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Alfentanil

Generic name: alfentanil systemic

Brand names: Alfenta

Boxed Warning

Addiction, abuse, and misuse

Alfentanil 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 alfentanil, and monitor all patients regularly for the development of these behaviors and conditions.

Dosage Forms

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

Solution, Intravenous [preservative free]:

Generic: 1000 mcg/2 mL (2 mL); 2500 mcg/5 mL (5 mL)

Pharmacology

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 opioid

Pharmacokinetics/Pharmacodynamics

Distribution

Vd:

Newborns (premature): 0.5 to 0.6 L/kg (Davis 1988; Marlow 1990)

Children: 0.163 to 0.4 L/kg (Davis 1989; Meistelman 1987)

Adults: 0.4 to 1 L/kg

Metabolism

Hepatic

Excretion

Only 1% of dose is excreted unchanged; urine (major route of elimination of metabolites)

Onset of Action

Rapid, within 5 minutes

Duration of Action

Dose dependent: 30 to 60 minutes

Half-Life Elimination

Newborns (premature): 5.33 to 9 hours (Davis 1988; Marlow 1990)

Children: 40 to 63 minutes (Davis 1988; Meistelman 1987; Roure 1987)

Adults: 90 to 111 minutes

Protein Binding

Neonates: 67%; Adults: 88% to 92%; bound to alpha1-acid glycoprotein

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Reduced plasma clearance and extended terminal elimination may develop.

Special Populations: Elderly

Reduced plasma clearance and extended terminal elimination may develop.

Use: Labeled Indications

Analgesia: Analgesic adjunct for the maintenance of anesthesia with barbiturate/nitrous oxide/oxygen; analgesic with nitrous oxide/oxygen in the maintenance of general anesthesia; analgesic component for monitored anesthesia care.

Anesthetic: Primary anesthetic for induction of anesthesia in general surgery when endotracheal intubation and mechanical ventilation are required.

Contraindications

Hypersensitivity (eg, anaphylaxis) to alfentanil or any component of the formulation.

Canadian labeling: Additional contraindication (not in US labeling): Suspected surgical abdomen (eg, acute appendicitis or pancreatitis); mild pain that can be managed with other pain medications; acute or severe bronchial asthma, chronic obstructive airway, status asthmaticus; acute respiratory depression, hypercapnia, cor pulmonale; acute alcoholism, delirium tremens, and convulsive disorders; severe CNS depression, increased cerebrospinal or intracranial pressure and head injury; concurrent use or use within 14 days of an MAO inhibitor; women who are nursing, pregnant, or during labor and delivery

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity can not be ruled out with certainty.

Dosage and Administration

Dosing: Adult

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

Anesthesia: Base dose on actual body weight unless >20% above ideal body weight, then base dose on lean body weight. Administer induction doses slowly over 3 minutes; as induction dosing may produce loss of vascular tone and hypotension, consider fluid replacement prior to induction.

Alfentanil Dosage Range for Use During Anesthesia

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 to 20

3 to 5 mcg/kg every 5 to 20 minutes or 0.5 to 1 mcg/kg/minute

8 to 40

Spontaneously breathing or assisted ventilation when required.

30 to 60

20 to 50

5 to 15 mcg/kg every 5 to 20 minutes

Up to 75

Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.

Continuous infusion

>45

50 to 75

0.5 to 3 mcg/kg/minute; average infusion rate 1 to 1.5 mcg/kg/minute

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 to 245

0.5 to 1.5 mcg/kg/minute or general anesthetic

Dependent on duration of procedure

Assisted or controlled ventilation required. Concentration of volatile inhalation anesthetics reduced by 30% to 50% for initial hour.

Monitored Anesthesia Care (MAC)

3 to 8

3 to 5 mcg/kg every 5 to 20 minutes or 0.25 to 1 mcg/kg/minute

3 to 40

Sedation, responsiveness, spontaneously breathing

Table has been converted to the following text.

