ALFENTA

ALFENTA- alfentanil hydrochloride injection
TAYLOR PHARMACEUTICALS

CII

Rx only

DESCRIPTION

ALFENTA (alfentanil hydrochloride) Injection is an opioid analgesic chemically designated as N-[1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide monohydrochloride (1:1) with a molecular weight of 452.98 and an n-octanol:water partition coefficient of 128:1 at pH 7.4. The structural formula of ALFENTA is:

Chemical Structure
(click image for full-size original)

ALFENTA is a sterile, non-pyrogenic, preservative free aqueous solution containing alfentanil hydrochloride equivalent to 500 µg per mL of alfentanil base for intravenous injection. The solution, which contains sodium chloride for isotonicity, has a pH range of 4-6. Each mL contains: Active: Alfentanil base 500 mcg. Inactive: Sodium Chloride 9 mg and Water for Injection Q.S.

CLINICAL PHARMACOLOGY

ALFENTA (alfentanil hydrochloride) is an opioid analgesic with a rapid onset of action.

At doses of 8-40 mcg/kg for surgical procedures lasting up to 30 minutes, ALFENTA provides analgesic protection against hemodynamic responses to surgical stress with recovery times generally comparable to those seen with equipotent fentanyl dosages.

For longer procedures, doses of up to 75 mcg/kg attenuate hemodynamic responses to laryngoscopy, intubation and incision, with recovery time comparable to fentanyl. At doses of 50-75 mcg/kg followed by a continuous infusion of 0.5-3 mcg/kg/min, ALFENTA attenuates the catecholamine response with more rapid recovery and reduced need for postoperative analgesics as compared to patients administered enflurane. At doses of 5 mcg/kg, ALFENTA provides analgesia for the conscious but sedated patient. Based on patient response, doses higher than 5 mcg/kg may be needed. Elderly or debilitated patients may require lower doses. High intrasubject and intersubject variability in the pharmacokinetic disposition of ALFENTA has been reported.

The pharmacokinetics of ALFENTA can be described as a three-compartment model with sequential distribution half-lives of 1 and 14 minutes; and a terminal elimination half-life of 90-111 minutes (as compared to a terminal elimination half-life of approximately 475 minutes for fentanyl and approximately 265 minutes for sufentanil at doses of 250 mcg). The liver is the major site of biotransformation.

ALFENTA has an apparent volume of distribution of 0.4-1 L/kg, which is approximately one-fourth to one-tenth that of fentanyl, with an average plasma clearance of 5 mL/kg/min as compared to approximately 8 mL/kg/min for fentanyl.

Only 1.0% of the dose is excreted as unchanged drug; urinary excretion is the major route of elimination of metabolites. Plasma protein binding of ALFENTA is approximately 92%.

In one study involving 15 patients administered ALFENTA with nitrous oxide/oxygen, a narrow range of plasma ALFENTA concentrations, approximately 310-340 ng/mL, was shown to provide adequate anesthesia for intra-abdominal surgery, while lower concentrations, approximately 190 ng/mL, blocked responses to skin closure. Plasma concentrations between 100-200 ng/mL provided adequate anesthesia for superficial surgery.

ALFENTA has an immediate onset of action. At dosages of approximately 105 mcg/kg, ALFENTA produces hypnosis as determined by EEG patterns; an anesthetic ED90 of 182 mcg/kg for ALFENTA in unpremedicated patients has been determined, based upon the ability to block response to placement of a nasopharyngeal airway. Based on clinical trials, induction dosage requirements range from 130-245 mcg/kg. For procedures lasting 30-60 minutes, loading dosages of up to 50 mcg/kg produce the hemodynamic response to endotracheal intubation and skin incision as comparable to those from fentanyl. A pre-intubation loading dose of 50-75 mcg/kg prior to a continuous infusion attenuates the response to laryngoscopy, intubation and incision. Subsequent administration of ALFENTA infusion administered at a rate of 0.5-3 mcg/kg/min with nitrous oxide/oxygen attenuates sympathetic responses to surgical stress with more rapid recovery than enflurane.

Requirements for volatile inhalation anesthetics were reduced by thirty to fifty percent during the first 60 minutes of maintenance in patients administered anesthetic doses (above 130 mcg/kg) of ALFENTA as compared to patients given doses of 4-5 mg/kg thiopental for anesthetic induction. At anesthetic induction dosages, ALFENTA provides a deep level of anesthesia during the first hour of anesthetic maintenance and provides attenuation of the hemodynamic response during intubation and incision.

Following an anesthetic induction dose of ALFENTA, requirements for ALFENTA infusion are reduced by 30 to 50% for the first hour of maintenance.

Patients with compromised liver function and those over 65 years of age have been found to have reduced plasma clearance and extended terminal elimination for ALFENTA, which may prolong postoperative recovery. Repeated or continuous administration of ALFENTA produces increasing plasma concentrations and an accumulation of the drug, particularly in patients with reduced plasma clearance.

