SUFentanil (Monograph)

Brand name: Dsuvia
Drug class: Opioid Agonists

Medically reviewed by Drugs.com on Nov 20, 2023. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for sufentanil sublingual tablets (Dsuvia) to ensure that the benefits outweigh the risks. The REMS consists of the following: elements to assure safe use and implementation system. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Warning

Risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and monitor regularly for these behaviors and conditions.

Accidental ingestion or exposure to even one dose of sufentanil sublingual tablets, especially in children, can result in respiratory depression and death due to an overdose.
Because of this risk, Dsuvia (sufentanil sublingual tablets) is available only through a restricted distribution program called the Dsuvia REMS.
Administer only by a healthcare provider in a certified medically supervised healthcare setting. Discontinue use prior to discharge or transfer from the certified medically supervised setting.

Serious, life-threatening or fatal, respiratory depression may occur. Monitor closely, especially during titration.

Concomitant use with a CYP3A4 inhibitor may increase plasma concentrations of sufentanil; this may prolong opioid adverse reactions and may exacerbate fatal respiratory depression. Conversely, concomitant use with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could result in lower than expected sufentanil plasma concentrations, and decrease efficacy or result in withdrawal syndrome in patients with physical dependence.

Concomitant use of sufentanil and benzodiazepines or other CNS depressants may result in hypotension or decreased pulmonary arterial pressure; even relatively small dosages of diazepam may cause cardiovascular depression when used with high or anesthetic dosages of sufentanil.

Introduction

Synthetic phenylpiperidine derivative opiate agonist.

Uses for SUFentanil

Analgesic Adjunct to General Anesthesia

Sufentanil injection is used as an IV analgesic adjunct in the maintenance of balanced general anesthesia in adult and pediatric patients who are intubated and ventilated.

Opioids contribute to the primary clinical outcomes of general anesthesia (autonomic nervous system control, unconsciousness, amnesia, and immobility), and are therefore used in balanced anesthesia and multimodal general anesthesia approaches.

Perioperative Anesthesia

Sufentanil injection is used as a primary IV anesthetic agent in conjunction with 100% oxygen for induction and maintenance of anesthesia in patients undergoing major surgical procedures who are intubated and ventilated; the drug is used to provide favorable myocardial and cerebral oxygen balance or when extended postoperative ventilation is anticipated.

Epidural Analgesia

Sufentanil injection is used for epidural administration as an analgesic combined with low dose bupivacaine, usually 12.5 mg per administration, during labor and vaginal delivery. Sufentanil and bupivacaine should be mixed together before administration.

Guidelines for obstetric anesthesia state that opioids, including sufentanil, may be used alone or added to a local anesthetic to reduce the concentration of local anesthetic, improve analgesia, and minimize motor block.

Acute Severe Pain

Sufentanil sublingual tablets (Dsuvia) are used in adults in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments, for management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Experts recommend oral instead of IV opioids for management of postoperative pain in patients who can tolerate oral therapy, and that immediate-release oral formulations are preferred over long-acting or extended-release oral formulations. The lowest effective dosage and duration should be used.

SUFentanil Dosage and Administration

General

Pretreatment Screening

Evaluate and screen for behaviors and conditions indicating risk of addiction, abuse, and misuse prior to initiating therapy.

Patient Monitoring

Monitor for behaviors and conditions indicating risk of addition, abuse, and misuse during therapy.
Monitor vital signs routinely during administration of sufentanil citrate injection; ensure facilities for postoperative monitoring and assisted or controlled respiration are available following administration of anesthetic doses of the drug (i.e., 8 mcg/kg or greater).
Monitor for severe cardiovascular depression (e.g., severe bradycardia, hypotension) during initiation and titration.
Monitor patients who may be susceptible to the effects of increased intracranial pressure.
Monitor patients with biliary tract disease for worsening symptoms.
Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

