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Doxapram: Drug information

Doxapram: Drug information
(For additional information see "Doxapram: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Dopram
Pharmacologic Category
  • Respiratory Stimulant
Dosing: Adult

Note: Although manufacturer's dosing recommendations are presented for these FDA-approved indications, use of doxapram has largely been replaced by alternate preferred agents.

Respiratory depression following anesthesia

Respiratory depression following anesthesia: IV:

Intermittent injection: Initial: 0.5 to 1 mg/kg; may repeat at 5-minute intervals (only in patients who demonstrate initial response); maximum single injection dose: 1.5 mg/kg; maximum total dose: 2 mg/kg.

IV infusion: Initial: 5 mg/minute until adequate response or adverse effects seen; decrease to 1 to 3 mg/minute; maximum total dose: 4 mg/kg.

Drug-induced CNS depression

Drug-induced CNS depression: IV:

Intermittent injection: Initial: Priming dose of 1 to 2 mg/kg; repeat after 5 minutes (only in patients who demonstrate initial response); may repeat at 1 to 2 hour intervals (until sustained consciousness); maximum: 3000 mg/day. May repeat in 24 hours if necessary.

IV infusion: Initial: Priming dose of 1 to 2 mg/kg repeated in 5 minutes. If no response, wait 1 to 2 hours and repeat priming dose. If some stimulation is noted, initiate infusion at 1 to 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: 3000 mg/day.

Acute hypercapnia secondary to COPD

Acute hypercapnia secondary to COPD: IV infusion: Initial: Initiate infusion at 1 to 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. Additional infusions are not recommended (per manufacturer).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Doxapram: Pediatric drug information")

Note: Although manufacturer's dosing recommendations are presented for these FDA-approved indications, use of doxapram has largely been replaced by alternate preferred agents.

Drug-induced CNS depression

Drug-induced CNS depression:

Children ≥12 years and Adolescents: IV:

Intermittent injection: Initial: Priming dose of 1 to 2 mg/kg; repeat after 5 minutes; may repeat at 1 to 2 hour intervals until sustained consciousness; if relapse occurs may resume repeat doses at 1 to 2 hour intervals until sustained consciousness or maximum dose reached; maximum daily dose: 3,000 mg/day. May repeat in 24 hours if necessary; repeat doses should only be given to patient who demonstrated a response to initial dose.

IV infusion: Initial: Priming dose of 1 to 2 mg/kg; repeat after 5 minutes. If no response, wait 1 to 2 hours and repeat priming dose. If some respiratory stimulation is noted, initiate infusion at 1 to 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 daily dose: 3,000 mg/day.

Respiratory depression following anesthesia

Respiratory depression following anesthesia:

Children ≥12 years and Adolescents: IV:

Intermittent injection: Initial: 0.5 to 1 mg/kg; may repeat at 5-minute intervals; maximum single injection dose: 1.5 mg/kg; maximum total dose: 2 mg/kg.

Continuous IV infusion: Initial: 5 mg/minute until adequate response or adverse effects seen; decrease to 1 to 3 mg/minute; maximum total dose: 4 mg/kg (in an average adult, ~300 mg total dose).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Cardiovascular: Cardiac arrhythmia, change in pulse, chest pain, chest tightness, flattened T wave on ECG, flushing, increased blood pressure, phlebitis, ventricular fibrillation, ventricular tachycardia

Central nervous system: Apprehension, clonus, disorientation, dizziness, hallucination, headache, hyperactivity, hyperreflexia, involuntary muscle movements, paresthesia, positive Babinski sign, seizure

Dermatologic: Burning sensation of skin, diaphoresis, pruritus

Endocrine & metabolic: Albuminuria

Gastrointestinal: Bowel urgency, diarrhea, hiccups, nausea, vomiting

Genitourinary: Urinary incontinence, urinary retention

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, hemolysis, decreased red blood cells

