REVEX is indicated for the complete or partial reversal of opioid drug effects,
including respiratory depression, induced by either natural or synthetic opioids.
REVEX is indicated in the management of known or suspected opioid overdose.
DOSAGE AND ADMINISTRATION
Important Information - Dosage Forms
REVEX is supplied in two concentrations that can be identified by their color coded container labels: a concentration suitable for postoperative use (100 µg/mL) in a blue labeled ampul containing ONE (1) mL and a concentration suitable for the management of overdose (1 mg/mL, 10 times as concentrated, 20 times as much drug) in a green labeled ampul containing TWO (2) mL. Proper steps should be taken to prevent use of the incorrect concentration.
REVEX should be titrated to reverse the undesired effects of opioids. Once adequate reversal has been established, additional administration is not required and may actually be harmful due to unwanted reversal of analgesia or precipitated withdrawal.
Duration of Action
The duration of action of REVEX is as long as most opioid analgesics. The apparent
duration of action of REVEX will vary, however, depending on the half-life and
plasma concentration of the narcotic being reversed, the presence or absence
of other drugs affecting the brain or muscles of respiration, and the dose of
REVEX administered. Partially reversing doses of REVEX (1 µg/kg) lose
their effect as the drug is redistributed through the body, and the effects
of these low doses may not last more than 30-60 minutes in the presence of persistent
opioid effects. Fully reversing doses (1 mg/70 kg) have been shown to last many
hours in both experimental and clinical studies, but may complicate the management
of patients who are in pain, at high cardiovascular risk, or who are physically
dependent on opioids.
The recommended doses represent a compromise between a desirable controlled reversal and the need for prompt response and adequate duration of action. Using higher dosages or shorter intervals between incremental doses is likely to increase the incidence and severity of symptoms related to acute withdrawal such as nausea, vomiting, elevated blood pressure, and anxiety.
Patients Tolerant to or Physically Dependent on Opioids
REVEX may cause acute withdrawal symptoms in individuals who have some degree of tolerance to and dependence on opioids. These patients should be closely observed for symptoms of withdrawal following administration of the initial and subsequent injections of REVEX. Subsequent doses should be administered with intervals of at least 2-5 minutes between doses to allow the full effect of each incremental dose of REVEX to be reached.
Recommended Doses for Reversal of Postoperative Opioid Depression
Use 100 µg/mL dosage strength (blue label) and see Table 2 for initial
The goal of treatment with REVEX in the postoperative setting is to achieve
reversal of excessive opioid effects without inducing a complete reversal and
acute pain. This is best accomplished with an initial dose of 0.25 µg/kg
followed by 0.25 µg/kg incremental doses at 2-5 minute intervals, stopping
as soon as the desired degree of opioid reversal is obtained. A cumulative total
dose above 1.0 µg/kg does not provide additional therapeutic effect.
Table 2: Reversal of Postoperative Opioid Depression
| Body Weight
|| mL of REVEX
100 µg/mL Solution
In cases where the patient is known to be at increased cardiovascular risk,
it may be desirable to dilute REVEX 1:1 with saline or sterile water and use
smaller initial and incremental doses of 0.1 µg/kg.
Management of Known or Suspected Opioid Overdose
Use 1.0 mg/mL dosage strength (green label).
The recommended initial dose of REVEX for non-opioid dependent patients is
0.5 mg/70 kg. If needed, this may be followed by a second dose of 1.0 mg/70
kg, 2-5 minutes later. If a total dose of 1.5 mg /70 kg has been administered
without clinical response, additional REVEX (nalmefene hydrochloride injection)
is unlikely to have an effect. Patients should not be given more REVEX than
is required to restore the respiratory rate to normal, thus minimizing the likelihood
of cardiovascular stress and precipitated withdrawal syndrome.
If there is a reasonable suspicion of opioid dependency, a challenge dose of
REVEX 0.1 mg/70 kg should be administered initially. If there is no evidence
of withdrawal in 2 minutes, the recommended dosing should be followed.
REVEX had no effect in cases where opioids were not responsible for sedation and hypoventilation. Therefore, patients should only be treated with REVEX when the likelihood of an opioid overdose is high, based on a history of opioid overdose or the clinical presentation of respiratory depression with concurrent pupillary constriction.
REVEX is the longest acting of the currently available parenteral opioid antagonists. If recurrence of respiratory depression does occur, the dose should again be titrated to clinical effect using incremental doses to avoid over-reversal.
Hepatic and Renal Disease
Hepatic disease and renal failure substantially reduce the clearance of nalmefene
(see Pharmacokinetics). For single episodes of opioid antagonism, adjustment
of REVEX dosage is not required. However, in patients with renal failure, the
incremental doses should be delivered slowly (over 60 seconds) to minimize the
hypertension and dizziness reported following the abrupt administration of nalmefene
to such patients.
Loss of Intravenous Access
Should intravenous access be lost or not readily obtainable, a pharmacokinetic
study has shown that a single dose of REVEX should be effective within 5-15
minutes after intramuscular or subcutaneous doses of 1.0 mg. (See Pharmacokinetics.)
Safety and Handling
REVEX is distributed in sealed ampuls which represent no known risk to health
care workers. As with all parenterals, care should be taken to prevent the generation
and inhalation of aerosols during preparation and use. Dermal absorption of
spilled REVEX should be prevented by prompt removal of contaminated clothing
and rinsing the skin thoroughly with cool water.
Parenteral drug products should be inspected visually for particulate matter
and discoloration prior to administration, whenever solution and container permit.
REVEX (nalmefene hydrochloride injection) is available in the following presentations:
An ampul containing 1 mL of 100 µg/mL nalmefene base (Blue Label) Box
of 10 (NDC 10019-315-21)
An ampul containing 2 mL of 1 mg/mL nalmefene base (Green Label) Box of 10 (NDC 10019-311-22)
Store at controlled room temperature.
Manufactured for Baxter Healthcare Corporation, Deerfield, IL 60015 USA. Manufactured
by: Taylor Pharmaceuticals, Decatur, IL 62525. For Product Inquiry 1 800 ANA