Dispensing and Administration Precautions

Handling and Disposal:Wear gloves when administering sufentanil sublingual tablets.
Sufentanil injection should be used only by individuals experienced in the use of parenteral anesthetics and in the maintenance of adequate airway and respiratory support. Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available whenever sufentanil is used. An opiate antagonist (e.g., naloxone) should be readily available.
Because of the risk of life-threatening respiratory depression, sufentanil sublingual tablets should only be administered by a healthcare provider in a certified medically supervised healthcare setting, such as a hospital, surgical center, or emergency department. Treatment must be continued prior to the patient leaving the certified medically supervised setting.
Based on the Institute for Safe Medication Practices (ISMP), opioids are high-alert medications that have a heightened risk of causing significant patient harm when used in error.

REMS

Sufentanil sublingual tablets are only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Dsuvia REMS Program because of the potential for life-threatening respiratory depression due to accidental exposure.
Healthcare settings must be able to manage an acute opioid overdose, train all relevant staff regarding dispensation and administration, and establish processes to verify that dispensation outside of the certified healthcare setting does not occur.
Wholesalers must establish processes to ensure distribution of sufentanil sublingual tablets only to certified healthcare settings.

Administration

Sufentanil is administered IV or epidurally, or as sublingual tablets (Dsuvia).

Parenteral Administration

Administer by IV injection, intermittent or continuous IV infusion, or epidural injection. Also has been administered by IM injection^{† [off-label]}.

To administer small volumes of sufentanil injection accurately, the use of a tuberculin syringe or equivalent is recommended.

Sublingual Administration

Administer only by a healthcare provider in a certified medically supervised healthcare setting, such as a hospital, surgical center, or emergency department. Discontinue treatment prior to the patient leaving the certified medically supervised setting. Instruct patients to not chew or swallow sufentanil sublingual tablets. Instruct patients to not eat or drink and to minimize talking for 10 minutes after receiving sufentanil sublingual tablets.

Do not use sufentanil sublingual tablets if the product pouch seal is broken or if the Single-Dose Applicator (SDA) is damaged. Wear gloves when administering sufentanil sublingual tablets.

If a patient experiences excessive dry mouth with sufentanil sublingual tablets, provide ice chips prior to administration.

Dosage

Dosage of sufentanil citrate is expressed in terms of sufentanil. Adjust dosage based on individual requirements and indication.

Pediatric Patients

Perioperative Anesthesia

IV

Children <12 years of age undergoing cardiovascular surgery: Initially, 10–25 mcg/kg in conjunction with 100% oxygen and a skeletal muscle relaxant. Additional doses of up to 25–50 mcg each may be given as needed based on response to the initial dose and as determined by changes in vital signs that indicate surgical stress or lightening of anesthesia.

Adults

Analgesic Adjunct to General Anesthesia

IV

Minor surgical procedures (expected duration of anesthesia is 1–2 hours): Total dosage of 1–2 mcg/kg in conjunction with nitrous oxide and oxygen; ≥75% of the total dosage may be given by slow injection or infusion prior to intubation. May administer supplemental doses of 10–25 mcg or administer intermittent or continuous maintenance infusions as necessary when movement and/or changes in vital signs indicate surgical stress or lightening of anesthesia; adjust maintenance infusion rate so that total dosage does not exceed 1 mcg/kg per hour of expected surgical time.

Major surgical procedures (expected duration of anesthesia is 2–8 hours): Total dosage of 2–8 mcg/kg in conjunction with nitrous oxide and oxygen; ≤75% of the total dosage may be given by slow injection or infusion prior to intubation. May administer supplemental doses of 10–50 mcg or administer intermittent or continuous maintenance infusions as necessary when movement and/or changes in vital signs indicate surgical stress or lightening of anesthesia; adjust maintenance infusion rate so that total dosage does not exceed 1 mcg/kg per hour of expected surgical time.

