Alfenta

Name: Alfenta

Warnings

Black Box Warnings

Therapy exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing therapy, and monitor all patients regularly for the development of these behaviors and conditions

Contraindications

Hypersensitivity

Increased intracranial pressure

Severe respiratory depresssion

Cautions

Use caution in bradycardia, compromised cardiac reserve, head injury, hypothyroidism, increased ICP, intracranial lesions, renal impairment, respiratory impairment, obesicty, history of drug abuse

Concurrent administration of benzodiazepine or neuromuscular blocker will decrease chest wall rigidity

Should be administered by trained individuals

In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

May cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

Therapy may increase frequency of seizures in patients with seizure disorders and in other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; monitor closely

Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

Muscle rigidity occurring during induction of can be treated by decreasing rate or discontinuing infusion of drug or by administering a neuromuscular blocking agent; neuromuscular blocking agents used should be compatible with patient's cardiovascular status

Not to be administered into same IV tubing with blood due to potential inactivation by nonspecific esterases in blood products

Proper placement of needle or catheter in epidural space should be verified before drug is injected to assure that unintentional intravascular or intrathecal administration does not occur; unintentional intravascular injection of sufentanil could result in a potentially serious overdose, including acute truncal muscular rigidity and apnea; unintentional intrathecal injection of sufentanil/bupivacaine epidural doses and volume could produce effects of high spinal anesthesia including prolonged paralysis and delayed recovery; if analgesia is inadequate, placement and integrity of catheter should be verified prior to administration of any additional epidural medications; administer epidurally by slow injection

Bradycardia may occur; monitor heart rate during dosage initiation and titration; responsive to ephedrine or anticholinergic drugs

Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

Pharmacology

Mechanism of Action

Narcotic agonist analgesic; increases pain threshold, inhibits ascending pain pathways, alters pain perception

Pharmacokinetics

Half-life: 5.33-8.75 hr (prematures, newborns); 40-60 min (children); 83-97 min (adults)

Onset: Immediate

Duration: 30-60 min

Vd: 1 L/kg (premature, newborns); 0.163-0.48 L/kg (children); 0.46 L/kg (adults)

Peak Plasma: distributed in decreasing order of concentration into skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain

Bioavailability: Varies

Metabolism: liver (hepatic P450 enzyme CYP3A4), CNS, kidneys, lungs, and placenta (conjugation with glucuronic acid, hydrolysis, oxidation, N-dealkylation)

Excretion: urine, feces

Alfenta Overview

Alfenta is a brand name medication included in a group of medications called Opioid anesthetics. For more information about Alfenta see its generic Alfentanil

Alfenta®

CII

Rx only

Indications and Usage for Alfenta

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.

Precautions

DELAYED RESPIRATORY DEPRESSION, RESPIRATORY ARREST, BRADYCARDIA, ASYSTOLE, ARRHYTHMIAS AND HYPOTENSION HAVE ALSO BEEN REPORTED. THEREFORE, VITAL SIGNS MUST BE MONITORED CONTINUOUSLY.

General

The initial dose of Alfenta (Alfentanil hydrochloride) should be appropriately reduced in elderly and debilitated patients. The effect of the initial dose should be considered in determining supplemental doses. In obese patients (more than 20% above ideal total body weight), the dosage of Alfenta should be determined on the basis of lean body weight.

In one clinical trial, the dose of Alfenta required to produce anesthesia, as determined by appearance of delta waves in EEG, was 40% lower in geriatric patients than that needed in healthy young patients.

In patients with compromised liver function and in geriatric patients, the plasma clearance of Alfenta may be reduced and postoperative recovery may be prolonged.

Induction doses of Alfenta should be administered slowly (over three minutes). Administration may produce loss of vascular tone and hypotension. Consideration should be given to fluid replacement prior to induction.

Diazepam administered immediately prior to or in conjunction with high doses of Alfenta may produce vasodilation, hypotension and result in delayed recovery.

Bradycardia produced by Alfenta may be treated with atropine. Severe bradycardia and asystole have been successfully treated with atropine and conventional resuscitative methods.

The hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required should be considered in the selection of a neuromuscular blocking agent.

Following an anesthetic induction dose of Alfenta, requirements for volatile inhalation anesthetics or Alfenta infusion are reduced by 30 to 50% for the first hour of maintenance.

Alfenta infusions should be discontinued at least 10-15 minutes prior to the end of surgery during general anesthesia. During administration of Alfenta for Monitored Anesthesia Care (MAC), infusions may be continued to the end of the procedure.

Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists such as naloxone. Because the duration of respiratory depression produced by Alfenta may last longer than the duration of the opioid antagonist action, appropriate surveillance should be maintained. As with all potent opioids, profound analgesia is accompanied by respiratory depression and diminished sensitivity to CO2 stimulation which may persist into or recur in the postoperative period. Intraoperative hyperventilation may further alter postoperative response to CO2. Appropriate postoperative monitoring should be employed, particularly after infusions and large doses of Alfenta, to ensure that adequate spontaneous breathing is established and maintained in the absence of stimulation prior to discharging the patient from the recovery area.

Head Injuries

Alfenta should be used with caution in patients with head injury or increased intracranial pressure, due to the increased risk of respiratory depression. As with all opioids, Alfenta may obscure the clinical course of patients with head injuries and should be used only if clinically indicated.

Impaired Respiration

Alfenta should be used with caution in patients with pulmonary disease, decreased respiratory reserve or potentially compromised respiration. In such patients, opioids may additionally decrease respiratory drive and increase airway resistance. During anesthesia, this can be managed by assisted or controlled respiration.

Impaired Hepatic or Renal Function

In patients with liver or kidney dysfunction, Alfenta should be administered with caution due to the importance of these organs in the metabolism and excretion of Alfenta.