Neuromuscular & skeletal: Fasciculations, laryngospasm, muscle spasm

Ophthalmic: Mydriasis

Renal: Increased blood urea nitrogen

Respiratory: Bronchospasm, cough, dyspnea, hyperventilation, hypoventilation (rebound), tachypnea

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Agitation (emergence), prolonged QT interval on ECG (premature neonates), second degree atrioventricular block (premature neonates)

Contraindications

Hypersensitivity to doxapram or any component of the formulation; significant cardiovascular impairment (eg, uncompensated heart failure, severe coronary artery disease); severe hypertension (including severe hypertension associated with hyperthyroidism or pheochromocytoma); cerebral edema, cerebral vascular accident, epilepsy or other convulsive disorders, head injury; mechanical disorders of ventilation (eg, mechanical obstruction, muscle paresis, neuromuscular blockade, flail chest, pneumothorax, acute asthma, pulmonary fibrosis), pulmonary embolism (proven or suspected)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: May cause dysrhythmias; monitor for disturbances of cardiac rhythm. If sudden hypotension develops during use, discontinue. Increases in blood pressure are generally modest; use is contraindicated in patients with severe hypertension.

• CNS stimulation: May cause severe CNS stimulation, including seizures; antiseizure medications (as well as oxygen and resuscitative equipment) should be available to manage potential excessive CNS stimulation.

Disease-related concerns:

• Cerebrovascular disease: Use with caution in patients with cerebrovascular 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: Do not use in patients on mechanical ventilation. Use with caution in treating pulmonary disease; a pressor effect on pulmonary circulation may result in a fall in arterial pO2. If sudden dyspnea develops during use, discontinue. Doxapram causes patients to increase the work of breathing; therefore, do not increase the rate of infusion in an attempt to lower the pCO2 in severely-ill COPD patients.

Concurrent drug therapy issues:

• MAO inhibitors (MAOIs): Use caution with coadministration; additive pressor effect may occur.

• Sympathomimetics: Use caution with coadministration; additive pressor effect may occur.

• 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 to decrease the risk of ventricular tachycardia or ventricular fibrillation.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Other warnings/precautions:

• Administration: Avoid extravasation; doxapram may cause thrombophlebitis or local skin irritation. Hemolysis may result from rapid infusion.

• Appropriate use: Adequate airway required prior to use; consider airway protection in case of vomiting. Resuscitative equipment (in addition to antiseizure medications and oxygen) should be readily available; doxapram alone may not be sufficient to stimulate spontaneous breathing or provide sufficient arousal. Doxapram is neither an antagonist to skeletal muscle relaxants nor an opioid antagonist. Use with caution in patients with hypermetabolic states (eg, hyperthyroidism, pheochromocytoma).

Warnings: Additional Pediatric Considerations

Recommended doses of doxapram for treatment of neonatal apnea will deliver 5.4 to 27 mg/kg/day of benzyl alcohol; the use of doxapram should be reserved for neonates who are unresponsive to the treatment of apnea with therapeutic serum concentrations of theophylline or caffeine; monitor benzyl alcohol exposure, particularly with prolonged therapy or high doses.

Possible adverse effects on mental development (based on developmental scales and index scoring) have been reported in former premature neonates (Lando 2005, Sreenan 2001). A case-controlled trial of 80 children who weighed <1,250 g at birth (mean GA: ~26.5 weeks, corrected age at assessment: 18 months) reported a significant correlation between isolated adverse mental development and total cumulative dose of doxapram (mean: 2,233 mg [cases] vs 615 mg [controls]) and duration of therapy (mean: 45.2 days [cases] vs 19.4 days [controls]) (Sreenan 2001). Another report of 88 former premature neonates (GA <28 weeks) showed an association between doxapram therapy and lower developmental scores later in infancy and early childhood (age at assessment was 9 to 15 months corrected age) (Lando 2005).