Bradycardia may be seen in patients administered ALFENTA. The incidence and degree of bradycardia may be more pronounced when ALFENTA is administered in conjunction with non-vagolytic neuromuscular blocking agents or in the absence of anticholinergic agents such as atropine.

Administration of intravenous diazepam immediately prior to or following high doses of ALFENTA has been shown to produce decreases in blood pressure that may be secondary to vasodilation; recovery may also be prolonged.

Patients administered doses up to 200 mcg/kg of ALFENTA have shown no significant increase in histamine levels and no clinical evidence of histamine release.

Skeletal muscle rigidity is related to the dose and speed of administration of ALFENTA. Muscular rigidity will occur with an immediate onset following anesthetic induction dosages. Preventative measures (see WARNINGS) may reduce the rate and severity.

The duration and degree of respiratory depression and increased airway resistance usually increase with dose, but have also been observed at lower doses. Although higher doses may produce apnea and a longer duration of respiratory depression, apnea may also occur at low doses.

During monitored anesthesia care (MAC), attention must be given to the respiratory effects of ALFENTA Injection. Decreased oxygen saturation, apnea, decreased respiratory rate, and upper airway obstruction can occur. (See WARNINGS)

ALFENTA Indications and Usage

ALFENTA (alfentanil hydrochloride) is indicated:

as an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturate/nitrous oxide/oxygen.
as an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia.
as a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.
as the analgesic component for monitored anesthesia care (MAC).

SEE DOSAGE CHART FOR MORE COMPLETE INFORMATION ON THE USE OF ALFENTA.

CONTRAINDICATIONS

ALFENTA (alfentanil hydrochloride) is contraindicated in patients with known hypersensitivity to the drug or known intolerance to other opioid agonists.

WARNINGS

ALFENTA SHOULD BE ADMINISTERED ONLY BY PERSONS SPECIFICALLY TRAINED IN THE USE OF INTRAVENOUS AND GENERAL ANESTHETIC AGENTS AND IN THE MANAGEMENT OF RESPIRATORY EFFECTS OF POTENT OPIOIDS.

AN OPIOID ANTAGONIST, RESUSCITATIVE AND INTUBATION EQUIPMENT AND OXYGEN SHOULD BE READILY AVAILABLE.

BECAUSE OF THE POSSIBILITY OF DELAYED RESPIRATORY DEPRESSION, MONITORING OF THE PATIENT MUST CONTINUE WELL AFTER SURGERY.

ALFENTA (alfentanil hydrochloride) administered in initial dosages up to 20 mcg/kg may cause skeletal muscle rigidity, particularly of the truncal muscles. The incidence and severity of muscle rigidity is usually dose-related. Administration of ALFENTA at anesthetic induction dosages (above 130 mcg/kg) will consistently produce muscular rigidity with an immediate onset. The onset of muscular rigidity occurs earlier than with other opioids. ALFENTA may produce muscular rigidity that involves all skeletal muscles, including those of the neck and extremities. The incidence may be reduced by: 1) routine methods of administration of neuromuscular blocking agents for balanced opioid anesthesia; 2) administration of up to 1/4 of the full paralyzing dose of a neuromuscular blocking agent just prior to administration of ALFENTA at dosages up to 130 mcg/kg; following loss of consciousness, a full paralyzing dose of a neuromuscular blocking agent should be administered; or 3) simultaneous administration of ALFENTA and a full paralyzing dose of a neuromuscular blocking agent when ALFENTA is used in rapidly administered anesthetic dosages (above 130 mcg/kg).

The neuromuscular blocking agent used should be appropriate for the patient’s cardiovascular status. Adequate facilities should be available for postoperative monitoring and ventilation of patients administered ALFENTA. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.

PATIENTS RECEIVING MONITORED ANESTHESIA CARE (MAC) SHOULD BE CONTINUOUSLY MONITORED BY PERSONS NOT INVOLVED IN THE CONDUCT OF THE SURGICAL OR DIAGNOSTIC PROCEDURE; OXYGEN SUPPLEMENTATION SHOULD BE IMMEDIATELY AVAILABLE AND PROVIDED WHERE CLINICALLY INDICATED; OXYGEN SATURATION SHOULD BE CONTINUOUSLY MONITORED; THE PATIENT SHOULD BE OBSERVED FOR EARLY SIGNS OF HYPOTENSION, APNEA, UPPER AIRWAY OBSTRUCTION AND/OR OXYGEN DESATURATION.

Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported for other opioid analgesics, and rarely with alfentanil. Therefore when alfentanil is administered to patients who have received MAO inhibitors within 14 days, appropriate monitoring and ready availability of vasodilators and beta-blockers for the treatment of hypertension is recommended.

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