Perioperative Anesthesia

IV

Total dosage of 8–30 mcg/kg (by slow injection, infusion, or injection followed by infusion) in conjunction with oxygen and a skeletal muscle relaxant. Depending on the initial dose, may administer additional incremental doses of 0.5–10 mcg/kg by slow injection in anticipation of surgical stress (e.g., incision, sternotomy, cardiopulmonary bypass). Alternatively, may administer intermittent or continuous maintenance infusions as necessary as determined by changes in vital signs that indicate surgical stress and lightening of anesthesia; adjust maintenance infusion rate so that total dosage for the procedure does not exceed 30 mcg/kg.

Epidural Analgesia

Epidural

10–15 mcg (in combination with 10 mL of bupivacaine 0.125% with or without epinephrine). Doses may be repeated twice (for a total of 3 doses) at ≥1-hour intervals until delivery.

Acute Severe Pain

Sublingual

30 mcg sublingually as needed with a minimum of 1 hour between doses; maximum 12 tablets (360 mcg) per 24 hours.

Special Populations

Hepatic Impairment

Adjust dosage carefully; elimination of the drug may be decreased.

Renal Impairment

Adjust dosage carefully; elimination of the drug may be decreased.

Geriatric Use

Reduce initial dosage; adjust additional doses according to the initial response and desired effect.

Because the dose of sufentanil sublingual tablets cannot be titrated, monitor geriatric patients closely for signs of CNS and respiratory depression or consider an alternate medication that can be titrated.

Cautions for SUFentanil

Contraindications

Hypersensitivity to sufentanil.
Significant respiratory depression (sufentanil sublingual tablets).
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (sufentanil sublingual tablets).
Known or suspected GI obstruction, including paralytic ileus (sufentanil sublingual tablets).

Warnings/Precautions

Warnings

Addiction, Abuse, and Misuse

Sufentanil is a Schedule II controlled substance, which exposes users to the risks of addiction, abuse, and misuse (see Boxed Warning). Consider these risks when prescribing and dispensing sufentanil.

Accidental Exposure to Sublingual Tablets

Accidental ingestion or exposure to sufentanil sublingual tablets, especially in children, can result in respiratory depression and death due to an overdose (see Boxed Warning). Sufentanil sublingual tablets are for use in adult patients only in a certified medically supervised healthcare setting, consistent with the REMS program.

Life-Threatening Respiratory Depression

Can severely compromise respiratory function (see Boxed Warning). Risk of serious respiratory depression due to sufentanil sublingual tablets is greatest during initiation of therapy. Risk is also increased in elderly, cachectic, or debilitated patients, who may have altered pharmacokinetics or altered clearance of sufentanil. In patients who present with central sleep apnea, consider decreasing the opioid dosage using best practices for opioid taper. .

Monitor patients closely throughout treatment. Risk of decreased respiratory drive is increased in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression.

Sufentanil injection should be used onlyby individuals experienced in the use of parenteral anesthetics and in the maintenance of an adequate airway and respiratory support. Facilities and personnel necessary for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available. An opiate antagonist (e.g., naloxone) should be readily available. Monitor vital signs routinely; facilities for postoperative monitoring and assisted or controlled respiration should be available following administration of anesthetic doses of the drug (i.e., 8 mcg/kg or greater).

Concomitant Use or Discontinuation of CYP3A4 Inhibitors and Inducers

Concomitant use with a CYP3A4 inhibitor may increase plasma concentrations of sufentanil; this may prolong opioid adverse reactions and cause potentially fatal respiratory depression (see Boxed Warning). Similarly, discontinuation of a CYP3A4 inducer in sufentanil-treated patients may increase sufentanil plasma concentrations and prolong opioid adverse reactions.

When using sufentanil with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in sufentanil-treated patients, monitor patients closely and consider dosage reduction of sufentanil. Concomitant use with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could result in lower than expected sufentanil plasma concentrations, and decrease efficacy or result in withdrawal syndrome. When using sufentanil with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely and consider increasing the dosage of sufentanil.

