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Alfentanil


Pronunciation

 (al FEN ta nil)


U.S. Brand Names

 Alfenta®


Synonyms

 Alfentanil Hydrochloride


Generic Available

 Yes


Canadian Brand Names

 Alfenta®


Use

 Analgesic adjunct given by continuous infusion or in incremental doses in maintenance of anesthesia with barbiturate or N2O or a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required


Restrictions

 C-II


Pregnancy Risk Factor

 C


Contraindications

 Hypersensitivity to alfentanil hydrochloride, to narcotics, or any component of the formulation; increased intracranial pressure, severe respiratory depression


Warnings/Precautions

 Use with caution in patients with drug dependence, head injury, acute asthma and respiratory conditions; hypotension has occurred in neonates with respiratory distress syndrome; use caution when administering to patients with bradyarrhythmias; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; inject slowly over 3-5 minutes. Alfentanil may produce more hypotension compared to fentanyl, therefore, be sure to administer slowly and ensure patient has adequate hydration.


Adverse Reactions

>10%:

Cardiovascular: Bradycardia, peripheral vasodilation

Central nervous system: Drowsiness, sedation, increased intracranial pressure

Gastrointestinal: Nausea, vomiting, constipation

Endocrine & metabolic: Antidiuretic hormone release

Ocular: Miosis

1% to 10%:

Cardiovascular: Cardiac arrhythmia, orthostatic hypotension

Central nervous system: Confusion, CNS depression

Ocular: Blurred vision

<1%: Convulsions, mental depression, paradoxical CNS excitation or delirium, dizziness, dysesthesia, rash, urticaria, itching, biliary tract spasm, urinary tract spasm, respiratory depression, bronchospasm, laryngospasm, physical and psychological dependence with prolonged use; cold, clammy skin


Overdosage/Toxicology

 Symptoms of overdose include miosis, respiratory depression, seizures, and CNS depression. Naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg; may precipitate withdrawal.


Drug Interactions

 Substrate of CYP3A4 (major)

Increased effect: Dextroamphetamine may enhance the analgesic effect of morphine and other opiate agonists

Increased toxicity: CNS depressants (eg, benzodiazepines, barbiturates, tricyclic antidepressants), erythromycin, reserpine, beta-blockers

CYP3A4 inhibitors: May increase the levels/effects of alfentanil. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.


Stability

 Dilute in D5W, NS, or LR


Compatibility

 Stable in D5W, NS, D5LR, D5NS

Y-site administration: Compatible: Cisatracurium, etomidate, gatifloxacin, linezolid, propofol, remifentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, thiopental

Compatibility in syringe: Compatible: Atracurium, midazolam, ondansetron


Mechanism of Action

 Binds with stereospecific receptors at many sites within the CNS, increases pain threshold, alters pain perception, inhibits ascending pain pathways; is an ultra short-acting narcotic


Pharmacodynamics/Kinetics

Onset of action: Rapid

Duration (dose dependent): 30-60 minutes

Distribution: Vd: Newborns, premature: 1 L/kg; Children: 0.163-0.48 L/kg; Adults: 0.46 L/kg

Half-life elimination: Newborns, premature: 5.33-8.75 hours; Children: 40-60 minutes; Adults: 83-97 minutes


Dosage

 Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia

Children <12 years: Dose not established

Adults: Dose should be based on ideal body weight as follows (see table):


Administration

Alfentanil

Indication Approx Duration of Anesthesia
(min)		 Induction Period (Initial Dose)
(mcg/kg)		 Maintenance Period (Increments/ Infusion) Total Dose
(mcg/kg)		 Effects
Incremental injection 30 8-20 3-5 mcg/kg or 0.5-1 mcg/kg/min 8-40 Spontaneously breathing or assisted ventilation when required.
30-60 20-50 5-15 mcg/kg Up to 75 Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.
Continuous infusion >45 50-75 0.5-3 mcg/kg/min average infusion rate 1-1.5 mcg/kg/min Dependent on duration of procedure Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.
Anesthetic induction >45 130-245 0.5-1.5 mcg/kg/min or general anesthetic Dependent on duration of procedure Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.

Administration

 Administer I.V. slowly over 3-5 minutes or by I.V. continuous infusion.


Monitoring Parameters

 Respiratory rate, blood pressure, heart rate


Reference Range

 100-340 ng/mL (depending upon procedure)


Additional Information

 Alfentanil may produce more muscle rigidity compared to fentanyl, therefore, be sure to administer slowly.


Anesthesia and Critical Care Concerns/Other Considerations

 Alfentanil may produce more muscle rigidity compared to fentanyl, therefore, be sure to administer slowly.


Dental Health: Effects on Dental Treatment

 Key adverse event(s) related to dental treatment: Orthostatic hypotension.

Erythromycin inhibits the liver metabolism of alfentanil resulting in increased sedation and prolonged respiratory depression.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 Sedation is common, may see depression or confusion, rarely may cause seizures or delirium


Mental Health: Effects on Psychiatric Treatment

 CNS depressant and beta-blockers may increase toxicity; phenothiazines may antagonize analgesic effect


Dosage Forms

 Injection, solution, as hydrochloride [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)


References

Bartkowski RR and McDonnell TE, "Prolonged Alfentanil Effect Following Erythromycin Administration," Anesthesiology , 1990, 73(3):566-8.

Bartkowski RR, Goldberg ME, Larijani GE, et al, "Inhibition of Alfentanil Metabolism by Erythromycin," Clin Pharmacol Ther , 1989, 46(1):99-102.

Bodenham A and Park GR, "Alfentanil Infusions in Patients Requiring Intensive Care," Clin Pharmacokinet , 1988, 15(4):216-26.

Davis PJ, Killian A, Stiller RL, et al, "Pharmacokinetics of Alfentanil in Newborn Premature Infants and Older Children," Dev Pharmacol Ther , 1989, 13(1):21-7.

Kirkham SR and Pugh R, "Opioid Analgesia in Uraemic Patients," Lancet , 1995, 345(8958):1185.

Marlow N, Weindling AM, Van Peer A, et al, "Alfentanil Pharmacokinetics in Preterm Infants," Arch Dis Child , 1990, 65(4 Spec No):349-51.

Meistelman C, Saint-Maurice C, Lepaul M, et al, "A Comparison of Alfentanil Pharmacokinetics in Children and Adults," Anesthesiology , 1987, 66(1):13-6.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings," Chest , 2003, 123(3):897-922.

Pokela ML, Ryhanen PT, Koivisto ME, et al, "Alfentanil-Induced Rigidity in Newborn Infants," Anesth Analg , 1992, 75(2):252-7.

Scholz J, Steinfath M, and Schulz M, "Clinical Pharmacokinetics of Alfentanil, Fentanyl, and Sufentanil. An Update," Clin Pharmacokinet , 1996, 31(4):275-92.


International Brand Names

 Alfenta® (CA); Rapifen® (HK, LU, NZ, YU)


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