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Levophed (norepinephrine bitartrate) for Hypotension: Dosage & Warnings

What is Levophed, and how does it work?

Levophed (norepinephrine bitartrate) injection is a prescription medication used for

What are the side effects of Levophed?

The following reactions can occur:

  • Body As A Whole: Ischemic injury due to potent
    vasoconstrictor action and tissue
    hypoxia.
  • Cardiovascular System:
    Bradycardia, probably as a
    reflex result of a rise in blood pressure, arrhythmias.
  • Nervous System: Anxiety, transient headache.
  • Respiratory System: Respiratory difficulty.
  • Skin and Appendages: Extravasation
    necrosis at
    injection site.

Prolonged administration of any potent vasopressor may
result in plasma volume depletion which should be continuously corrected by
appropriate fluid and electrolyte replacement therapy. If plasma volumes are
not corrected, hypotension may recur when
Levophed is discontinued, or blood
pressure may be maintained at the risk of severe peripheral and visceral
vasoconstriction (e.g., decreased renal perfusion) with diminution in blood
flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis
and possible ischemic injury. Gangrene of extremities has been rarely reported.

Overdoses or conventional doses in hypersensitive persons
(e.g., hyperthyroid patients) cause severe hypertension with violent headache,
photophobia, stabbing retrosternal pain, pallor, intense sweating, and
vomiting.

What is the dosage for Levophed?

Norepinephrine Bitartrate Injection is a concentrated,
potent drug which must be diluted in dextrose
containing solutions prior to infusion. An infusion of Levophed should be given
into a large vein.

Restoration Of Blood Pressure In Acute Hypotensive States

  • Blood volume depletion should always be corrected as
    fully as possible before any vasopressor is administered.
  • When, as an emergency
    measure, intraaortic pressures must be maintained to prevent cerebral or
    coronary artery
    ischemia,
    Levophed can be administered before and concurrently
    with blood volume replacement.
Diluent
  • Levophed should be diluted in 5 percent dextrose
    injection or 5 percent dextrose and sodium chloride injections.
  • These dextrose
    containing fluids are protection against significant loss of potency due to
    oxidation.
  • Administration in saline solution alone is not recommended.
  • Whole
    blood or plasma, if indicated to increase blood volume, should be administered
    separately (for example, by use of a Y-tube and individual containers if given
    simultaneously).
Average Dosage
  • Add a 4 mL ampul (4 mg) of Levophed to 1,000 mL of a 5
    percent dextrose containing solution. Each mL of this dilution contains 4 mcg
    of the base of Levophed.
  • Give this solution by intravenous infusion. Insert a
    plastic intravenous
    catheter through a suitable bore needle well advanced
    centrally into the vein and securely fixed with adhesive tape, avoiding, if
    possible, a catheter tie-in technique as this promotes
    stasis.
  • An IV
    drip
    chamber or other suitable metering device is
    essential to permit an accurate
    estimation of the rate of flow in drops per minute. After observing the response
    to an initial dose of 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute,
    adjust the rate of flow to establish and maintain a low normal blood pressure
    (usually 80 mm
    Hg to 100 mm Hg
    systolic) sufficient to maintain the
    circulation
    to vital organs.
  • In previously
    hypertensive patients, it is recommended that
    the blood pressure should be raised no higher than 40 mm Hg below the
    preexisting systolic pressure. The average maintenance dose ranges from 0.5 mL
    to 1 mL per minute (from 2 mcg to 4 mcg of base).
High Dosage
  • Great individual variation occurs in the dose required to
    attain and maintain an adequate blood pressure.
  •  In all cases, dosage of
    Levophed should be titrated according to the response of the patient.
  • Occasionally much larger or even enormous daily doses (as high as 68 mg base or
    17 ampuls) may be necessary if the patient remains hypotensive, but
    occult
    blood volume depletion should always be suspected and corrected when present.
  • Central venous pressure monitoring is usually helpful in detecting and treating
    this situation.
Fluid Intake
  • The degree of dilution depends on clinical fluid volume
    requirements.
  • If large volumes of fluid (dextrose) are needed at a flow rate
    that would involve an excessive dose of the
    pressor agent per unit of time, a
    solution more dilute than 4 mcg per mL should be used.
  • On the other hand, when
    large volumes of fluid are clinically undesirable, a concentration greater than
    4 mcg per mL may be necessary.
Duration Of Therapy
  • The infusion should be continued until adequate blood
    pressure and tissue
    perfusion are maintained without therapy.
  • Infusions of
    Levophed should be reduced gradually, avoiding abrupt withdrawal.
  • In some of
    the reported cases of
    vascular collapse due to
    acute myocardial infarction,
    treatment was required for up to six days.

Adjunctive Treatment In Cardiac Arrest

  • Infusions of Levophed are usually administered
    intravenously during cardiac
    resuscitation to restore and maintain an adequate
    blood pressure after an effective heartbeat and
    ventilation have been established
    by other means. [Levophed’s powerful beta-adrenergic stimulating action is also
    thought to increase the strength and effectiveness of systolic contractions
    once they occur.]
Average Dosage
  • To maintain systemic blood pressure during the management
    of cardiac arrest, Levophed is used in the same manner as described under
    Restoration of Blood Pressure in Acute  Hypotensive States.
  • Parenteral drug products should be inspected visually for
    particulate matter and discoloration prior to use, whenever solution and
    container permit.
  • Do not use the solution if its color is pinkish or darker
    than slightly yellow or if it contains a precipitate.
  • Avoid contact with iron salts, alkalis, or oxidizing
    agents.

What drugs interact with Levophed?

Cyclopropane and halothane anesthetics increase cardiac
autonomic irritability and therefore seem to sensitize the myocardium to the
action of intravenously administered epinephrine or norepinephrine. Hence, the
use of Levophed during cyclopropane and halothane anesthesia is generally
considered contraindicated because of the risk of producing ventricular
tachycardia or fibrillation. The same type of cardiac arrhythmias may result
from the use of Levophed in patients with profound hypoxia or hypercarbia.

Levophed should be used with extreme caution in patients
receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the
triptyline or imipramine types, because severe, prolonged hypertension may
result.

Is Levophed safe to use while pregnant or breastfeeding?

  • It is also not known whether Levophed can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
  • Levophed should be given to a pregnant woman only if clearly needed.
  • It is not known whether this drug is excreted in human milk.
  • Because many drugs are excreted in human milk, caution should be exercised when
    Levophed is administered to a nursing woman.

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