Concomitant use with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could result in lower than expected sufentanil plasma concentrations, and decrease efficacy or result in withdrawal syndrome. When using sufentanil with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely and consider increasing the dosage of sufentanil.

Concomitant Use With Benzodiazepines or Other CNS Depressants

Concomitant use with benzodiazepines or other CNS depressants may result in hypotension or decreased pulmonary arterial pressure (see Boxed Warning). If hypotension occurs with use of sufentanil injection, consider possibility of hypovolemia and manage with appropriate fluid therapy. Consider repositioning patient to improve venous return to the heart. If volume expansion and other countermeasures do not correct hypotension, consider administration of a pressor agent (other than epinephrine).

Concomitant use with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate. If concomitant use is necessary, start with lowest effective dosage, titrate based on clinical response, and monitor closely for signs and symptoms of respiratory depression, sedation, and hypotension.

Muscle Rigidity and Skeletal Muscle Movement

Muscle rigidity, particularly involving the muscles of respiration, may occur with IV administration or unintentional intravascular injection during epidural administration of sufentanil. Skeletal muscle rigidity may also occur or recur in the extended postoperative period, usually following high doses of sufentanil. Skeletal muscle movements may also occur during induction of anesthesia with sufentanil.

Severe Cardiovascular Depression

May cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope. Risk is increased in patients whose ability to maintain BP has already been compromised.

In patients with circulatory shock, sufentanil may cause vasodilation that can further reduce cardiac output and blood pressure. Monitor these patients for hypotension after initiating or titrating sufentanil dosages; avoid use of sufentanil sublingual tablets in patients with circulatory shock.

Monitor patients with bradyarrhythmias for changes in heart rate.

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs

Serotonin syndrome reported during concomitant use with serotonergic drugs. Discontinue sufentanil if serotonin syndrome is suspected.

Improper Epidural Injection

Verify proper placement of the needle or catheter in the epidural space before sufentanil is injected to assure that unintentional intravascular or intrathecal administration does not occur. If analgesia is inadequate, verify the placement and integrity of the catheter prior to administration of any additional epidural medications. Administer sufentanil epidurally by slow injection.

Use in Patients with Increased Intracranial Pressure, Brain Tumors, or Head Injury

May reduce respiratory drive and increase intracranial pressure in patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors). Monitor such patients for signs of increasing intracranial pressure with use of sufentanil injection, and for signs and symptoms of sedation and respiratory depression, particularly when initiating therapy, with sufentanil sublingual tablets.

Use in Patients with GI Conditions

May cause spasm of the sphincter of Oddi. Opioids may increase serum amylase. Monitor for worsening symptoms in patients with biliary tract disease.

Increased Risk of Seizures in Patients with Seizure Disorders

Risk of increased seizure frequency in patients with seizure disorders. Monitor patients for seizure control during treatment.

Risks of Driving and Operating Machinery

May impair the ability to perform potentially hazardous activities. Warn patients not to engage in such behaviors after sufentanil administration.

Adrenal Insufficiency

Adrenal insufficiency reported with opioid use, generally following >1 month of use. If adrenal insufficiency suspected, confirm the diagnosis as soon as possible. If diagnosed, treat with physiologic replacement doses of corticosteroids. Wean patient off the opioid and continue corticosteroid treatment until adrenal function recovers. Consider trials of other opioids.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of sufentanil sublingual tablets during pregnancy can result in withdrawal in the neonate. Observe newborns for signs of neonatal opioid withdrawal syndrome and institute appropriate therapy. Advise pregnant females using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Abuse Potential and Dependence

Sufentanil has high potential for abuse. Also subject to misuse, addiction, and criminal diversion.

Carefully monitor for signs of abuse and addiction. Abuse can be limited with proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage.

Both tolerance and physical dependence can develop during chronic opioid therapy. Physical dependence can result in withdrawal symptoms following abrupt discontinuation or significant dose reduction.

