Nalmefene Hydrochloride Side Effects

ADVERSE REACTIONS Adverse event information was obtained following administration of nalmefene hydrochloride injection to 152 normal volunteers and in controlled clinical trials to 1127 patients for the treatment of opioid overdose or for postoperative opioid reversal.

Nalmefene was well tolerated and showed no serious toxicity during experimental administration to healthy individuals, even when given at 15 times the highest recommended dose.

In a small number of subjects, at doses exceeding the recommended nalmefene hydrochloride injection dose, nalmefene produced symptoms suggestive of reversal of endogenous opioids, such as have been reported for other narcotic antagonist drugs.

These symptoms (nausea, chills, myalgia, dysphoria, abdominal cramps, and joint pain) were usually transient and occurred at very low frequency.

Such symptoms of precipitated opioid withdrawal at the recommended clinical doses were seen in both postoperative and overdose patients who were later found to have had histories of covert opioid use.

Symptoms of precipitated withdrawal were similar to those seen with other opioid antagonists, were transient following the lower doses used in the postoperative setting, and more prolonged following the administration of the larger doses used in the treatment of overdose.

Tachycardia and nausea following the use of nalmefene in the postoperative setting were reported at the same frequencies as for naloxone at equivalent doses.

The risk of both these adverse events was low at doses giving partial opioid reversal and increased with increases in dose.

Thus, total doses larger than 1.0 µg/kg in the postoperative setting and 1.5 mg/70 kg in the treatment of overdose are not recommended.

Relative Frequencies of Common Adverse Reactions With an Incidence Greater than 1% (all patients, all clinical settings) Adverse Event Nalmefene Naloxone Placebo N=1127 N=369 N=77 Nausea 18% 18% 6% Vomiting 9% 7% 4% Tachycardia 5% 8% - Hypertension 5% 7% - Postoperative pain 4% 4% N/A Fever 3% 4% - Dizziness 3% 4% 1% Headache 1% 1% 4% Chills 1% 1% - Hypotension 1% 1% - Vasodilatation 1% 1% - Incidence less than 1% CARDIOVASCULAR: Bradycardia, arrhythmia DIGESTIVE: Diarrhea, dry mouth NERVOUS SYSTEM: Somnolence, depression, agitation, nervousness, tremor, confusion, withdrawal syndrome, myoclonus RESPIRATORY: Pharyngitis SKIN: Pruritus UROGENITAL: Urinary retention The incidence of adverse events was highest in patients who received more than the recommended dose of nalmefene hydrochloride injection.