Alfentanil Dosage Range for Use During Anesthesia

Incremental injection in anesthesia ≤30 minutes:

  • Initial dose (induction period): 8 to 20 mcg/kg
  • Maintenance period (increments/infusion): 3 to 5 mcg/kg every 5 to 20 minutes or 0.5 to 1 mcg/kg/minute
  • Total dose: 8 to 40 mcg/kg
  • Appropriate effects: Spontaneously breathing or assisted ventilation when required

Incremental injection in anesthesia of 30 to 60 minutes:

  • Initial dose (induction period): 20 to 50 mcg/kg
  • Maintenance period (increments/infusion): 5 to 15 mcg/kg every 5 to 20 minutes
  • 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 to 75 mcg/kg
  • Maintenance period (increments/infusion): 0.5 to 3mcg/kg/min; average infusion rate: 1 to 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 to 245 mcg/kg
  • Maintenance period (increments/infusion): 0.5 to 1.5 mcg/kg/minute or general anesthetic
  • Total dose: Dependent on duration of procedure
  • Appropriate effects: Assisted or controlled ventilation required. Concentration of volatile inhalation anesthetics reduced by 30% to 50% for initial hour.

Monitored Anesthesia Care (MAC):

  • Initial dose (induction period): 3 to 8 mcg/kg
  • Maintenance period (increments/infusion): 3 to 5 mcg/kg every 5 to 20 minutes or 0.25 to 1 mcg/kg/minute
  • Total dose: 3 to 40 mcg/kg
  • Appropriate effects: Sedation, responsiveness, spontaneously breathing

Dosing: Geriatric

Refer to adult dosing. Reduce the initial dose by up to 40%; consider the effect of the initial dose in determining supplemental doses.

Dosing: Pediatric

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

Anesthesia:

Children <12 years:

Pre-induction, emergence agitation prevention, analgesia in tonsillectomy, or dental procedure patients undergoing general anesthesia: Limited data available: IV: 10 to 20 mcg/kg/dose (Annila 1999; Bartolek 2007; Kim 2009; Kwak 2010; Ng 1999; Rahman Al-Refai 2007)

Procedural analgesia for LP or bone marrow aspiration (in addition to propofol): Limited data available: Intermittent IV: 2 to 3 mcg/kg/dose (total dose: mean: 1.4 mcg/kg ± 2.4; range: 1.8 to 9.6 mcg/kg) administered to 20 patients ages 2 to 16 years old (von Heijne 2004)

Children ≥12 years and Adolescents: See table; Note: Base dose on actual body weight unless >20% above ideal body weight, then base dose on lean body weight

Alfentanil Dosing

Indication

Approximate Duration of Anesthesia (minute)

Induction Period (Initial Dose) (mcg/kg)

Maintenance Period (Increments/ Infusion)

Total Dose (mcg/kg)

Effects

Incremental injection

≤30

8-20

3-5 mcg/kg every 5-20 minutes or

0.5-1 mcg/kg/minute

8-40

Spontaneously breathing or assisted ventilation when required.

30-60

20-50

5-15 mcg/kg every 5-20 minutes

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/minute;

average infusion rate: 1-1.5 mcg/kg/minute

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/minute

or general anesthetic

Dependent on duration of procedure

Assisted or controlled ventilation required. Administer induction dose slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.

Monitored Anesthesia Care (MAC)

3-8

3-5 mcg/kg every 5-20 minutes or 0.25-1 mcg/kg/minute

3-40

Sedation, responsiveness, spontaneously breathing.

Table has been converted to the following text.

Alfentanil Dosing (By Indication):

For incremental injection in anesthesia of ≤30 minutes:

Initial dose (induction period): 8-20 mcg/kg

Maintenance period dose: 3-5 mcg/kg every 5-20 minutes or 0.5-1 mcg/kg/minute

Total dose: 8-40 mcg/kg

Appropriate effects: Spontaneously breathing or assisted ventilation when required

For incremental injection in anesthesia of 30-60 minutes:

Initial dose (induction period): 20-50 mcg/kg

Maintenance period dose: 5-15 mcg/kg every 5-20 minutes

Total dose: Up to 75 mcg/kg

Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.

For continuous infusion >45 minutes:

The initial dose (induction period): 50-75 mcg/kg

Maintenance period dose: 0.5-3 mcg/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

For anesthetic induction >45 minutes:

The initial dose (induction period): 130-245 mcg/kg

Maintenance period dose: 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 induction dose slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.