Specific Populations

Pregnancy

Prolonged use during pregnancy may cause neonatal opioid withdrawal syndrome. No adequate data on sufentanil in pregnant females.

Sufentanil injection not recommended in pregnant females during or immediately prior to labor, when other analgesic techniques are more appropriate. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Epidural administration of sufentanil in combination with bupivacaine 0.125% with or without epinephrine is indicated for labor and delivery. Sufentanil is not recommended for IV use or for use of larger epidural doses during labor and delivery because of potential risks to the newborn infant after delivery.

Lactation

Monitor infants exposed to sufentanil through breast milk for excess sedation and respiratory depression.

Females and Males of Reproductive Potential

Reduced fertility may occur with chronic use of opioids. Not known whether these effects are reversible.

Pediatric Use

Safety and efficacy of sufentanil injection in children as young as 1 day of age based on a limited number of patients undergoing cardiovascular surgery. Safety and efficacy of sufentanil sublingual tablets in pediatric patients not established; use not recommended.

Clearance of sufentanil in healthy neonates is approximately one-half that in adults and children; can be further reduced by up to a third in neonates with cardiovascular disease.

Geriatric Use

No studies in geriatric patients conducted with sufentanil sublingual tablets. Use caution when selecting dosage, usually starting at the low end of dosing range. Titrate dosage slowly in geriatric patients and monitor closely for signs of CNS and respiratory depression.

Hepatic Impairment

Use with caution due to extensive hepatic metabolism.

Renal Impairment

Use with caution due to renal excretion.

Common Adverse Effects

Most common adverse reactions with sufentanil citrate injection: respiratory depression, apnea, rigidity, bradycardia.

Most common adverse reactions (≥2%) with sufentanil sublingual tablets: nausea, headache, vomiting, dizziness, hypotension.

Drug Interactions

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors:can increase plasma concentration of sufentanil, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after achieving a stable dose of sufentanil. After stopping a CYP3A4 inhibitor, the sufentanil plasma concentration will decrease as the effects of the inhibitor decline; this may result in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to sufentanil. If sufentanil is administered concomitantly with a CYP3A4 inhibitor, consider dosage reduction of sufentanil until stable drug effects are achieved, and monitor for respiratory depression and sedation. If concomitant use is necessary, consider an alternate medication to sufentanil sublingual tablets that allows dose titration. If a concomitant CYP3A4 inhibitor is discontinued, consider increasing the dosage of sufentanil until stable drug effects are achieved, and monitor for signs of opioid withdrawal.

CYP3A4 inducers: can decrease plasma concentration of sufentanil, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to sufentanil. After stopping a CYP3A4 inducer, the sufentanil plasma concentration will increase as the effects of the inducer decline, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. If concomitant use is necessary, consider an alternate medication to sufentanil sublingual tablets that allows dose titration. If a CYP3A4 inducer is discontinued, consider sufentanil dosage reduction and monitor for signs of respiratory depression.

Serotonergic Drugs

Concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system can cause serotonin syndrome.

If concomitant use is necessary, monitor patient, particularly during treatment initiation and dose adjustment. Discontinue sufentanil if serotonin syndrome is suspected.

