Doxapram Hydrochloride Injection

Postanesthesia

1. When the possibility of airway obstruction and/or hypoxia have been eliminated, Doxapram Hydrochloride Injection may be used to stimulate respiration in patients with drug-induced postanesthesia respiratory depression or apnea other than that due to muscle relaxant drugs.
2. To pharmacologically stimulate deep breathing in the postoperative patient. (A quantitative method of assessing oxygenation, such as pulse oximetry, is recommended.)

Drug-Induced Central Nervous System Depression

Exercising care to prevent vomiting and aspiration, Doxapram Hydrochloride Injection may be used to stimulate respiration, hasten arousal, and to encourage the return of laryngopharyngeal reflexes in patients with mild to moderate respiratory and CNS depression due to drug overdosage.

Chronic Pulmonary Disease Associated with Acute Hypercapnia

Doxapram Hydrochloride Injection is indicated as a temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease. Its use should be for a short period of time as an aid in the prevention of elevation of arterial CO2 tension during the administration of oxygen.

It should not be used in conjunction with mechanical ventilation.

Stimulating or improving breathing in patients after surgery or overdose of certain medicines. It is also used to treat chronic lung disease associated with excessive carbon dioxide in the blood.

Doxapram Hydrochloride Injection is an analeptic. It works by stimulating the breathing center of the brain by altering the natural chemicals (neurotransmitters) in the brain.

NOTE: CONTAINS BENZYL ALCOHOL

In Postanesthetic Use

Table I. Dosage for postanesthetic use—I.V. and infusion.

By I.V. Injection

The recommended dose for I.V. administration is 0.5 – 1 mg/kg for a single injection and at 5-minute intervals. Careful observation of the patient during administration and for some time subsequently are advisable. The ma ximum total dosage by I.V. injection is 2 mg/kg.

By Infusion

The solution is prepared by adding 250 mg of Doxapram Hydrochloride Injection (12.5 mL) to 250 mL of dextrose 5% or 10% in water or normal saline solution. The infusion is initiated at a rate of approximately 5 mg/minute until a satisfactory respiratory response is observed, and maintained at a rate of 1 to 3 mg/minute. The rate of infusion should be adjusted to sustain the desired level of respiratory stimulation with a minimum of side effects. The maximum total dosage by infusion is 4 mg/kg, or approximately 300 mg for the average adult.

In the Management of Drug-Induced CNS Depression

Table II. Dosage for drug-induced CNS depression.

Method One

Using Single and/or Repeat Single I.V. Injections

1. Give priming dose of 2 mg/kg body weight and repeat in 5 minutes. The priming dose for moderate depression is 2 mg/kg and the priming dose for mild depression is 1 mg/kg.
2. Repeat same dose q 1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection) does not affect the metabolism of CNS-depressant drugs.
3. If relapse occurs, resume injections q 1 to 2h until arousal is sustained, or total maximum daily dose (3 grams) is given. After maximum dose has been given (3 grams), allow patient to sleep until 24 hours have elapsed from first injection of Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection), using assisted or automatic respiration if necessary.
4. Repeat procedure the following day until patient breathes spontaneously and sustains desired level of consciousness, or until maximum dosage (3 grams) is given.
5. Repetitive doses should be administered only to patients who have shown response to the initial dose.
6. Failure to respond appropriately indicates the need for neurologic evaluation for a possible central nervous system source of sustained coma.

Method Two

By Intermittent I.V. Infusion

1. Give priming dose as in Method One.
2. If patient wakens, watch for relapse; if no response, continue general supportive treatment for 1 to 2 hours and repeat priming dose of Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection). If some respiratory stimulation occurs, prepare I.V. infusion by adding 250 mg of Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection) (12.5 mL) to 250 mL of saline or dextrose solution. Deliver at rate of 1 to 3 mg/min (60 to 180 mL/hr) according to size of patient and depth of coma. Discontinue Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection) if patient begins to waken or at end of 2 hours.
3. Continue supportive treatment for ½ to 2 hours and repeat Step b.
4. Do not exceed 3 grams/day.

Chronic Obstructive Pulmonary Disease Associated with Acute Hypercapnia

1. One vial of Doxapram Hydrochloride Injection (400 mg) should be mixed with 180 mL of dextrose 5% or 10% or normal saline solution (concentration of 2 mg/mL). The infusion should be started at 1 to 2 mg/minute (½ to 1 mL/minute); if indicated, increase to a maximum of 3 mg/minute. Arterial blood gases should be determined prior to the onset of Doxapram Hydrochloride Injection's administration and at least every half hour during the two hours of infusion to insure against the insidious development of CO-RETENTION AND ACIDOSIS. Alteration of oxygen concentration or flow rate may necessitate adjustment in the rate of Doxapram Hydrochloride Injection infusion.
2. Predictable blood gas patterns are more readily established with a continuous infusion of Doxapram Hydrochloride Injection. If the blood gases show evidence of deterioration, the infusion of Doxapram Hydrochloride Injection should be discontinued.
3. ADDITIONAL INFUSIONS BEYOND THE SINGLE MAXIMUM TWO HOUR ADMINISTRATION PERIOD ARE NOT RECOMMENDED.

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

Diluent Compatibility

Doxapram Hydrochloride Injection hydrochloride is compatible with 5% and 10% dextrose in water or normal saline.

