Version May 2024
The FDA has issued a drug safety communication to announce safety-related updates to the prescribing information for immediate-release (IR) and extended-release (ER)/long-acting (LA) opioid analgesics, including updates to Boxed Warnings, Indications and Usage, Dosage and Administration, Warnings and Precautions, and the Medication Guide. These safety labeling changes are intended to provide clarity on appropriate patient populations for opioid treatment, appropriate dosage and administration, and updated information on the risks associated with opioid use. The required safety labeling changes include stating:
the risk of overdose increases as the dosage increases for all opioid pain medicines;
IR opioids should not be used for an extended period of time unless a patient's pain remains severe enough to require them and alternative treatment options continue to be inadequate;
many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine;
it is recommended to reserve ER/LA opioid pain medicines for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate; and
a warning about opioid-induced hyperalgesia (OIH), including information on differentiating OIH symptoms from those of opioid tolerance and withdrawal.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-prescribing-information-all-opioid-pain-medicines-provide-additional-guidance-safe-use.
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 guidance:
Safety: Doses should be titrated to appropriate effects based on patient factors and concomitant anesthetic agents; wide range of doses is dependent upon desired degree of analgesia/anesthesia.
Analgesia/A nesthesia: IV:
Weight-based dosing should utilize actual body weight for dosing calculations, unless >20% above ideal body weight, then use lean body weight for dosing calculations. Administer induction doses slowly over 3 minutes; as induction dosing may produce loss of vascular tone and hypotension, consider fluid replacement prior to induction. Refer to institutional protocols.
|
Indication |
Estimated duration of procedure |
Induction period (initial dose) |
Maintenance period (incremental injection) |
Maintenance period (continuous infusion) |
Total dose |
Comments |
|---|---|---|---|---|---|---|
|
a Gropper 2019; manufacturer's labeling. | ||||||
|
Analgesia (adjunctive agent) |
≤30 minutes |
8 to 20 mcg/kg |
3 to 5 mcg/kg every 5 to 20 minutes |
0.25 to 1 mcg/kg/minute |
8 to 40 mcg/kg |
Spontaneously breathing or assisted ventilation when required. |
|
Analgesia or anesthesia (adjunctive agent) |
30 to 60 minutes |
20 to 50 mcg/kg (~10 mcg/kg for laryngeal mask airway when co-administered with propofol) |
5 to 15 mcg/kg every 5 to 20 minutes |
Up to 75 mcg/kg |
May be administered in divided doses. Assisted or controlled ventilation required. Discontinue at least 30 minutes prior to end of surgery. | |
|
Anesthesia, induction (adjunctive agent) |
>45 minutes |
25 to 100 mcg/kg |
Up to 245 mcg/kg |
May be administered in divided doses. Assisted or controlled ventilation required. Concentration of volatile inhalation anesthetics reduced by 30% to 50% for initial hour. Following an anesthetic induction dose of alfentanil, alfentanil infusion rate requirements are reduced by 30% to 50% for the first hour of maintenance. | ||
|
Anesthesia, maintenance (adjunctive agent) |
>45 minutes |
0.5 to 2 mcg/kg/minute or general anesthetic |
Dependent on duration of procedure |
Assisted or controlled ventilation required. Discontinue at least 30 minutes prior to end of surgery. | ||
|
Monitored Anesthesia Care (MAC), analgesia |
3 to 8 mcg/kg |
3 to 5 mcg/kg every 5 to 20 minutes |
0.25 to 1 mcg/kg/minute |
3 to 40 mcg/kg |
Sedation, responsiveness, spontaneously breathing. May continue to the end of procedure. | |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution. The pharmacokinetics of alfentanil were evaluated in adult patients with chronic renal failure and compared to patients with normal renal function. Although Vdss was increased in patients with renal failure, elimination half-life was similar between the 2 groups (Ref). Therefore, prolongation of alfentanil duration of action is not expected and dosage adjustment is not necessary.
There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution and reduce the dose as needed; monitor closely.
In patients weighing >20% above ideal body weight, determine dose based on lean body weight.
Refer to adult dosing. Reduce the initial dose by up to 40%; consider the effect of the initial dose in determining supplemental doses.
(For additional information see "Alfentanil: Pediatric drug information")
Dosage guidance:
Safety: Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia. Alfentanil should only be used by clinicians trained in the provision of anesthesia to pediatric patients.
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 (Ref).
Procedural analgesia for lumbar puncture 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 (Ref).
Children ≥12 years and Adolescents: IV: See table; Note: Base dose on actual body weight unless >20% above ideal body weight, then base dose on lean body weight.
