norepinephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group. Do not infuse into the leg veins of geriatric patients.