Specific Drugs

Drug	Interaction	Comments
Anticholinergic drugs	Increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.	Monitor for signs of urinary retention and reduced gastric motility.
β-Adrenergic blocking agents	Increased incidence and degree of bradycardia and hypotension during sufentanil-oxygen anesthesia in patients receiving chronic β-blocker therapy
Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, triazolam)	Increased risk of hypotension, decreased pulmonary arterial pressure, profound sedation, respiratory depression, coma, or death; even relatively small diazepam dosages may cause cardiovascular depression if given with high or anesthetic sufentanil dosages	If hypotension occurs, consider possibility of hypovolemia and manage as clinically appropriate (e.g., IV fluids, repositioning of patient to improve venous return, pressor therapy) Consider potential for decreased pulmonary arterial pressure when performing diagnostic or surgical procedures where interpretation of such measurements might determine patient management If used for postoperative analgesia, initiate sufentanil at reduced dosage and titrate based on clinical response; monitor closely for hypotension, respiratory depression, and sedation and ensure measures (e.g., fluids) to counteract hypotension are available
Calcium-channel blocking agents	Increased incidence and degree of bradycardia and hypotension during sufentanil-oxygen anesthesia in patients receiving chronic calcium-channel blocker therapy
CNS depressants (e.g., other opiate agonists, antipsychotics, anxiolytics, general anesthetics, tranquilizers, alcohol)	Potentiation of CNS and cardiovascular effects; increased risk of hypotension, decreased pulmonary arterial pressure, profound sedation, respiratory depression, coma, or death	If hypotension occurs, consider possibility of hypovolemia and manage as clinically appropriate (e.g., IV fluids, repositioning of patient to improve venous return, pressor therapy) Consider potential for decreased pulmonary arterial pressure when performing diagnostic or surgical procedures where interpretation of such measurements might determine patient management If used for postoperative analgesia, initiate sufentanil at reduced dosage and titrate based on clinical response; monitor closely for hypotension, respiratory depression, and sedation and ensure measures (e.g., fluids) to counteract hypotension are available
Diuretics	Reduced efficacy of diuretics due to opioid-induced release of antidiuretic hormone	Monitor for signs of diminished diuresis and/or effects on blood pressure; increase the dosage of diuretics as needed
MAO inhibitors (e.g., isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, tranylcypromine)	Risk of serotonin syndrome	Sufentanil not recommended for patients taking MAO inhibitors or within 14 days of stopping such treatment.
Mixed agonist/antagonist and partial agonist opioid analgesics	Reduced analgesic effect of sufentanil and/or precipitation of withdrawal symptoms.	Avoid concomitant use.
Nitrous oxide	Possible cardiovascular depression, manifested by bradycardia and decreases in mean arterial pressure and cardiac output, following concomitant administration of nitrous oxide with high doses of sufentanil
Sedative/hypnotic agents (e.g., butabarbital, eszopiclone, pentobarbital, ramelteon, secobarbital, suvorexant, zaleplon, zolpidem)	Increased risk of hypotension, decreased pulmonary arterial pressure, profound sedation, respiratory depression, coma, or death	If hypotension occurs, consider possibility of hypovolemia and manage as clinically appropriate (e.g., IV fluids, repositioning of patient to improve venous return, pressor therapy) Consider potential for decreased pulmonary arterial pressure when performing diagnostic or surgical procedures where interpretation of such measurements might determine patient management If used for postoperative analgesia, initiate sufentanil at reduced dosage and titrate based on clinical response; monitor closely for hypotension, respiratory depression, and sedation and ensure measures (e.g., fluids) to counteract hypotension are available
Skeletal muscle relaxants (e.g., baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine)	Risk of increased degree of respiratory depression.	Monitor for signs and symptoms of respiratory depression that may be greater than otherwise expected; if respiratory depression occurs with concomitant use of sufentanil sublingual tablets and a skeletal muscle relaxant, consider decreasing the dose of the skeletal muscle relaxant or discontinuing sufentanil.

SUFentanil Pharmacokinetics

Absorption

Onset

Following IV administration, the onset of action as determined by time to unconsciousness (i.e., loss of response to voice command) is 1.2–3 minutes.

Following epidural administration of 10–15 mcg and 0.125% bupivacaine with epinephrine 1:200,000 during the first stage of labor, the onset of action occurs within 10 minutes.

Following a single sublingual administration, sufentanil has a bioavailability of approximately 53% relative to a 1-minute IV sufentanil infusion of 30 mcg. Following a single dose of sufentanil sublingual tablets, maximum concentrations occur at a median time of 1 hour.

