SUFentanil

Dosage Forms

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

Solution, Intravenous [preservative free]:

Generic: 50 mcg/mL (1 mL); 100 mcg/2 mL (2 mL); 250 mcg/5 mL (5 mL)

Tablet Sublingual, Sublingual, as citrate:

Dsuvia: 30 mcg [contains fd&c blue #2 (indigotine)]

Pharmacology

Mechanism of Action

Binds to opioid receptors throughout the CNS. Once receptor binding occurs, effects are exerted by opening K+ channels and inhibiting Ca++ channels. These mechanisms increase pain threshold, alter pain perception, inhibit ascending pain pathways; short-acting opioid; dose-related inhibition of catecholamine release (up to 30 mcg/kg) controls sympathetic response to surgical stress.

Pharmacokinetics/Pharmacodynamics

Distribution

V_dss: Children 2 to 8 years: 2.9 ± 0.6 L/kg; Adults: 1.7 ± 0.2 L/kg

Metabolism

Primarily hepatic and small intestine via demethylation and dealkylation

Excretion

Urine (2% excreted as unchanged drug; 80% metabolites) within 24 hours

Clearance:

Children 2 to 8 years: 30.5 ± 8.8 mL/minute/kg

Adolescents: 12.8 ± 12 mL/minute/kg

Adults: 12.7 ± 0.8 mL/minute/kg

Onset of Action

Analgesia: IV: 1 to 3 minutes; Epidural: 10 minutes; Sublingual tablets: ~30 minutes (Fisher 2018)

Time to Peak

Sublingual tablet: 1 hour

Duration of Action

Dose dependent: Anesthesia adjunct doses: IV: 5 minutes; Epidural: 10 to 15 mcg with bupivacaine 0.125%: 1.7 hours; Sublingual tablets: ~3 hours (Fisher 2018)

Half-Life Elimination

IV: Neonates: 7.2 ± 2.7 hours; Infants and Children (2 to 8 years): 97 ± 42 minutes; Adolescents 10 to 15 years: 76 ± 33 minutes; Adults: 164 minutes

Sublingual tablet: 2.5 ± 0.85 hours (Fisher 2018)

Protein Binding

Neonates: 79%; Adults: 91% to 93%; primarily to alpha 1-acid glycoprotein

Use: Labeled Indications

Acute pain management (sublingual tablet): Management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

Limitations of use: Reserve for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Administer by health care provider in a health care setting (eg, hospital, surgical center, emergency department) only; not for home use. Do not administer >72 hours (has not been studied).

Epidural analgesia (injection): For epidural administration as an analgesic combined with low-dose bupivacaine during labor and vaginal delivery.

Surgical analgesia (injection): Analgesic adjunct for the maintenance of balanced general anesthesia in patients who are intubated and ventilated.

Surgical anesthesia (injection): As a primary anesthetic agent for the induction and maintenance of anesthesia with 100% oxygen in patients undergoing major surgical procedures; in patients who are intubated and ventilated, such as cardiovascular surgery or neurosurgical procedures in the sitting position; to provide favorable myocardial and cerebral oxygen balance or when extended postoperative ventilation is anticipated.

Contraindications

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

Additional contraindications for sublingual tablets: Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to fentanyl or other morphinomimetics; IV use during labor or before clamping cord during cesarean section; epidural administration in patients with severe hemorrhage or shock, septicemia, or infection at proposed puncture site

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 cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Acute pain management: Sublingual tablet: Initial: Sublingual: 30 mcg; may repeat as needed with a minimum of 1 hour between doses; maximum dose: 360 mcg/day (12 tablets); do not use for >72 hours

Note: Only administer in a certified medically supervised health care setting by a health care provider; discontinue treatment prior to discharge from supervised setting.