Incompatibility

ADMIXTURE OF Doxapram Hydrochloride Injection WITH ALKALINE SOLUTIONS SUCH AS 2.5% THIOPENTAL SODIUM, SODIUM BICARBONATE, FUROSEMIDE, OR AMINOPHYLLINE WILL RESULT IN PRECIPITATION OR GAS FORMATION.

Doxapram Hydrochloride Injection is also not compatible with ascorbic acid, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefuroxime sodium, folic acid, dexamethasone disodium phosphate, diazepam, hydrocortisone sodium phospate, methylprednisolone sodium, or hydrocortisone sodium succinate.

Admixture of Doxapram Hydrochloride Injection and ticarcillin disodium results in an 18% loss of Doxapram Hydrochloride Injection in 3 hours. When Doxapram Hydrochloride Injection is mixed with minocycline hydrochloride, there is a loss of 8% of Doxapram Hydrochloride Injection in 3 hours and a 13% loss of Doxapram Hydrochloride Injection in 6 hours.

How supplied

Doxapram Hydrochloride Injection Injection (Doxapram Hydrochloride Injection hydrochloride injection, USP) containing 20 mg of Doxapram Hydrochloride Injection hydrochloride per mL with benzyl alcohol 0.9% as the preservative is available in:

20 mL multiple dose vials in packages of 6 (NDC 60977-144-02).

CONTAINS BENZYL ALCOHOL.

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F).

Manufactured by: Baxter Healthcare Corporation Deerfield, IL 60015 USA. For Product Inquiry 1 800 ANA DRUG (1-800-262-3784).

See also:
What is the most important information I should know about Doxapram Hydrochloride Injection?

Due to its benzyl alcohol content, Doxapram Hydrochloride Injection injection is contraindicated in neonates.

Doxapram Hydrochloride Injection HCL should not be used in patients with epilepsy or other convulsive disorders.

Doxapram Hydrochloride Injection HCL is contraindicated in patients with mechanical disorders of ventilation such as mechanical obstruction, muscle paresis, flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis or other conditions resulting in restriction of chest wall, muscles of respiration or alveolar expansion.

Doxapram Hydrochloride Injection HCL is contraindicated in patients with evidence of head injury or cerebral vascular accident and in those with significant cardiovascular impairment, severe hypertension, or known hypersensitivity to the drug or any of the injection components.

Use Doxapram Hydrochloride Injection as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Doxapram Hydrochloride Injection is usually administered as an injection at your doctor's office, hospital, or clinic.
• If Doxapram Hydrochloride Injection contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.
• If you miss a dose of Doxapram Hydrochloride Injection, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Doxapram Hydrochloride Injection.

Use: Labeled Indications

Respiratory stimulant for respiratory depression secondary to anesthesia, mild-to-moderate drug-induced respiratory and CNS depression; acute hypercapnia secondary to COPD

Note: In general, the use of Doxapram Hydrochloride Injection as a respiratory stimulant in adults is limited; alternate therapies are preferred.

Administration of Doxapram Hydrochloride Injection to patients who are receiving sympathomimetic or monoamine oxidase inhibiting drugs may result in an additive pressor effect.

In patients who have received neuromuscular blocking agents, Doxapram Hydrochloride Injection may temporarily mask the residual effects of these drugs.

In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of Doxapram Hydrochloride Injection should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation.

There may be an interaction between Doxapram Hydrochloride Injection and aminophylline and between theophylline manifested by increased skeletal muscle activity, agitation, and hyperactivity.

See also:
What are the possible side effects of Doxapram Hydrochloride Injection?

Adverse reactions reported coincident with the administration of Doxapram Hydrochloride Injection (Doxapram Hydrochloride Injection hydrochloride, USP) include:

1. Central and Autonomic Nervous Systems

Pyrexia, flushing, sweating; pruritus and paresthesia, such as a feeling of warmth, burning, or hot sensation, especially in the area of genitalia and perineum; apprehension, disorientation, pupillary dilatation, hallucinations, headache, dizziness, hyperactivity, involuntary movements, muscle spasticity, muscle fasciculations, increased deep tendon reflexes, clonus, bilateral Babinski, and convulsions.

2. Respiratory

Dyspnea, cough, hyperventilation, tachypnea, laryngospasm, bronchospasm, hiccough, and rebound hypoventilation.

3. Cardiovascular

Phlebitis, variations in heart rate, lowered T-waves, arrhythmias (including ventricular tachycardia and ventricular fibrillation), chest pain, tightness in chest. A mild to moderate increase in blood pressure is commonly noted and may be of concern in patients with severe cardiovascular diseases.

4. Gastrointestinal

Nausea, vomiting, diarrhea, desire to defecate.

5. Genitourinary

Stimulation of urinary bladder with spontaneous voiding; urinary retention. Elevation of BUN and albuminuria.

6. Hemic and Lymphatic

Hemolysis with rapid infusion. A decrease in hemoglobin, hematocrit, or red blood cell count has been observed in postoperative patients. In the presence of pre-existing leukopenia, a further decrease in WBC has been observed following anesthesia and treatment with Doxapram Hydrochloride Injection hydrochloride.

A central respiratory stimulant with a brief duration of action. (From Martindale, The Extra Pharmocopoeia, 30th ed, p1225)