Alfentanil

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Alfentanil may be confused with Anafranil®, fentanyl, remifentanil, sufentanil
Alfenta® may be confused with Sufenta®

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Alfenta®

PHARMACOLOGIC CATEGORY
Analgesic, Opioid
Anilidopiperidine Opioid

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

Anesthesia: I.V.: Dose should be based on ideal body weight as follows (see table).

Adult Dosage Adjustments

Incremental injection in anesthesia ≤ 30 minutes: Initial dose (induction period): 8-20 mcg/kg Maintenance period (increments/infusion): 3-5 mcg/kg or 0.5-1 mcg/kg/minute Total dose: 8-40 mcg/kg Appropriate effects: Spontaneously breathing or assisted ventilation when required

Incremental injection in anesthesia of 30-60 minutes: Initial dose (induction period): 20-50 mcg/kg Maintenance period (increments/infusion): 5-15 mcg/kg Total dose: Up to 75 mcg/kg Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.

Continuous infusion >45 minutes: Initial dose (induction period): 50-75 mcg/kg Maintenance period (increments/infusion): 0.5-3mcg/kg/minute; average infusion rate: 1-1.5 mcg/kg/minute Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.

Anesthetic induction >45 minutes: Initial dose (induction period): 130-245 mcg/kg Maintenance period (increments/infusion): 0.5-1.5 mcg/kg/minute or general anesthetic Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.

DOSING: PEDIATRIC

(For additional information see "Alfentanil: Pediatric drug information")
Children <12 years: Dose has not been established.

Children ≥ 12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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

DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL)
Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)

GENERIC EQUIVALENT AVAILABLE — Yes

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

COMPATIBILITY — Stable in D5W, NS, LR, 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.

USE — Analgesic adjunct for the induction and maintenance of general anesthesia; analgesic component for monitored anesthesia care (MAC)

ADVERSE REACTIONS SIGNIFICANT
>10%:
Cardiovascular: Bradycardia, peripheral vasodilation
Central nervous system: Drowsiness, sedation, intracranial pressure increased
Endocrine & metabolic: Antidiuretic hormone release
Gastrointestinal: Nausea, vomiting, constipation
Ocular: Miosis

1% to 10%:
Cardiovascular: Cardiac arrhythmia, orthostatic hypotension
Central nervous system: Confusion, CNS depression
Ocular: Blurred vision

<1% (Limited to important or life-threatening): 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

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

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Opioid agonist toxicities: Shares the toxic potentials of opiate agonists, and precautions of opiate agonist therapy should be observed.

Disease-related concerns: Bradyarrhythmias: Use with caution when administering to patients with bradyarrhythmias. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Obesity: Use with caution in patients who are morbidly obese. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function.

Special populations: Neonates: Hypotension has occurred in neonates with respiratory distress syndrome. Pediatrics: Safety and efficacy have not been established in children <12 years old.

Other warnings/precautions: Rapid infusion: Inject slowly over 3-5 minutes; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Trained individuals: Due to the high incidence of apnea, hypotension, tachycardia and muscle rigidity; it should be administered by individuals specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.

RESTRICTIONS — C-II

METABOLISM / TRANSPORT EFFECTS — Substrate of CYP3A4 (major)

DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification

Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy

Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Alfentanil. Risk D: Consider therapy modification

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy

Beta-Blockers: Anilidopiperidine Opioids may enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Anilidopiperidine Opioids may enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy

Cimetidine: May decrease the metabolism of Alfentanil. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Diltiazem: May increase the serum concentration of Alfentanil. Risk C: Monitor therapy

Fluconazole: May decrease the metabolism of Alfentanil. Risk D: Consider therapy modification

Fospropofol: Alfentanil may enhance the adverse/toxic effect of Fospropofol. Specifically, the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or grand mal seizures. Risk C: Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Alfentanil. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk D: Consider therapy modification

MAO Inhibitors: Anilidopiperidine Opioids may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Management: Avoid use of fentanyl (and other anilidopiperidine opioids when possible) in patients who have used a monoamine oxidase inhibitor within the past 14 days due to reports of unpredictable but severe adverse effects. Risk X: Avoid combination

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy

Propofol: Alfentanil may enhance the adverse/toxic effect of Propofol. Specifically the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or grand mal seizures. Risk C: Monitor therapy

Rifamycin Derivatives: May increase the metabolism of Alfentanil. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy

Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy

Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — C (show table)

MONITORING PARAMETERS — Respiratory rate, blood pressure, heart rate

REFERENCE RANGE — 100-340 ng/mL (depending upon procedure)

CANADIAN BRAND NAMES — Alfentanil Injection, USP; Alfenta®

INTERNATIONAL BRAND NAMES — Alfast (BR); Brevafen (AR); Fanaxal (ES); Fentalim (IT); Rapifen (AE, AT, AU, BE, BG, BH, BR, CH, CN, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HN, HR, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LU, LY, NL, NO, OM, PL, PT, PY, QA, RU, SA, SE, SG, SY, TR, TW, UY, VE, YE, ZA)

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