Surgical analgesia (as a component of balanced anesthesia) (surgery expected to last: 1 to 2 hours): IV: Total dose: 1 to 2 mcg/kg with N₂O/O₂; ≥75% of total dose may be administered by slow injection or infusion prior to intubation (titrate to individual response)

Maintenance:

Incremental dosing: According to the manufacturer, 10 to 25 mcg may be administered as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. May also administer doses in the range of 5 to 20 mcg as needed (Barash 2009) or 0.1 to 0.25 mcg/kg as needed (Miller 2010). Total dose should not exceed 1 mcg/kg/hour of expected surgical time.

Continuous infusion: May also be administered as a continuous infusion with the infusion rate based on the induction dose used. Maximum infusion rate according to the manufacturer: 1 mcg/kg/hour. May also administer doses in the range of 0.3 to 0.9 mcg/kg/hour (Barash 2009) or 0.5 to 1.5 mcg/kg/hour (Miller 2010).

Surgical analgesia (as a component of balanced anesthesia) (surgery expected to last 2 to 8 hours): Total dose: 2 to 8 mcg/kg with N₂O/O₂; ≤75% of total dose may be administered by slow injection or infusion prior to intubation (titrate to individual response).

Maintenance:

Incremental dosing: According to the manufacturer, 10 to 50 mcg may be administered as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Total dose should not exceed 1 mcg/kg/hour of expected surgical time.

Continuous infusion: May also be administered as a continuous infusion with the infusion rate based on the induction dose used. Maximum infusion rate according to the manufacturer: 1 mcg/kg/hour. May also administer doses in the range of 0.3 to 0.9 mcg/kg/hour (Barash, 2009) or 0.5 to 1.5 mcg/kg/hour (Miller, 2010).

Surgical anesthesia: Total dose: 8 to 30 mcg/kg as a slow injection, infusion, or injection followed by infusion; titrate to individual patient response. Note: In patients administered high doses of sufentanil, qualified personnel and adequate facilities are necessary to manage the potential for postoperative respiratory depression.

Maintenance:

Incremental dosing: 0.5 to 10 mcg/kg as needed in anticipation of surgical stress

Continuous infusion: Base infusion rate on the induction dose so that the total dose for the procedure does not exceed 30 mcg/kg

Analgesia for labor and delivery: Epidural: 10 to 15 mcg with bupivacaine 0.125% with/without epinephrine. Dose can be repeated twice (for a total of 3 doses) at not less than 1-hour intervals until delivery.

Dosing: Geriatric

Refer to adult dosing. Use with caution and titrate slowly; monitor closely for signs of CNS and respiratory depression.

Dosing: Pediatric

Note: Doses should be titrated to appropriate effects; wide range of doses, dependent upon patient age (particularly young infants), desired degree of analgesia or anesthesia; use lean body weight to dose patients who are >20% above ideal body weight. Should only be administered under the supervision of a qualified physician experienced in the use of anesthetics.

Cardiac surgery anesthesia: Infants, Children, and Adolescents: IV: Initial: 5 to 25 mcg/kg; repeat maintenance doses: 1 to 5 mcg/kg/doses up to 25 to 50 mcg/dose as needed based on response to initial dose and as determined by changes in vital signs indicating surgical stress or lightening of anesthesia; data based on experience in cardiac surgery, which requires much higher induction and maintenance doses; lower dosing may be sufficient for other procedures (Coté 2013; Moore 1985).

Epidural: Limited data available: Infants ≥3 months and Children: Epidural injection: Initial bolus: 0.2 mcg/kg followed by continuous infusion at 0.1 mcg/kg/hour in combination with ropivacaine (Woloszczuk-Gebicka 2014)

Procedural/preoperative sedation: Limited data available: Children ≥3 years: Intranasal: 1 to 3 mcg/kg in combination with other agents (Bayrak 2007; Coté 2013; Henderson 1988; Hitt 2014; Lundeberg 2011; Roelofse 2004)

Dosing: Obesity

IV: In adult obese patients (eg, >20% above ideal body weight), use lean body weight to determine dosage.