|
Indication |
Approximate Duration of Anesthesia (minutes) |
Induction Period (Initial Dose) (mcg/kg) |
Maintenance Period (Increments/ Infusion) |
Total Dose (mcg/kg) |
Effects |
|---|---|---|---|---|---|
|
Incremental IV injection |
≤30 minutes |
8 to 20 mcg/kg |
3 to 5 mcg/kg every 5 to 20 minutes or 0.5 to 1 mcg/kg/minute |
8 to 40 mcg/kg |
Spontaneously breathing or assisted ventilation when required. |
|
30 to 60 minutes |
20 to 50 mcg/kg |
5 to 15 mcg/kg every 5 to 20 minutes |
Up to 75 mcg/kg |
Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation. Discontinue at least 30 minutes prior to end of surgery. | |
|
Continuous IV infusion |
≥45 minutes |
50 to 75 mcg/kg |
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 minutes |
130 to 245 mcg/kg |
0.5 to 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 volatile inhalation anesthetics reduced by 30% to 50% for initial hour. Following an anesthetic induction dose of alfentanil, alfentanil IV infusion rate requirements are reduced by 30% to 50% for the first hour of maintenance. |
|
Monitored anesthesia care (MAC) |
3 to 8 mcg/kg |
3 to 5 mcg/kg every 5 to 20 minutes or 0.25 to 1 mcg/kg/minute |
3 to 40 mcg/kg |
Sedation, responsiveness, spontaneously breathing. May be continued to the end of the procedure. |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. The pharmacokinetics of alfentanil were evaluated in adult patients with chronic renal failure and compared to patients with normal renal function. Although Vdss was increased in patients with renal failure, elimination half-life was similar between the 2 groups (Ref). Therefore, prolongation of alfentanil duration of action is not expected and dosage adjustment is not necessary.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution and reduce the dose as needed; monitor closely.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Bradycardia (14%), chest wall rigidity (17%), hypertension (18%), tachycardia (12%)
Gastrointestinal: Nausea (28%), vomiting (18%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (1% to 3%), hypotension (10%)
Dermatologic: Pruritus (≤1%), urticaria (≤1%)
Local: Pain at injection site (≤1%)
Nervous system: Confusion (postoperative; ≤1%), dizziness (3% to 9%), drowsiness (≤3%), euphoria (postoperative; ≤1%), headache (≤1%), sedated state (≤3%; postoperative), shivering (≤1%)
Neuromuscular & skeletal: Laryngospasm (≤1%), muscle movements (3% to 9%; skeletal)
Ophthalmic: Blurred vision (1% to 3%)
Respiratory: Apnea (3% to 9%), hypercapnia (≤1%), respiratory depression (1% to 3%; postoperative)
<1%: Respiratory: Bronchospasm
Frequency not defined: Nervous system: Drug abuse, opioid dependence
Postmarketing:
Hypersensitivity: Anaphylaxis (Pepys 1994)
Nervous system: Agitation, allodynia (opioid-induced hyperalgesia) (FDA Safety Communication 2023), epileptiform seizure (Ross 2001), myoclonus
Neuromuscular & skeletal: Muscle rigidity (Benthuysen 1986)
Ophthalmic: Miosis (Black 1999)
Respiratory: Bradypnea, hypoxia
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
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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.
• Older adult: Use with caution in older adults; 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 30 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Generic: 1000 mcg/2 mL (2 mL [DSC]); 2500 mcg/5 mL (5 mL [DSC])
Yes
Solution (Alfentanil HCl Intravenous)
1000 mcg/2 mL (per mL): $5.26
2500 mcg/5 mL (per mL): $3.77
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
C-II
IV: Administer IV slowly over 3 minutes or by IV continuous infusion.
Parenteral: IV: Inject slowly over 3 to 5 minutes or by continuous IV infusion; in neonates, monitor closely for chest wall rigidity.
IV infusion: 10 mg in 250 mL (total volume) (concentration: 40 mcg/mL) of D5W or NS
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.
ALfentanil may be confused with Anafranil, fentaNYL, remifentanil, SUFentanil
Alfenta may be confused with Sufenta
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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: 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. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of ALfentanil. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of ALfentanil. Management: If use of alfentanil and strong CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: 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. Risk D: Consider therapy modification
Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Opioid Agonists may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. 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. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nalfurafine: Opioid Agonists may enhance the adverse/toxic effect of Nalfurafine. Opioid Agonists may diminish the therapeutic effect of Nalfurafine. Risk C: Monitor therapy
Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: 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. Risk X: Avoid combination
Nefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: 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. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. 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 tonic clonic seizures. Risk C: Monitor therapy
Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination
Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) 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. Risk C: 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. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: 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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility (Brennan 2013).
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).
Alfentanil is present in breast milk (Giesecke 1985).
Breast milk was sampled in nine nonbreastfeeding women undergoing tubal ligation. Alfentanil 50 mcg/kg IV was administered following intubation and additional doses given as needed during the procedure. Alfentanil was present in breast milk 4 hours after the surgery and no longer present in breast milk 28 hours after surgery (Giesecke 1985).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; monitor infants for excess sedation and respiratory depression. The Academy of Breast Feeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).
Respiratory and cardiovascular status, blood pressure, heart rate; continue to monitor well after surgery because of the risk for delayed effects
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
Note: An early study of continuous infusion suggested nonlinear pharmacokinetics in neonates (Wiest 1991).
Onset of action: Rapid, within 5 minutes
Duration (dose dependent): 30 to 60 minutes
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
Protein binding:
Neonates: 67%
Adults: 88% to 92%
Bound to alpha1-acid glycoprotein
Metabolism: Hepatic
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
Excretion: Only 1% of dose is excreted unchanged; urine (major route of elimination of metabolites)
Hepatic function impairment: Reduced plasma clearance and extended terminal elimination may develop.
Older adult: Reduced plasma clearance and extended terminal elimination may develop.
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