Nalmefene Hydrochloride

(BANM, rINNM)
Synonyms: Hidrocloruro de nalmefeno; Nalméfène, Chlorhydrate de; Nalmefeni Hydrochloridum; Nalmetrene Hydrochloride.
Cyrillic synonym: Налмефена Гидрохлорид.

💊 Chemical information

Chemical formula: C21H25NO3,HCl = 375.9.
CAS — 58895-64-0.

💊 Adverse Effects

Nausea, vomiting, tachycardia, hypertension, fever, and dizziness have been reported with therapeutic doses of nalmefene. At higher doses or in patients later found to be physically dependent on opioids, symptoms suggestive of opioid withdrawal have been noted; these have included abdominal cramps, chills, dysphoria, myalgia, and joint pain.

💊 Precautions

As for Naloxone. Incremental doses of nalmefene should be given slowly in patients with renal impairment.

💊 Pharmacokinetics

Nalmefene is absorbed after oral doses but bioavailability is not complete owing to significant first-pass metabolism. It is metabolised in the liver, mainly to the inactive glucuronide, and is excreted in the urine. Some of the dose is excreted in the faeces and it may undergo enterohepatic recycling. The plasma elimination half-life is reported to be about 10 hours.
1. Dixon R, et al. Nalmefene: intravenous safety and kinetics of a new opioid antagonist. Clin Pharmacol Ther 1986; 39: 49–53
2. Dixon R, et al. Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist. J Clin Pharmacol 1987; 27: 233–9
3. Frye RF, et al. The effect of age on the pharmacokinetics of the opioid antagonist nalmefene. Br J Clin Pharmacol 1996; 42: 301–6
4. Frye RF, et al. Effects of liver disease on the disposition of the opioid antagonist nalmefene. Clin Pharmacol Ther 1997; 61: 15–23.

💊 Uses and Administration

Nalmefene is a derivative of naltrexone and is a specific opioid antagonist with actions and uses similar to those of naloxone, but with a longer duration of action. It is given as the hydrochloride but doses are expressed in terms of the base. Nalmefene hydrochloride 111 micrograms is equivalent to about 100 micrograms of nalmefene. It is usually given intravenously for a rapid onset of action; subcutaneous or intramuscular administration is also effective but has a slower onset. Nalmefene has also been given orally. For the reversal of postoperative central depression due to the use of opioids, nalmefene is given intravenously, at a concentration of 100 micrograms/mL, in an initial dose of 250 nanograms/kg. Further doses of 250 nanograms/kg may be given at intervals of 2 to 5 minutes until the desired level of opioid reversal is reached; cumulative doses above 1 microgram/kg do not provide additional benefit. In patients with an increased cardiovascular risk a concentration of 50 micrograms/mL and doses and increments of 100 nanograms/kg are recommended. In the management of known or suspected opioid overdosage, nalmefene is given intravenously at a concentration of 1 mg/mL. An initial dose of 500 micrograms per 70 kg is recommended, followed by a second dose of 1 mg per 70 kg after 2 to 5 minutes if necessary. If a total dose of 1.5 mg per 70 kg is not effective then additional doses are unlikely to have an effect. If the patient is suspected of being physically dependent on opioids an initial test dose of 100 micrograms per 70 kg is recommended; if there is no evidence of withdrawal symptoms within 2 minutes the usual dosage may be used. Although nalmefene has a longer duration of action than naloxone, all patients should be closely observed and if respiratory depression does recur, the dose of nalmefene should be titrated as above to avoid overreversal of opioid effects.

Alcohol withdrawal and abstinence.

For mention of the use of nalmefene in the adjunctive management of patients with alcohol dependence, see under Naltrexone.

Pruritus.

It has been suggested that because central opioid receptors modulate itch, an opioid antagonist might be useful in pruritus. A systematic review1 found that opioid antagonists are effective in opioid-induced pruritus, and a number have also been reported to be of benefit in pruritus of other causes. Rapid improvement of severe pruritus was reported after a single oral dose of nalmefene 10 or 20 mg in a double-blind study of 80 patients with either chronic urticaria or atopic dermatitis.2 Pruritus was almost completely eliminated in up to 60% of patients receiving nalmefene. Adverse effects occurred in 67% of patients and included dizziness or lightheadedness, fatigue, and nausea. In another study,3 14 patients with resistant pruritus secondary to cholestatic liver disease were treated with oral nalmefene for 2 to 26 months. The initial dose was 2 mg twice daily and the dose was increased gradually as necessary. Although 13 of the patients reported some amelioration of pruritus, 5 found that increasing doses were required to produce any benefit, and in 3 tolerance appeared to develop. Continuous infusion of naloxone 200 nanograms/kg per minute was reported to reduce perception of pruritus and scratching activity in a double-blind study of 29 patients with pruritus due to cholestasis,4 although the role of continuous infusion in longterm management may be limited. Benefit has been reported with oral naltrexone 50 mg daily in pruritus of various origins,5 as well as in patients with cholestatic pruritus.6,7 In uraemic pruritus, conflicting results have been reported;8,9 a subsequent study10 suggested that naltrexone might be of benefit in selected patients.
1. Kjellberg F, Tramèr MR. Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials. Eur J Anaesthesiol 2001; 18: 346–57
2. Monroe EW. Efficacy and safety of nalmefene in patients with severe pruritus caused by chronic urticaria and atopic dermatitis. J Am Acad Dermatol 1989; 21: 135–6
3. Bergasa NV, et al. Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. Hepatology 1998; 27: 679–84
4. Bergasa NV, et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. Ann Intern Med 1995; 123: 161–7
5. Metze D, et al. Efficacy and safety of naltrexone, an oral opiate receptor antagonist, in the treatment of pruritus in internal and dermatological diseases. J Am Acad Dermatol 1999; 41: 533–9
6. Wolfhagen FH, et al. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology 1997; 113: 1264–9
7. Terg R, et al. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebocontrolled study. J Hepatol 2002; 37: 717–22
8. Peer G, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet 1996; 348: 1552–4
9. Pauli-Magnus C, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study. J Am Soc Nephrol 2000; 11: 514–9
10. Legroux-Crespel E, et al. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology 2004; 208: 326–30.

💊 Preparations

Proprietary Preparations

Mex.: Nocarex; USA: Revex.
Published December 04, 2018.