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Intravenous Dilution Guidelines

Naloxone (Narcan ®)

The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.    PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

D5W, NS

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

[2 mg] [500 ml]

Fluid restricted - Higher concentrations possible:
[4 mg] [250 ml] [Titrate]
Several protocols available.   See references below.

Background

The first version of this monograph was written several years ago (~ 1993).  Occasionally changes or updates are added based on newly available data.  Most recent update (Sept 2013):

Sample references:
[1] Source:  Irwin RS, Rippe JM. Irwin and Rippe's Intensive Care Medicine. Lippincott Williams & Wilkins, 2012. (p 1656).

A continuous naloxone infusion should be considered in patients who have a positive response but require repeated bolus doses (up to 10-20 mg in some cases) because of recurrent respiratory depression...

Preparation for continuous infusion: multiply the effective bolus dose by 6.6, and then add this quantity to 1000ml NS and infuse the solution at 100 ml/hr. Titrate to maintain adequate spontaneous ventilation without precipitating acute withdrawal.  

Extremely safe drug: Naloxone has been administered at dosages of 5.4 mg/kg bolus followed by infusion at 4 mg/kg for 23 hours in the treatment of acute spinal cord injury. http://www.ncbi.nlm.nih.gov/pubmed/1727165
[Note:  NOT effective for this indication]

Dave's summary: assuming the effective bolus dose was in the range of 1 to 10 mg or possibly higher, the preparation would be as follows:
Range:  6.6 mg to 66 mg/1000ml
10 mg/1000 ml = 2.5 mg250ml
20 mg/1000 ml = 5 mg/250 ml
30 mg/1000 ml = 7.5 mg/250 ml
40 mg/1000ml = 10 mg/250 ml

[2] Source:   Helms RA, Quan DJ (eds). Textbook of Therapeutics: Drug and Disease Management. 8th ed. Philadelphia: Lippincott Williams St Wilkins; 2006. p 82.
Naloxone has short half-life of 1 hour and its duration of action of between 30 min to up to 4 hrs is often shorter than the duration of action of the opioid.

Following reversal with bolus doses, a continous infusion of naloxone can be considered for overdoses for which repeated doses are needed for recurring toxicity.

Preparation: After reversal of respiratory depression with the bolus, the infusion is initiated at two-thirds of the bolus dose per hour. At 15 min after initiation of the infusion, half of the bolus dose is readministered. If the patient becomes symptomatic at a given rate, reverse with additional bolus doses and adjust continuous infusion rate. In adults, the naloxone concentration in D5W usually is adjusted to deliver the dose in 100 ml of solution per hour.



[3]   Source: http://www.anesthesia-analgesia.org/content/100/4/953.full
Patients were randomly assigned by the hospital’s investigational drug pharmacy to one of two groups using computer-generated random numbers. Group 1, the study group, received 0.25 µg · kg-1 · h-1 of naloxone by continuous infusion. The naloxone was administered by a continuous infusion pump “piggy-backed” into the patient’s IV catheter. The naloxone solution was prepared in the pharmacy by mixing 2 mg of naloxone in 250 mL of 0.9% saline (final concentration = 8 µg/mL).


[4] Much higher concentrations were used in syringes:     Source:  Stewart JT, Warren FW, King DT, et al: Stability of ondansetron hydrochloride and 12 medications in plastic syringes. Am J Health-Syst Pharm: 1998. 55: 2630-4.
Naloxone HCL concentration: 0.133mg/mL    
Diluent:  Sodium chloride 0.9%    (Polypropylene 35-mL syringes)
Both physically and chemically stable (no loss in potency or visible particulate formation etc) over 24hrs



[5] Product Information: NARCAN(R) injection, naloxone hcl injection. Endo Pharmaceuticals,Inc.
Dilute naloxone with normal saline (NS) or 5% dextrose in water (D5W) to a concentration of 0.004 milligrams per milliliter (mg/mL) (2 mg in 500 mL).


Stability / Miscellaneous

Dosing: Treatment of narcotic-induced respiratory depression: 0.4 to 2 mg IV / SC/ IM repeat q2 to 3 minutes prn

(if no response after 10 mg --- questionable narcotic ingestion).
IV infusion: ( 2 mg/500 ml per manufacturer)
Usual infusion rate: @ 0.4 mg/hr (100 ml/hr)-titrate to respiratory rate/ level of consciousness.

DOSAGE AND ADMINISTRATION
Naloxone Hydrochloride Injection, USP may be administered intravenously, intramuscularly, or subcutaneously. The most rapid onset of action is achieved by intravenous administration and it is recommended in emergency situations.

Since the duration of action of some opioids may exceed that of naloxone, the patient should be kept under continued surveillance and repeated doses of naloxone should be administered, as necessary.

Intravenous Infusion: Naloxone Hydrochloride Injection, USP may be diluted for intravenous infusion in 0.9% sodium chloride injection or 5% dextrose injection. The addition of 2 mg of naloxone hydrochloride in 500 mL of either solution provides a concentration of 0.004 mg/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused solution must be discarded. The rate of administration should be titrated in accordance with the patient’s response.

Naloxone Hydrochloride Injection, USP should not be mixed with preparations containing bisulfite, metabisulfite, long-chain or high molecular weight anions, or any solution having an alkaline pH. No drug or chemical agent should be added to Naloxone Hydrochloride Injection, USP unless its effect on the chemical and physical stability of the solution has first been established.

Alternatively:
Children and Adults: Continuous infusion: I.V.: If continuous infusion is required, calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen, titrate dose 0.04-0.16 mg/kg/hour for 2-5 days in children, adult dose typically 0.25-6.25 mg/hour (short-term infusions as high as 2.4 mg/kg/hour have been tolerated in adults during treatment for septic shock); alternatively, continuous infusion utilizes 2/3 of the initial naloxone bolus on an hourly basis; add 10 times this dose to each liter of D5W and infuse at a rate of 100 mL/hour; 1/2 of the initial bolus dose should be readministered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels; increase infusion rate as needed to assure adequate ventilation.

Stability:
Store at 25°C (77°F); protect from light; stable in 0.9% sodium chloride and D5W at 4 mcg/mL for 24 hours; do not mix with alkaline solutions. (Source: Lexi-drugs)

Usage in Adults:
Opioid Overdose—Known or Suspected: An initial dose of 0.4 mg to 2 mg of naloxone hydrochloride may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at 2 to 3 minute intervals. If no response is observed after 10 mg of naloxone hydrochloride have been administered, the diagnosis of opioid induced or partial opioid induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available.

Postoperative Opioid Depression: For the partial reversal of opioid depression following the use of opioids during surgery, smaller doses of naloxone hydrochloride are usually sufficient. The dose of naloxone should be titrated according to the patient’s response. For the initial reversal of respiratory depression, naloxone hydrochloride should be injected in increments of 0.1 to 0.2 mg intravenously at two to three minute intervals to the desired degree of reversal, i.e., adequate ventilation and alertness without significant pain or discomfort. Larger than necessary dosage of naloxone may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating or circulatory stress.

Repeat doses of naloxone may be required within one to two hour intervals depending upon the amount, type (i.e., short or long acting) and time interval since last administration of opioid. Supplemental intramuscular doses have been shown to produce a longer lasting effect.

Septic Shock: The optimal dosage of Naloxone or duration of therapy for the treatment of hypotension in septic shock patients has not been established


Source: [package insert]
Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
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