Doxapram Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- DOPRAM
- DOXAPRAM HYDROCHLORIDE
Indications and Usage
Postanesthesia When the possibility of airway obstruction and/or hypoxia have been eliminated, doxapram may be used to stimulate respiration in patients with drug-induced postanesthesia respiratory depression or apnea other than that due to muscle relaxant drugs. 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 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 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 (see DOSAGE & ADMINISTRATION) 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.
Dosage and Administration
NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS) In Postanesthetic Use Table I. Dosage for postanesthetic use-I.V. and infusion. * Dose not to exceed 3 grams/24 hours. BY I.V. INJECTION (See Table I. Dosage for postanesthetic use—I.V.) 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 maximum total dosage by I.V. injection is 2 mg/kg. BY INFUSION The solution is prepared by adding 250 mg of doxapram (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 (See Table II. Dosage for drug-induced CNS depression.) Table II. Dosage for drug-induced CNS depression. * Mild Depression Class 0: Asleep, but can be aroused and can answer questions. Class 1: Comatose, will withdraw from painful stimuli, reflexes intact. † Moderate Depression Class 2: Comatose, will not withdraw from painful stimuli, reflexes intact. Class 3: Comatose, reflexes absent, no depression of circulation or respiration. METHOD ONE Using Single and/or Repeat Single I.V. Injections 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. Repeat same dose q 1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since DOPRAM does not affect the metabolism of CNS-depressant drugs. If relapse occurs, resume injections q 1 to
Contraindications
Doxapram is contraindicated in patients with known hypersensitivity to the drug or any of the injection components. Doxapram should not be used in patients with epilepsy or other convulsive disorders. Doxapram is contraindicated in patients with proven or suspected pulmonary embolism. Doxapram is contraindicated in patients with mechanical disorders of ventilation such as mechanical obstruction, muscle paresis (including neuromuscular blockade), flail chest, pneumothorax, acute bronchial asthma, pulmonary fibrosis, or other conditions resulting in restriction of the chest wall, muscles of respiration, or alveolar expansion. Doxapram is contraindicated in patients with evidence of head injury, cerebral vascular accident, or cerebral edema, and in those with significant cardiovascular impairment, uncompensated heart failure, severe coronary artery disease, or severe hypertension, including that associated with hyperthyroidism or pheochromocytoma. (See WARNINGS.)
Adverse Reactions
Adverse reactions reported coincident with the administration of DOPRAM (doxapram 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.
Overdosage
Signs and Symptoms Symptoms of overdosage are extensions of the pharmacologic effects of the drug. Excessive pressor effect, such as hypertension, tachycardia, skeletal muscle hyperactivity, and enhanced deep tendon reflexes may be early signs of overdosage. Therefore, the blood pressure, pulse rate, and deep tendon reflexes should be evaluated periodically and the dosage or infusion rate adjusted accordingly. Other effects may include agitation, confusion, sweating, cough, and dyspnea. Convulsive seizures are unlikely at recommended dosages. In unanesthetized animals, the convulsant dose is 70 times greater than the respiratory stimulant dose. Intravenous LD50 values in the mouse and rat were approximately 75 mg/kg and in the cat and dog were 40 to 80 mg/kg. Except for management of chronic obstructive pulmonary disease associated with acute hypercapnia, the maximum recommended dosage is 3 GRAMS/24 HOURS. (See DOSAGE & ADMINISTRATION.) Management There is no specific antidote for doxapram. Management should be symptomatic. Anticonvulsants, along with oxygen and resuscitative equipment should be readily available to manage overdosage manifested by excessive central nervous system stimulation. Slow administration of the drug and careful observation of the patient during administration and for some time subsequently are advisable. These precautions are to assure that the protective reflexes have been restored and to prevent possible post-hyperventilation or hypoventilation. There is no evidence that doxapram is dialyzable; further, the half-life of doxapram makes it unlikely that dialysis would be appropriate in managing overdose with this drug. Close