Use with caution in premature neonates and infants; hypertension (dose related), irritability, jitteriness, erratic limb movements, excessive crying, sleep disturbances, abdominal distention, vomiting, necrotizing enterocolitis, increased gastric residuals, bloody stools, hyperglycemia, glycosuria, premature eruption of teeth, and QT prolongation resulting in heart block have been reported. Seizures have been reported in premature neonates who have additional seizure risk factors including a history of seizures, perinatal asphyxia, intracerebral hemorrhage or recent aminophylline, theophylline, or caffeine exposure.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Dopram: 20 mg/mL (20 mL) [contains benzyl alcohol]

Generic Equivalent Available: US

No

Pricing: US

Solution (Dopram Intravenous)

20 mg/mL (per mL): $3.19

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

IV: Administer IV as an intermittent bolus or as an IV infusion. Avoid rapid infusion. Avoid extravasation.

Administration: Pediatric

Parenteral: IV: Administer as an intermittent bolus or as an IV infusion. Loading doses for apnea of prematurity have been infused over 15 minutes (de Waal 2019). Avoid rapid infusion. Avoid extravasation; irritating to tissues.

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 as a respiratory stimulant in adults is limited; alternate therapies are preferred.

Medication Safety Issues
Sound-alike/look-alike issues:

Doxapram may be confused with doxazosin, doxepin, DOXOrubicin

Dopram® may be confused with DOPamine

International issues:

Doxapram may be confused with Doxinate brand name for doxylamine and pyridoxine [Italy]

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination

Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Doxapram. Risk C: Monitor therapy

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Breastfeeding Considerations

It is not known if doxapram is excreted in breast milk. The manufacturer recommends that caution be exercised when administering doxapram to nursing women.

Monitoring Parameters

Heart rate, blood pressure, deep tendon reflexes, CNS status, ECG, arterial blood gases (COPD; prior to infusion initiation and at 30-minute intervals during infusion)

Mechanism of Action

Stimulates respiration through action on peripheral carotid chemoreceptors; respiratory center in medulla is also directly stimulated as dosage is increased

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Respiratory stimulation: Single IV injection: 20 to 40 seconds.

Peak effect: Single IV injection: 1 to 2 minutes.

Duration: Single IV injection: 5 to 12 minutes.

Distribution: Vd: Neonates (GA: 24 to 32 weeks; PNA: 6 to 60 days): 7.33 ± 4.55 L/kg (Jamali 1988).

Metabolism: Extensive in the liver to active metabolite (keto-doxapram).

Half-life elimination, serum:

Neonates (GA: 24 to 32 weeks; PNA: 6 to 60 days): 8.17 ± 4.13 hours (Jamali 1988).

Adults: Mean: 3.4 hours (range: 2.4 to 4.1 hours) (Robson 1979).

Clearance: Neonates (GA: 24 to 32 weeks; PNA: 6 to 60 days): 0.7 ± 0.49 L/hour/kg (Jamali 1998).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Dopram;
  • (AU) Australia: Dopram;
  • (BE) Belgium: Dopram;
  • (CH) Switzerland: Dopram;
  • (CN) China: Doxapram;
  • (CZ) Czech Republic: Dopram;
  • (DE) Germany: Dopram;
  • (ES) Spain: Docatone;
  • (FI) Finland: Dopram;
  • (FR) France: Dopram;
  • (GB) United Kingdom: Dopram | Doxapram;
  • (IE) Ireland: Dopram | Doxapram;
  • (IN) India: Caropram;
  • (JP) Japan: Dopram;
  • (KR) Korea, Republic of: Dopram | Mopram | Tapram;
  • (KW) Kuwait: Dopram;
  • (LT) Lithuania: Dopram;
  • (LV) Latvia: Dopram;
  • (NO) Norway: Dopram;
  • (NZ) New Zealand: Dopram;
  • (PL) Poland: Dopram;
  • (PR) Puerto Rico: Dopram;
  • (QA) Qatar: Dopram;
  • (SA) Saudi Arabia: Dopram;
  • (TW) Taiwan: Dopram | Doprem
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