Administration

IV: Intermittent doses may be administered IV as either a slow injection (eg, over at least 2 minutes [Sebel 1982] or a range of 2 to 10 minutes [Miller 2010]) or as an infusion. May also be administered as a continuous infusion.

Oral: Sublingual tablet: Administer by a health care provider in a certified medically supervised health care setting only. Wear gloves when administering. Tablet is packaged in a single-dose applicator; do not open until ready to administer. Patient should open their mouth and touch their tongue to roof of mouth. Using the single-dose applicator, administer into sublingual space. Patient should not chew or swallow tablet; do not eat or drink and minimize talking for 10 minutes after administration. Refer to manufacturer’s labeling for additional information.

Storage

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

Sublingual tablet: Store at 20°C to 25°C (68°F to 77°F); excursions permitted at 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. 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

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

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

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

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

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. Exceptions are discussed in separate monographs. 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. Consider therapy modification

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of SUFentanil. Monitor therapy

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

CYP3A4 Inhibitors (Strong): May increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Consider therapy modification

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

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

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

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

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

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

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

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

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

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

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. 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

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

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

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors: SUFentanil may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Avoid combination

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

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. 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

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

PHENobarbital: May enhance the CNS depressant effect of SUFentanil. PHENobarbital may decrease the serum concentration of SUFentanil. Management: Avoid use of sufentanil and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined. Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

Primidone: May enhance the CNS depressant effect of SUFentanil. Primidone may decrease the serum concentration of SUFentanil. Management: Avoid use of sufentanil and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

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

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. 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

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. 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

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

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

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Headache (12%)

Dermatologic: Pruritus (epidural administration with bupivacaine: 25%)

Gastrointestinal: Nausea (29%)

1% to 10%:

Cardiovascular: Hypotension (5%)

Central nervous system: Dizziness (6%)

Gastrointestinal: Vomiting (6%)

Frequency not defined:

Cardiovascular: Bradycardia, ECG abnormality, flushing, hypertension, orthostatic hypotension, oxygen saturation decreased, peripheral vasodilation, presyncope, sinus tachycardia, syncope

Central nervous system: Agitation, anxiety, confusion, disorientation, drowsiness, drug abuse, drug dependence, euphoria, hallucination, insomnia, lethargy, memory impairment, mental status changes, sedation

Dermatologic: Hyperhidrosis, skin rash

Gastrointestinal: Abdominal distension, abdominal distress, constipation, decreased gastrointestinal motility, diarrhea, dyspepsia, eructation, flatulence, gastritis, hiccups, intestinal obstruction (postoperative), oral hypoesthesia, retching, upper abdominal pain, xerostomia

Genitourinary: Decreased urine output, oliguria, urinary hesitancy, urinary retention

Hepatic: Increased liver enzymes, increased serum aspartate aminotransferase

Neuromuscular & skeletal: Muscle rigidity, muscle spasm

Ophthalmic: Miosis

Renal: Renal failure syndrome

Respiratory: Apnea, atelectasis, bradypnea, hypoventilation, hypoxia, respiratory depression, respiratory distress, respiratory failure

