Doxapram is an analeptic agent. It stimulates the respiratory muscles resulting in an increase in the tidal volume and respiratory rate.

Doxapram Uses:

• 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, as a respiratory stimulant, the use of doxapram in adults is limited; other therapies (Aminophylline) are preferred.

Adult dose:

 Note:

• Although drug manufacturer's dosing recommendations are presented for these FDA-approved indications, the use of doxapram has largely been replaced by alternate preferred drugs.

Doxapram Dose in Respiratory depression following anesthesia: 

• Intermittent injection:

  • Initial: 0.5 to 1 mg/kg;
  • may be repeated every five minutes (only in patients who demonstrate initial response)
  • maximum single injection dose: 1.5 mg/kg;
  • maximum total dose: 2 mg/kg

• IV infusion:

  • Initial: Reduce to 1 to 3 mg/minute after sufficient response or the occurrence of any negative effects at 5 mg/minute.
  • maximum total dose: 4 mg/kg

Doxapram Dose in the treatment of Drug-induced CNS depression:

• Intermittent injection:

  • Initial: Priming dose of 1 to 2 mg/kg;
  • After every five minutes, repeat (only in patients who demonstrate initial response)
  • Maximum: 3000 mg per day, repeatable every 1 to 2 hours (until sustained consciousness).
  • May repeat in 24 hours if necessary.

• IV infusion:

  • Initial: Priming dose of 1 to 2 mg/kg repeated every 5 minutes.
  • If there is no reaction, wait one to two hours before trying the first dose again.
  • Start the infusion at 1 to 3 mg/minute (depending on the size of the patient and the degree of CNS depression) if there is evidence of stimulation; stop the infusion if the patient starts to wake up.
  • The infusion should not be continued for >2 hours.
  • May restart infusion as described above, including bolus, after rest of 30 minutes to 2 hours;
  • maximum: 3000 mg/day.

Doxapram Dose in the treatment of Acute hypercapnia secondary to COPD:

• IV infusion:
  • Initial: Initiate infusion at 1 to 2 mg/minute (depending on the size of the patient as well as the depth of CNS depression);
  • may increase to a maximum rate of 3 mg/minute;
  • The infusion should not be continued for >2 hours.
  • Additional infusions are not recommended (per manufacturer).

Dose in children:

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manufacturer's dosing recommendations are presented for these FDA-approved indications, use of doxapram has largely been replaced by other preferred drugs.

Doxapram Dose in the treatment of Drug-induced CNS depression:

• Children ≥12 years and Adolescents:

  • IV: Initial:

    • A priming dose of 1 to 2 mg/kg; repeat after every 5 minutes;
    • The dose may be repeated at every 1 to 2-hour intervals (until sustained consciousness);
    • if relapse occurs may resume repeat doses every 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 administered to patients who showed a response to the initial dose.

  • IV infusion:

    • Initial: Priming dose of 1 to 2 mg/kg repeated every 5 minutes.
    • If there is no reaction, wait one to two hours before trying the first dose again.
    • Start the infusion at 1 to 3 mg/minute (depending on the size of the patient and the degree of CNS depression) if there is evidence of stimulation; stop the infusion if the patient starts to wake up.
    • The infusion should not be continued for >2 hours.
    • May restart infusion as described above, including bolus, after an interval of 30 minutes to 2 hours;
    • maximum daily dose: 3,000 mg/day.

Doxapram Dose in respiratory depression following anesthesia:

• Children ≥12 years and Adolescents:

  • IV:

    • Initial: 0.5 to 1 mg/kg;
    • The dose may be repeated every 5-minute intervals;
    • The maximum total dose is 2 mg/kg

  • Continuous IV infusion:

    • Initial: 5 mg/minute until appropriate response or adverse effects seen; decrease to 1 to 3 mg/minute;
    • maximum total dose: 4 mg/kg (in an average adult, about ~300 mg total dose)

Pregnancy Risk Factor B

• Animal reproduction studies have not shown any adverse events.

Doxapram use during breastfeeding:

• It is unknown if doxapram can be found in breast milk.
• Doxapram should not be administered to nursing mothers.

Renal dose:

Doxapram Dose in Kidney disease:

• The manufacturer's labelling does not mention dosage changes (this has not been researched); however, in cases of severe impairment, proceed with caution because changed pharmacokinetics may occur.

Doxapram Dose in Liver disease:

• The manufacturer's labelling does not mention dosage changes (this has not been researched); however, in cases of severe impairment, proceed with caution because changed pharmacokinetics may occur.

Side effects of Doxapram:

• 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

Contraindications to Doxapram:

• Hypersensitivity/Allergy to doxapram or any component of the formulation;
• Significant cardiovascular impairment (eg uncompensated cardiac failure, severe coronary disease)
• severe hypertension (including hyperthyroidism and pheochromocytoma)
• cerebral edema,
• cerebral vascular accident,
• Epilepsy and other convulsive disorders
• Head injury
• Mechanical disorders of ventilation include mechanical obstruction, muscle paresis and neuromuscular blockade. Flail chest, pneumothorax. Acute asthma, pulmonary Fibrosis.
• Pulmonary embolism (proven, suspected or suspected)

Warnings and precautions

• Cardiovascular effects

  • Dysrhythmias can occur; be aware of irregularities in your cardiac rhythm.
  • If sudden hypotension develops during use, discontinue.
  • Generally speaking, blood pressure increases are modest.
  • Patients with severe hypertension should not use this medication.

• Stimulation of the CNS:

  • May cause severe CNS stimulation, including seizures;
  • To manage excessive CNS stimulation, anticonvulsants should be available.

• Cerebrovascular disease

  • Patients with cerebrovascular diseases should be cautious
  • Hyperventilation results in a decrease in pCO2, which causes cerebral vasoconstriction, and lower circulation.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

• Renal impairment

  • Patients with impaired renal function should be cautious.

• Respiratory disease

  • Patients on mechanical ventilation should not be exposed to this product.
  • Take care when treating pulmonary diseases. A pressor effect on the circulation could cause a drop in arterial pO2.
  • If sudden dyspnea develops during use, discontinue.
  • Doxapram can cause patients to increase their work of breathing.
  • Therefore, don't increase the rate at which you infuse Doxapram to try to lower the pCO for severely COPD patients.

Doxapram: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

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)

How to administer Doxapram?

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

Mechanism of action of Doxapram:

• Stimulates respiration through the stimulation of peripheral carotid and chemoreceptors.
• The respiratory center in your medulla can also be directly stimulated when the dosage is increased.

The beginning of action:

• Respiratory stimulation: One IV injection: In 20-40 seconds

Peak effect:

• Single IV injection: 1 to 2 minutes

Duration:

• Single IV injection: 5 to 12 minutes

Metabolism:

• Extensive in the liver to an active metabolite (keto-doxapram)

Half-life elimination, serum:

• Neonates, premature: 6.6 to 12 hours
• Adults: Mean: 3.4 hours (range: 2.4 to 4.1 hours)
• Clearance: Neonates, premature: 0.44 to 0.7 L/hour/kg

International Brands of Doxapram:

• Dopram
• Analetapram
• Boda
• Caropraml
• Dopram
• Mopram
• Tapram

Doxapram Brand Names in Pakistan:

No Brands Available in Pakistan.