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Pronunciation
(DOKS a pram)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Respiratory and CNS stimulant for respiratory depression secondary to anesthesia, drug-induced CNS depression; acute hypercapnia secondary to COPD
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to doxapram or any component of the formulation; cardiovascular disease, cerebral edema, cerebral vascular accident, epilepsy, head injury, hyperthyroidism, mechanical disorders of ventilation, mechanical ventilation or neuromuscular blockade, pheochromocytoma, pulmonary embolism, or severe hypertension
Warnings/Precautions
Concerns related to adverse effects:
• CNS toxicity: May cause severe CNS toxicity, including seizures.
Disease-related concerns:
• Cerebrovascular disease: Use with caution in patients with cerebral disease; lowered pCO2 induced by hyperventilation produces cerebral vasoconstriction and decreased circulation.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in treating pulmonary disease; a pressor effect on pulmonary circulation may result in a fall in arterial pO2.
Concurrent drug therapy issues:
• Volatile anesthetics: If patient has received anesthesia with a volatile agent known to sensitize the myocardium to catecholamines, avoid use of doxapram until anesthetic has been eliminated.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <12 years of age.
Dosage form specific issues:
• Benzyl alcohol: Solution contains benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Other warnings/precautions:
• Administration: Hemolysis may result from rapid infusion.
• Appropriate use: Adequate airway required; consider airway protection in case of vomiting. Resuscitative equipment (in addition to anticonvulsants and oxygen) should be readily available. Doxapram is neither a nonspecific CNS depressant antagonist nor an opiate antagonist.
Adverse Reactions
Frequency not defined.
Cardiovascular: Arrhythmia, blood pressure increased, chest pain, chest tightness, flushing, heart rate changes, T waves lowered, ventricular tachycardia, ventricular fibrillation
Central nervous system: Apprehension, Babinski turns positive, disorientation, dizziness, hallucinations, headache, hyperactivity, pyrexia, seizure
Dermatologic: Burning sensation, pruritus
Gastrointestinal: Defecation urge, diarrhea, nausea, vomiting
Genitourinary: Spontaneous voiding, urinary retention
Hematologic: Hematocrit decreased, hemoglobin decreased, hemolysis, red blood cell count decreased
Local: Phlebitis
Neuromuscular & skeletal: Clonus, deep tendon reflexes increase, fasciculations, involuntary muscle movement, muscle spasm, paresthesia
Ocular: Pupillary dilatation
Renal: Albuminuria, BUN increased
Respiratory: Bronchospasm, cough, dyspnea, hiccups, hyperventilation, laryngospasm, rebound hypoventilation, tachypnea
Miscellaneous: Diaphoresis
Metabolism/Transport Effects
None known.
Drug Interactions
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Doxapram. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Storage
Store at 20°C to 25°C (68°F to 77°F).
Reconstitution
Drug-induced CNS depression or postanesthesia: Mix doxapram 250 mg in 250 mL of D5W, D10W, or NS.
COPD-associated hypercapnia: Mix doxapram 400 mg in 180 mL of D5W, D10W, or NS (final concentration: 2 mg/mL).
Compatibility
Stable in D5W, D10W, NS.
Y-site administration: Compatible: Caffeine citrate, erythromycin lactobionate, gentamicin, metoclopramide, ranitidine, vancomycin. Incompatible: Clindamycin. Variable (consult detailed reference): Ampicillin, calcium chloride, calcium gluconate, cefazolin, ceftazidime, fentanyl, heparin, insulin (regular), metronidazole, oxacillin, phenobarbital.
Compatibility in syringe: Compatible: Amikacin, bumetanide, chlorpromazine, cimetidine, cisplatin, cyclophosphamide, dopamine, doxycycline, epinephrine, hydroxyzine, isoniazid, lincomycin, methotrexate, phytonadione, pyridoxine, terbutaline, thiamine, tobramycin, vincristine. Incompatible: Aminophylline, ascorbic acid injection, cefotaxime, cefotetan, cefuroxime, dexamethasone sodium phosphate, diazepam, digoxin, dobutamine, folic acid, furosemide, hydrocortisone sodium succinate, ketamine, methylprednisolone sodium succinate, thiopental.
Mechanism of Action
Stimulates respiration through action on respiratory center in medulla or indirectly on peripheral carotid chemoreceptors
Pharmacodynamics/Kinetics
Onset of action: Respiratory stimulation: I.V.: 20-40 seconds
Peak effect: 1-2 minutes
Duration: 5-12 minutes
Half-life elimination, serum: Adults: Mean: 3.4 hours
Dosage
Respiratory depression following anesthesia:
Intermittent injection: Initial: 0.5-1 mg/kg; may repeat at 5-minute intervals (only in patients who demonstrate initial response); maximum total dose: 2 mg/kg
I.V. infusion: Initial: 5 mg/minute until adequate response or adverse effects seen; decrease to 1-3 mg/minute; maximum total dose: 4 mg/kg
Drug-induced CNS depression:
Intermittent injection: Initial: Priming dose of 1-2 mg/kg, repeat after 5 minutes; may repeat at 1-2 hour intervals (until sustained consciousness); maximum: 3 g/day. May repeat in 24 hours if necessary.
I.V. infusion: Initial: Priming dose of 1-2 mg/kg, repeat after 5 minutes. If no response, wait 1-2 hours and repeat. If some stimulation is noted, initiate infusion at 1-3 mg/minute (depending on size of patient/depth of CNS depression); suspend infusion if patient begins to awaken. Infusion should not be continued for >2 hours. May reinstitute infusion as described above, including bolus, after rest interval of 30 minutes to 2 hours; maximum: 3 g/day
Acute hypercapnia secondary to COPD: I.V. infusion: Initial: Initiate infusion at 1-2 mg/minute (depending on size of patient/depth of CNS depression); may increase to maximum rate of 3 mg/minute; infusion should not be continued for >2 hours. Monitor arterial blood gases prior to initiation of infusion and at 30-minute intervals during the infusion (to identify possible development of acidosis/CO2 retention). Additional infusions are not recommended (per manufacturer).
Administration: I.V.
Avoid rapid infusion.
Monitoring Parameters
Monitor heart rate, blood pressure, reflexes, CNS status, ECG, arterial blood gases (COPD)
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Doxapram should not be used as a drug of choice to treat anesthesia-induced respiratory depression due to its transient effect.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause CNS stimulation, restlessness, irritability, or hallucinations
Mental Health: Effects on Psychiatric Treatment
May cause hypertensive crisis if used with MAO inhibitors
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 20 mg/mL (20 mL)
Dopram®: 20 mg/mL (20 mL) [contains benzyl alcohol]
References
Barrington KJ, Finer NN, Torok-Both G, et al, “Dose-Response Relationship of Doxapram in the Therapy for Refractory Idiopathic Apnea of Prematurity,” Pediatrics, 1987, 80(1):22-7.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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