<1%, postmarketing, and/or case reports: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).
• Bradyarrhythmias: Severe bradycardia may occur; use with caution in patients with bradyarrhythmias.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute myocardial infarction), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Use injection with caution in patients with circulatory shock. Avoid use of sublingual tablets in patients with circulatory shock.
• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur with use of sufentanil. Monitor for respiratory depression, especially during initiation of sufentanil 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 sufentanil and serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, 5-HT receptor antagonists, mirtazapine, trazodone, tramadol) and agents that impair metabolism of serotonin (eg, monoamine oxidase 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 sufentanil if serotonin syndrome is suspected.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Use of sublingual tablets is contraindicated with known or suspected GI obstruction, including paralytic ileus.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.
• CNS depression/coma: Use with caution in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO₂ retention.
• Delirium tremens: Use opioids 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 and reduce dose as needed in patients with hepatic impairment.
• Obesity: Use with caution in patients who are morbidly obese. Consider use of lean body weight for dosing in patients >20% over ideal body weight.
• Prostatic hyperplasia/urinary stricture: Use opioids with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychosis: Use opioids with caution in patients with toxic psychosis.
• Renal impairment: Use with caution and reduce dose as needed 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.
• 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 opioids 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 sufentanil, the dose of other CNS depressant drugs should be reduced.
• CYP3A4 interactions: Use with all CYP3A4 inhibitors may result in an increase in sufentanil 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 sufentanil concentrations. Monitor patients receiving sufentanil 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.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.
• Neonates: Neonatal opioid withdrawal syndrome: Prolonged use of opioids during pregnancy can cause neonatal opioid withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. Observe newborns for signs and symptoms of neonatal opioid withdrawal syndrome. Signs and symptoms include irritability, hyperactivity, and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn. 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.
• Pediatric: Use caution in neonates as clearance of sufentanil is much slower than adults; neonates with cardiovascular disease have an even slower clearance. The clearance of sufentanil in children 2 to 8 years of age was shown to be twice as rapid as that seen in adults and adolescents (Lundeberg 2011).

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Sufentanil 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 sufentanil and monitor all patients regularly for the development of these behaviors and conditions. Use with caution in patients with a personal or family history of drug abuse or acute alcoholism or mental illness; potential for drug dependency exists.
• Accidental exposure (sublingual tablet): [US Boxed Warning]: Accidental exposure to or ingestion of sufentanil, especially in children, can result in respiratory depression and death.
• Appropriate use: Epidural: Proper placement of the needle or catheter in the epidural space should be verified before injection to assure that unintentional intravascular or intrathecal administration does not occur. Unintentional intravascular injection may result in a potentially serious overdose, including acute truncal muscular rigidity and apnea. Unintentional intrathecal injection of the full sufentanil/bupivacaine epidural doses and volume may produce effects of high spinal anesthesia, including prolonged paralysis and delayed recovery.
• Rapid infusion: Injection: Inject slowly over at least 2 minutes (Sebel 1982); rapid IV infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required.
• REMS program (sublingual tablet): [US Boxed Warning]: Because of the potential for life-threatening respiratory depression due to accidental exposure, sufentanil is only available through a restricted program called the REMS Program. Sufentanil must only be dispensed to patients in a certified medically supervised health care setting. Discontinue use of sufentanil prior to discharge or transfer from the certified medically supervised health care setting. Information about the REMS program is available by calling 1-855-925-8476 or at www.DSUVIAREMS.com.
• Trained individuals: Injection: Sufentanil should be administered by 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; resuscitative and intubation equipment should be readily available.

Monitoring Parameters

Pain relief, respiratory and cardiovascular status, blood pressure, and heart rate

Pregnancy

Pregnancy Considerations

Sufentanil crosses the placenta (Cuypers 1995; Loftus 1995).

According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]). Opioids used as part of obstetric analgesia/anesthesia during labor and delivery may temporarily affect the fetal heart rate (ACOG 209 2019).

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. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Opioids may cause respiratory depression and psychophysiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.

Sufentanil injection is commonly used to treat maternal pain during labor and immediately postpartum (ACOG 209 2019). Administration of epidural sufentanil with bupivacaine with or without epinephrine is indicated for use in labor and delivery. Sufentanil tablets are not recommended for use during or immediately before labor.

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

• Nausea
• Vomiting
• Headache
• Itching

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

• 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.
• Noisy breathing
• Chest pain
• Fast heartbeat
• Severe fatigue
• Severe dizziness
• Passing out
• Confusion
• Trouble breathing
• Slow breathing
• Shallow breathing
• Seizures
• Slow heartbeat
• Sexual dysfunction (males)
• No menstrual periods
• Decreased sex drive
• Trouble getting pregnant
• 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.