NALOXONE & NALMEFENE

Prepared by : Areen Zraikah Dana Fatayer

Pharmacology: Naloxone and nalmefene are pure

opioid antagonists that competitively block mu, kappa, and delta opiate receptors within the CNS.

They have no opioid agonist properties and can be given safely in large doses without producing respiratory or CNS depression.

_ Naloxone, a synthetic N-allyl derivative of oxymorphone.

_ Undergoes extensive first-pass

metabolism and is not effective orally.

_ Given SC, IM,IV and even endotracheally.

_ After IV administration, opioid antagonism occurs within 1-2 minutes and persists for approximately 1-4 hours.

_ Nalmefene, an injectable methylene analog of naltrexone .

_ It is 4 times more potent than naloxone at mu

receptors and slightly more potent at kappa receptors.

_ It has a longer elimination half-life ranging from appr11

hours after IV dosing and a duration of action of 4 hours .

_ The prolonged effects of nalmefene are related to the slow dissociation from the opioid receptor .

Indications

A. Reversal of acute opioid intoxication manifested by coma, respiratory depression, or hypotension.

B. Empiric therapy for stupor or coma suspected to be caused by opioid overdose.

C. Anecdotal reports suggest that high-dose naloxone may partially reverse the CNS and respiratory depression associated with clonidine, ethanol, Benzodiazepine, or valproic acid overdoses, although these effects are inconsistent.

Contraindications:

In patients with a known hypersensitivity to either naloxone or nalmefene (may have cross-sensitivity).

Adverse effects: Human studies have documented an

excellent safety record for both.

1 -Use in opiate-dependent patients may precipitate acute withdrawal syndrome .

2 -Pulmonary edema or ventricular fibrillation occasionally has occurred shortly after naloxone administration in opioid-intoxicated patients. Pulmonary edema has also been associated with postanesthetic use of naloxone, especially when catecholamines and large fluid volumes have been administered .Pulmonary edema has been reported after IV nalmefene..

3 -Reversing the sedative effects of an opioid may amplify the toxic effects of other drugs .

4-Seizures have been associated with nalmefene use in animal studies but have

not been reported in humans .

5 -There has been one case report of hypertension after naloxone administration in a patient with clonidine overdose .

Use in pregnancy: -FDA category B

- Naloxone- or nalmefene -induced drug withdrawal syndrome may precipitate labor in an opioid-dependent

mother .

Drug or laboratory interactions:Naloxone and nalmefene antagonize the analgesic effect of opioids.

Dosage and method of administration for suspected opioid-induced coma:

Naloxone: _ Administer 0.4-2 mg IV; repeat at 2- to 3-

minute intervals until desired response is

achieved ._ Titrate carefully in opioid-dependent patients

(start at 0.05 mg). _ The dose for children is the same as that for

adults.

Caution:_ Resedation can occur when the naloxone

wears off in 1-2 hours.

_ Repeated doses of naloxone may be required to maintain reversal of the effects of opioids with prolonged elimination half-lives (eg,methadone) or sustained-release formulations or when packets or vials have been ingested.

Infusion:_ Give 0.4-0.8 mg/h in normal saline or 5%

dextrose, titrated to clinical effect (in infants, start with 0.04-0.16 mg/kg/h).

_ Another method is to estimate two-thirds of

the initial dose needed to awaken the patient and give that amount each hour.

Formulations: _ Naloxone hydrochloride (Narcan): 0.02,

0.4, or 1 mg/mL; 1-, 2-, or 10-mL syringes, ampules,or vials .

_ The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 30 mg (three vials, 1 mg/mL, 10 mL each, or equivalent).

Nalmefene:._In a non-opioid-dependent adult, give an initial dose of 0.5

mg/70 kg, followed by

1.0 mg/70 kg 5 minutes later. No added benefit of dosage higher than 1.5 mg/70 kg .

_If opioid dependency is suspected, give a challenge dose of 0.1 mg/70 kg, followed by a

2-minute wait for signs or symptoms of opioid withdrawal (nausea, chills, myalgia, dysphoria, abdominal cramps, joint pain). If there is no indication of withdrawal, give standard doses .

_ The effect of the drug may be prolonged in patients with end-stage renal failure or hepatic disease.

_It has been shown to be safe and effective in reversing procedural sedation in children when given in postoperative incremental doses of 0.25 mcg/kg every 5 minutes to a maximum total dose of 1 mcg/kg.

_As with naloxone, the total dose required to reverse the effects of the opioid is highly variable.

Caution:

Smaller doses of nalmefene may have a shorter duration because of rapid redistribution of the

drug out of the brain .

Fully reversing doses (1.5 mg in a 70-kg person) have been shown to last several hours. However, this may not be long enough for patients who have overdosed on a

long-acting opioid such as methadone or have ingested a drug-containing condom or packet with unpredictable breakage and absorption.

Formulations: Nalmefene hydrochloride (Revex): 100 mcg in 1-mL ampules ; 1 mg/mL in 2-ml vials ; syringes containing 2 mL of 1 mg/mL nalmefene .

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 16 mg (eight vials, 1 mg/mL, 2 ml each, or equivalent).

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