For Monitored Anesthesia Care (MAC):

The initial dose (induction period): 3-8 mcg/kg

Maintenance period dose: 3-5 mcg/kg every 5 – 20 minutes or 0.25-1 mcg/kg/minute

Total dose: 30-40 mcg/kg

Appropriate effects: Sedation, responsiveness, spontaneously breathing.

Dosing: Obesity

In patients weighing >20% above ideal body weight, determine dose based on lean body weight.

Reconstitution

May dilute in NS, D5W, D5NS, or LR to a concentration of 25 to 80 mcg/mL.

Administration

IV: Administer IV slowly over 3 minutes or by IV continuous infusion.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light.

Drug Interactions

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Alvimopan: Opioid Agonists 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. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Opioid Agonists. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

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

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetidine: May increase the serum concentration of Alfentanil. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Crizotinib: May increase the serum concentration of Alfentanil. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification

Desmopressin: Opioid Agonists may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

DiazePAM: May enhance the CNS depressant effect of Alfentanil. Hypotension may also occur. Monitor therapy

DilTIAZem: May increase the serum concentration of Alfentanil. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Avoid combination

Enzalutamide: May decrease the serum concentration of Alfentanil. Avoid combination

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erythromycin (Systemic): May increase the serum concentration of Alfentanil. Management: For patients who are actively receiving erythromycin, caution should be used in administering alfentanil; monitor for increased anesthetic and respiratory depressant effects. Consider using lower doses of alfentanil or an alternative anesthetic. Consider therapy modification

Fluconazole: May increase the serum concentration of Alfentanil. Management: Monitor for increased anesthetic and respiratory depressant effects if alfentanil is combined with fluconazole. Consider using lower initial doses of alfentanil or an alternative anesthetic. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. If combined, larger doses of opioid agonists will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Alfentanil. Management: Monitor for increased anesthetic and respiratory depressant effects of alfentanil if these agents are combined. Consider using lower initial doses of alfentanil or an alternative anesthetic. Canadian labeling recommends avoidance of this combination. Consider therapy modification

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. 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 tonic clonic seizures. Monitor therapy

Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Alfentanil. Management: Monitor closely for decreased alfentanil effectiveness. Increased alfentanil doses will likely be needed. Alternatively, changing from alfentanil to a different opioid anesthetic (e.g., sufentanil) may also be considered. Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonergic Agents (High Risk): Opioid Agonists may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Cardiovascular: Hypertension (18%), chest wall rigidity (17%), bradycardia (14%), tachycardia (12%)

Gastrointestinal: Nausea (28%), vomiting (18%)

1% to 10%:

Cardiovascular: Hypotension (10%), cardiac arrhythmia (1% to 3%)

Central nervous system: Dizziness (3% to 9%), drowsiness (≤3%), sedation (≤3%; postoperative)

Neuromuscular & skeletal: Muscle movements (3% to 9%; skeletal)

Ophthalmic: Blurred vision (1% to 3%)

Respiratory: Apnea (3% to 9%), respiratory depression (1% to 3%; postoperative)

Frequency not defined:

Cardiovascular: Peripheral vasodilation

Gastrointestinal: Constipation

Ophthalmic: Miosis

<1%, postmarketing, and/or case reports: Anaphylaxis, bronchospasm, confusion (postoperative), drug dependence, euphoria (postoperative), headache, hypercapnia, laryngospasm, muscle rigidity (neck and extremities), myoclonus, pruritus, shivering, urticaria

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). Monitor for symptoms of hypotension following initiation or dose titration.
  • Hypersensitivity: Anaphylaxis reactions may occur.
  • Respiratory depression: Serious, life-threatening, or fatal respiratory depression, even when used as recommended, may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
  • Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of alfentanil and serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs, 5-HT3 receptor antagonists, mirtazapine, trazodone, tramadol) and agents that impair metabolism of serotonin (eg, MAO inhibitors). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue alfentanil if serotonin syndrome is suspected.
  • Opioid agonist toxicities: Shares the toxic potentials of opioid agonists, and precautions of opioid agonist therapy should be observed.

