Pridam

Zur Blutdruckkontrolle in bestimmten akuten blutdrucksenkenden Zuständen (z., Phäochromocytomektomie, Sympathektomie, Poliomyelitis, Wirbelsäulenanästhesie, Myokardinfarkt, Septikämie, Bluttransfusion und Arzneimittelreaktionen).

Als Ergänzung bei der Behandlung von Herzstillstand und tiefgreifender Hypotonie.

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

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, Pridam can be administered before and concurrently with blood volume replacement.

Diluent

Pridam 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 Pridam to 1,000 mL of a 5 percent dextrose containing solution. Each mL of this dilution contains 4 mcg of the base of Pridam. 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 Pridam 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 Pridam 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 Pridam 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. [Pridam'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, Pridam 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.

WARNINGS

Pridam 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.

Pridam Bitartrate 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. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

PRECAUTIONS

General

Avoid Hypertension

Because of the potency of Pridam and because of varying response to pressor substances, the possibility always exists that dangerously high blood pressure may be produced with overdoses of this pressor agent. It is desirable, therefore, to record the blood pressure every two minutes from the time administration is started until the desired blood pressure is obtained, then every five minutes if administration is to be continued.

The rate of flow must be watched constantly, and the patient should never be left unattended while receiving Pridam. Headache may be a symptom of hypertension due to overdosage.

Site of Infusion

Whenever possible, infusions of Pridam should be given into a large vein, particularly an antecubital vein because, when administered into this vein, the risk of necrosis of the overlying skin from prolonged vasoconstriction is apparently very slight. Some authors have indicated that the femoral vein is also an acceptable route of administration. A catheter tie-in technique should be avoided, if possible, since the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug. Occlusive vascular diseases (for example, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger's disease) are more likely to occur in the lower than in the upper extremity. Therefore, one should avoid the veins of the leg in elderly patients or in those suffering from such disorders. Gangrene has been reported in a lower extremity when infusions of Pridam were given in an ankle vein.

Extravasation

The infusion site should be checked frequently for free flow. Care should be taken to avoid extravasation of Pridam into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Blanching along the course of the infused vein, sometimes without obvious extravasation, has been attributed to vasa vasorum constriction with increased permeability of the vein wall, permitting some leakage.

This also may progress on rare occasions to superficial slough, particularly during infusion into leg veins in elderly patients or in those suffering from obliterative vascular disease. Hence, if blanching occurs, consideration should be given to the advisability of changing the infusion site at intervals to allow the effects of local vasoconstriction to subside.

IMPORTANT - Antidote for Extravasation Ischemia: To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of Regitine® (brand of phentolamine), an adrenergic blocking agent. A syringe with a fine hypodermic needle should be used, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance. Sympathetic blockade 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.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Studies have not been performed.

Pregnancy Category C

Animal reproduction studies have not been conducted with Pridam. It is also not known whether Pridam can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pridam should be given to a pregnant woman only if clearly needed.

Nursing Mothers

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 Pridam is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients has not been established.

Geriatric Use

Clinical studies of Pridam 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.

Pridam infusions should not be administered into the veins in the leg in elderly patients (see PRECAUTIONS, General).

Folgende Reaktionen können auftreten:

Körper als Ganzes: Ischämische Verletzung durch starke Vasokonstriktorwirkung und Gewebehypoxie.

Herz-Kreislauf-System: Bradykardie, wahrscheinlich als Reflexergebnis eines Blutdruckanstiegs, Arrhythmien.

Nervensystem: Angst, vorübergehende Kopfschmerzen.

Atmungssystem: Atembeschwerden.

Haut und Gliedmaßen: Extravasationsnekrose an der Injektionsstelle.

Eine längere Verabreichung eines wirksamen Vasopressors kann zu einer Abnahme des Plasmabolumens führen, die durch eine geeignete Flüssigkeits- und Elektrolytersatztherapie kontinuierlich korrigiert werden sollte. Wenn das Plasmavolumen nicht korrigiert wird, kann die Hypotonie erneut auftreten, wenn Pridam abgesetzt wird, oder der Blutdruck kann auf das Risiko einer schweren peripheren und viszeralen Vasokonstriktion aufrechterhalten werden (z.verminderte Nierenperfusion) mit verminderter Blutfluss- und Gewebeperfusion mit anschließender Gewebehypoxie und Laktatazidose und möglicher ischämischer Verletzung. Gangrän der Extremitäten wurde selten berichtet.

Überdosierungen oder herkömmliche Dosen bei überempfindlichen Personen (z.Hyperthyreose-Patienten) verursachen schwere Hypertonie mit heftigen Kopfschmerzen, Photophobie, stechenden retrosternalen Schmerzen, Blässe, intensivem Schwitzen und Erbrechen.

Overdosage with Pridam may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of accidental overdosage, as evidenced by excessive blood pressure elevation, discontinue Pridam until the condition of the patient stabilizes.