Drug Interactions

Both the magnitude and duration of central nervous system and cardiovascular effects may be enhanced when Alfenta is administered in combination with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics. Postoperative respiratory depression may be enhanced or prolonged by these agents. In such cases of combined treatment, the dose of one or both agents should be reduced. Limited clinical experience indicates that requirements for volatile inhalation anesthetics are reduced by 30 to 50% for the first sixty (60) minutes following Alfenta induction.

The concomitant use of erythromycin with Alfenta can significantly inhibit Alfenta clearance and may increase the risk of prolonged or delayed respiratory depression.

Cimetidine reduces the clearance of Alfenta. Therefore smaller Alfenta doses will be required with prolonged administration and the duration of action of Alfenta may be extended.

Perioperative administration of drugs affecting hepatic blood flow or enzyme function may reduce plasma clearance and prolong recovery.

Carcinogenesis, Mutagenesis and Impairment of Fertility

No long-term animal studies of Alfenta have been performed to evaluate carcinogenic potential. No structural chromosome mutations were produced in the in vivo micronucleus test in female rats at single intravenous doses of Alfenta as high as 20 mg/kg body weight (approximately 40 times the upper human dose), equivalent to a dose of 103 mg/m2 body surface area. No dominant lethal mutations were produced in the in vivo dominant lethal test in male and female mice at the maximum intravenous dose of 20 mg/kg (60 mg/m2). No mutagenic activity was revealed in the in vitro Ames Salmonella typhimurium test, with and without metabolic activation.

Pregnancy Category C

Alfenta has been shown to have an embryocidal effect in rats and rabbits when given in doses 2.5 times the upper human dose for a period of 10 days to over 30 days. These effects could have been due to maternal toxicity (decreased food consumption with increased mortality) following prolonged administration of the drug.

No evidence of teratogenic effects has been observed after administration of Alfenta in rats or rabbits.

There are no adequate and well-controlled studies in pregnant women. Alfenta should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

There are insufficient data to support the use of Alfenta in labor and delivery. Placental transfer of the drug has been reported; therefore, use in labor and delivery is not recommended.

Nursing Mothers

In one study of nine women undergoing postpartum tubal ligation, significant levels of Alfenta were detected in colostrum four hours after administration of 60 mcg/kg of Alfenta, with no detectable levels present after 28 hours. Caution should be exercised when Alfenta is administered to a nursing woman.

Pediatric Use

Adequate data to support the use of Alfenta in children under 12 years of age are not presently available.

Drug Abuse and Dependence

Alfenta (Alfentanil hydrochloride) is a Schedule II controlled drug substance that can produce drug dependence of the morphine type and therefore has the potential for being abused.

Opioid analgesics have been associated with abuse and dependence in health care providers and others with ready access to such drugs. Alfenta should be handled accordingly.

Overdosage

Overdosage would be manifested by extension of the pharmacological actions of Alfenta (Alfentanil hydrochloride) (see CLINICAL PHARMACOLOGY) as with other potent opioid analgesics. No experience of overdosage with Alfenta was reported during clinical trials. The intravenous LD50 of Alfenta is 43-51 mg/kg in rats, 72-74 mg/kg in mice, 72-82 mg/kg in guinea pigs and 60-88 mg/kg in dogs. Intravenous administration of an opioid antagonist such as naloxone should be employed as a specific antidote to manage respiratory depression.

The duration of respiratory depression following overdosage with Alfenta may be longer than the duration of action of the opioid antagonist. Administration of an opioid antagonist should not preclude immediate establishment of a patent airway, administration of oxygen, and assisted or controlled ventilation as indicated for hypoventilation or apnea. If respiratory depression is associated with muscular rigidity, a neuromuscular blocking agent may be required to facilitate assisted or controlled ventilation. Intravenous fluids and vasoactive agents may be required to manage hemodynamic instability.

How is Alfenta Supplied

Alfenta (Alfentanil hydrochloride) Injection for intravenous use. Each mL Contains: Active: Alfentanil base 500 mcg. Inactives: Sodium Chloride 9 mg and WFI Q.S Alfenta Injection is available as:

NDC 11098-060-02, 2 mL Ampule in packages of 10
NDC 11098-060-05, 5 mL Ampule in packages of 10
NDC 11098-060-10, 10 mL Ampule in packages of 5
NDC 11098-060-20, 20 mL Ampule in packages of 5

U.S. Patent No. 4,167,574
May 1995, November 1995

TAYLOR PHARMACEUTICALS
AN AKORN COMPANY

Decatur, IL 62522

AFA0N   Rev. 06/05

Alfenta 
Alfentanil hydrochloride injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:11098-060
Route of Administration INTRAVENOUS DEA Schedule CII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Alfentanil Hydrochloride (Alfentanil) Alfentanil 500 ug  in 1 mL
Inactive Ingredients
Ingredient Name Strength
sodium chloride 9 mg  in 1 mL
water  
Packaging
# Item Code Package Description
1 NDC:11098-060-02 10 AMPULE (10 AMPULE) in 1 PACKAGE
1 2 mL (2 MILLILITER) in 1 AMPULE
2 NDC:11098-060-05 10 AMPULE (10 AMPULE) in 1 PACKAGE
2 5 mL (5 MILLILITER) in 1 AMPULE
3 NDC:11098-060-10 5 AMPULE (5 AMPULE) in 1 PACKAGE
3 10 mL (10 MILLILITER) in 1 AMPULE
4 NDC:11098-060-20 5 AMPULE (5 AMPULE) in 1 PACKAGE
4 20 mL (20 MILLILITER) in 1 AMPULE
Labeler - TAYLOR PHARMACEUTICALS
Revised: 02/2008   TAYLOR PHARMACEUTICALS
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