DOSAGE AND ADMINISTRATION
NOTE: CONTAINS BENZYL ALCOHOL (SEE PRECAUTIONS)
In Postanesthetic Use
Table I. Dosage for postanesthetic use –I.V. and infusion.
| Recommended || Maximum dose per || Maximum |
| Dosage || single injection || total dose
| I.V. |
| Administration || mg/kg || mg/kg || mg/kg |
|Single Injection ||0.5-1 ||1.5 ||1.5 |
|Repeat Injections |
(5 min. intervals)
|0.5-1 ||1.5 ||2 |
|Infusion ||0.5-1 ||— ||4 |
BY I.V. INJECTION
(See Table I. Dosage for postanesthetic use (I.V. and infusion.)
The recommended dose for I.V. administration is 0.5 to 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.
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.
| METHOD ONE || METHOD TWO |
| Priming dose single/repeat || Rate of intermittent |
| I.V. injection || I.V. infusion |
| Level of Depression |
| mg/kg || mg/kg/hr |
||1 ||1-2 |
||2 ||2-3 |
Using Single and/or Repeat Single I.V. Injections
a. 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.
b. Repeat same dose q1 to 2h until patient wakens. Watch for relapse into unconsciousness or development of respiratory depression, since doxapram does not affect the metabolism of CNS-depressant drugs.
c. If relapse occurs, resume injections q1 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, using assisted or automatic respiration if necessary.
d. Repeat procedure the following day until patient breathes spontaneously and sustains desired level of consciousness, or until maximum dosage (3 grams) is given.
e. Repetitive doses should be administered only to patients who have shown response to the initial dose.
f. Failure to respond appropriately indicates the need for neurologic evaluation for a possible central nervous system source of sustained coma.
By Intermittent I.V. Infusion
a. Give priming dose as in Method One.
b. If patient wakens, watch for relapse; if no response, continue general supportive treatment for 1 to 2 hours and repeat priming dose of doxapram. If some respiratory stimulation occurs, prepare I.V. infusion by adding 250 mg of doxapram (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 if patient begins to waken or at end of 2 hours.
c. Continue supportive treatment for 1/2 to 2 hours and repeat Step b.
d. Do not exceed 3 grams/day.
Chronic Obstructive Pulmonary Disease Associated with Acute Hypercapnia
a. One vial of doxapram (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 (1/2 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’s administration and at least every half hour during the two hours of infusion to insure against the insidious development of CO2-RETENTION AND ACIDOSIS. Alteration of oxygen concentration or flow rate may necessitate adjustment in the rate of doxapram infusion.
b. Predictable blood gas patterns are more readily established with a continuous infusion of doxapram. If the blood gases show evidence of deterioration, the infusion of doxapram should be discontinued.
c. ADDITIONAL INFUSIONS BEYOND THE SINGLE MAXIMUM TWO HOUR ADMINISTRATION PERIOD ARE NOT RECOMMENDED.
Doxapram hydrochloride is compatible with 5% and 10% dextrose in water or normal saline.
ADMIXTURE OF DOXAPRAM WITH ALKALINE SOLUTIONS SUCH AS 2.5% THIOPENTAL SODIUM, SODIUM BICARBONATE, FUROSEMIDE, OR AMINOPHYLLINE WILL RESULT IN PRECIPITATION OR GAS FORMATION.
Doxapram is also not compatible with ascorbic acid, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefuroxime sodium, folic acid, dexamethasone disodium phosphate, diazepam, hydrocortisone sodium phosphate, methylprednisolone sodium, or hydrocortisone sodium succinate.
Admixture of doxapram and ticarcillin disodium results in an 18% loss of doxapram in 3 hours. When doxapram is mixed with minocycline hydrochloride, there is a loss of 8% of doxapram in 3 hours and a 13% loss of doxapram in 6 hours.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.