Duration

The mean duration of anesthesia is 40 minutes following initial IV dose of 0.4 mcg/kg and 41–44 minutes following additional doses of 0.1 mcg/kg.

Duration of analgesia following a single epidural injection of 10–15 mcg sufentanil citrate and bupivacaine 0.125% averaged 1–2 hours.

Distribution

Extent

Distribution into human body tissues and fluids has not been fully characterized; however, the drug is highly lipophilic and is rapidly and extensively distributed in animals.

Not known whether sufentanil crosses the placenta or distributes into human milk.

Plasma Protein Binding

Approximately 93% bound at plasma pH 7.4 (mainly to albumin; α-, α₁-, β-, and γ-globulins; and α₁-acid glycoprotein).

Elimination

Metabolism

Appears to be metabolized mainly in the liver and small intestine via N-dealkylation and O-demethylation.

The O-demethylated metabolite appears to have about 10% of the analgesic activity of the unchanged drug.

Elimination Route

Excreted principally in urine and also in feces via biliary elimination; only 2% of a dose is excreted unchanged in urine and feces.

Half-life

Triphasic; plasma concentrations decline rapidly secondary to redistribution.

In adults with normal renal and hepatic function, the plasma half-life averages 0.72–1.2 minutes in the initial (distribution) phase, 13.7–17 minutes in the second (redistribution) phase, and 140–158 minutes in the terminal (elimination) phase.

Elimination half-life is longer (434 minutes) in neonates but shorter in infants and children (97 minutes), compared with adults (164 minutes).

Following a single dose of sufentanil sublingual tablets, the mean terminal half-life is 13.4 hours.

Stability

Storage

Parenteral

Injection

20–25°C; protect from light.

Sublingual

Tablets

20–25 ºC (excursions permitted to 15–30 ºC).

Actions

A potent analgesic; shares the actions of the opiate agonists. Sufentanil produces dose-related analgesia; at doses up to 8 mcg/kg, the drug has a potent analgesic effect. Higher doses usually produce substantial CNS depression resulting in hypnosis and anesthesia.
High affinity and selectivity for the μ-opiate receptor in the CNS; reportedly is more selective and binds more tightly to this receptor than does fentanyl.
Analgesic potency appears to be 5–12 times that of fentanyl on a weight basis.
Appears to have little effect on histamine release.
May have a centrally mediated vagal effect.

Advice to Patients

Inform patients that accidental exposure to sufentanil sublingual tablets, especially by children, may result in respiratory depression or death.
Inform patients of the risk of life-threatening respiratory depression, including that the risk is greatest when starting sufentanil sublingual tablets.
Inform patients that the use of sufentanil sublingual tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death. Instruct patients not to share sufentanil sublingual tablets with others and to take steps to guard against theft or misuse.
Inform patients of the risk for and symptoms of serotonin syndrome. Advise patients to seek immediate medical attention if symptoms develop, and to inform their physicians if they are taking, or plan to take serotonergic medications.
Inform patients that opioids could cause adrenal insufficiency. Advise patients to seek medical attention if they experience signs or symptoms of adrenal insufficiency, including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
Advise patients to allow sufentanil sublingual tablets to dissolve under the tongue and not to chew or swallow the tablet. Advise patients not to eat or drink and to minimize talking for 10 minutes after each sublingual dose.
Inform patients that sufentanil sublingual tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position).
Inform patients that anaphylaxis has been reported with ingredients contained in sufentanil sublingual tablets. Advise patients how to recognize such a reaction and when to seek medical attention.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Inform female patients of reproductive potential that sufentanil sublingual tablets can (or may) cause fetal harm and to inform the prescriber of a known or suspected pregnancy.
Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

SUFentanil Citrate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV and epidural use	50 mcg (of sufentanil) per mL*	SUFentanil Citrate Injection ( C-II )
Sublingual	Tablets	30 mcg (of sufentanil)	Dsuvia (C-II; available in a single-dose applicator)