Disease-related concerns:

  • Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
  • Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.
  • Bradyarrhythmias: Bradycardia may occur; use with caution when administering to patients with bradyarrhythmias. Degree of bradycardia may be more pronounced when administered with non-vagolytic skeletal muscle relaxants (eg, vecuronium, cisatracurium) or when anticholinergic agents (eg, atropine) are not used.
  • Delirium tremens: Use with caution in patients with delirium tremens.
  • Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
  • Hepatic impairment: Use with caution in patients with hepatic impairment; reduce the dose as needed; monitor closely.
  • Obesity: Use with caution in patients who are morbidly obese. Reduce dose; use lean body weight for dosing in patients >20% over ideal body weight.
  • Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
  • Psychosis: Use with caution in patients with toxic psychosis.
  • Renal impairment: Use with caution in patients with renal impairment.
  • Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages.
  • Seizures: Use with caution in patients with a history of seizure disorders; may increase risk or exacerbate preexisting seizure disorders.
  • Skeletal muscle rigidity: May produce muscular rigidity that involves all skeletal muscles, including those of the neck and extremities; incidence is dose-related. Initial doses up to 20 mcg/kg may cause skeletal muscle rigidity, particularly of the truncal muscles. Doses >130 mcg/kg will consistently cause muscle rigidity with an immediate onset. Consider the concomitant use of a nondepolarizing skeletal muscle relaxant to decrease the incidence.
  • Sleep-related disorders: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea, hypoxemia) in a dose-dependent fashion; use with caution.
  • Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

  • Benzodiazepines or other CNS depressants: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in hypotension, profound sedation, respiratory depression, coma, and death. Following the administration of alfentanil, the dose of other CNS depressant drugs should be reduced.
  • CYP3A4 interactions: Use with all CYP3A4 inhibitors may result in an increase in alfentanil plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP3A4 inducer may result in increased alfentanil concentrations. Monitor patients receiving alfentanil and any CYP3A4 inhibitor or inducer.
  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

  • Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Appropriately reduce the initial dose; consider the effect of the initial dose in determining supplemental doses.
  • Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Appropriately reduce the initial dose; consider the effect of the initial dose in determining supplemental doses. Plasma clearance of alfentanil may be reduced and postoperative recovery may be prolonged.

Other warnings/precautions:

  • Abuse/misuse/diversion: [US Boxed Warning]: Alfentanil exposes 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 alfentanil and monitor all patients regularly for the development of these behaviors and conditions.
  • Discontinuation of therapy: Discontinue infusion at least 10 to 15 minutes prior to the end of surgery during general anesthesia; during administration for Monitored Anesthesia Care (MAC), infusions may be continued to the end of the procedure.
  • Trained individuals: Alfentanil should be administered health care providers specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; opioid antagonist, resuscitative and intubation equipment should be readily available.

Monitoring Parameters

Respiratory and cardiovascular status, blood pressure, heart rate; continue to monitor well after surgery because of the risk for delayed effects

Pregnancy

Pregnancy Considerations

Alfentanil crosses the placenta (Cartwright 1989; Gepts 1986).

Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Opioids may cause respiratory depression and psychophysiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.

The pharmacokinetic properties of alfentanil are not influenced by pregnancy when administered prior to delivery (Gepts 1986). Alfentanil has been evaluated for use in obstetrical analgesia (Mattingly 2003); other agents are more commonly used (ACOG 209 2019).

The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).

Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility in men and women (Brennan 2013).

Patient Education

What is this drug used for?

  • It is used to put you to sleep for surgery.
  • It is used to ease pain.

Frequently reported side effects of this drug

  • Vomiting
  • Stiff muscles
  • Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Severe headache
  • Severe dizziness
  • Passing out
  • Vision changes
  • Slow heartbeat
  • Fast heartbeat
  • Seizures
  • Noisy breathing
  • Chest pain
  • Abnormal movements
  • Trouble breathing
  • Slow breathing
  • Shallow breathing
  • Confusion
  • Severe fatigue
  • Sexual dysfunction (males)
  • No menstrual periods
  • Decreased sex drive
  • Trouble getting pregnant
  • Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss
  • Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated January 15, 2020.