Sufentanil Citrate

Name: Sufentanil Citrate

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Uses for Sufentanil Citrate

Anesthesia

As the analgesic component in the maintenance of balanced anesthesia (e.g., IV hypnotic and/or inhalation anesthetic, analgesic, skeletal muscle relaxant).1 17 34 36 41 46

As the primary anesthetic agent for induction and maintenance of general anesthesia when used in conjunction with 100% oxygen and a skeletal muscle relaxant (e.g., pancuronium bromide, succinylcholine chloride).1 10 11 12 13 15 16 18 35 37 38 39 43 44 45

Particularly useful when postoperative ventilation is anticipated and in providing favorable myocardial and cerebral oxygen balance.1 11 19 40 41 46

Cardiovascular parameters generally are more stable intraoperatively with use of sufentanil compared with inhalation agents.36 41 Incidence of postoperative hypertension and requirements for vasoactive agents or postoperative analgesics generally are decreased following use of moderate or high doses of sufentanil as compared with use of inhalation agents.1 36 38 41

Pain

Obstetric analgesia during labor and vaginal delivery.1 88

Cautions for Sufentanil Citrate

Contraindications

Known hypersensitivity to sufentanil or intolerance to other opiate agonists.1

Warnings/Precautions

Warnings

Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.1 4

Respiratory Depression

Respiratory function can be severely compromised.1

Consider the possibility of a recurrence of respiratory depression during recovery.4 A secondary rise in plasma concentrations may occur during the recovery period as blood perfusion to peripheral tissues increases and drug redistribution occurs.4

Administration of an opiate antagonist (e.g., naloxone) can reverse respiratory depression.1 The duration of respiratory depression produced by sufentanil may be longer than the duration of the opiate antagonist; therefore, continue appropriate patient monitoring following apparent initial reversal.1

Supervised Administration

Should be administered only by individuals experienced in the use of parenteral anesthetics and in the maintenance of an adequate airway and respiratory support.1

Opiate antagonist (e.g., naloxone) and facilities for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.1

Monitor vital signs routinely during administration; 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).1

Major Toxicities

Musculoskeletal Effects

Possible skeletal muscle rigidity (e.g., of the truncal muscles); onset may be more rapid than with fentanyl.1 Administration of a neuromuscular blocking agent may be necessary.1 (See Concomitant Administration of a Neuromuscular Blocking Agent under Dosage and Administration.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.400 Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.400

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.400 If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.400 In some patients, switching to a different opiate improved symptoms.400

General Precautions

CNS Effects

Caution in patients with head injuries; sufentanil may obscure the clinical course.1

Impaired Respiration

Caution in patients with pulmonary disease, decreased respiratory reserve, or potentially compromised respiratory function.1 Further decreases in respiratory function and increases in airway resistance may occur.1

Cardiovascular Effects

Generally produces few cardiovascular effects.4 8 13 17 39 Possible hypotension1 8 10 34 36 39 40 or hypertension.1 8 10 18 35 37 38 40 41 42 Bradycardia occurs infrequently during anesthesia and may be corrected by administration of atropine.1

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;400 401 402 403 404 causality not established.400 Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.400 Perform appropriate laboratory testing in patients with manifestations of hypogonadism.400

Specific Populations

Pregnancy

Category C.1

Used epidurally for analgesia during labor and delivery.1 88 Not recommended for IV use during labor and delivery; avoid epidural dosages in excess of the recommended dosage.1

Lactation

Not known whether sufentanil is distributed into milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy documented in a limited number of children ≥1 day of age undergoing cardiovascular surgery.1 8 89

Use with caution in neonates because decreased clearance may result in increased blood concentrations of the drug.89 Clearance in healthy neonates is approximately one-half that reported in adults and children; may be further reduced by up to one-third in neonates with cardiovascular disease.89

Geriatric Use

Consider dosage reduction.1 61 (See Geriatric and Debilitated Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution, since the drug undergoes metabolism in the liver.1

Renal Impairment

Use with caution, since the drug and its metabolites are eliminated mainly by the kidneys.1

Common Adverse Effects

Respiratory depression,1 38 skeletal muscle rigidity (e.g., truncal muscles, neck, extremities).1 4 13 38

Actions

A potent analgesic;1 shares the actions of the opiate agonists.1 4 29
Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.b
Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).26 b
Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.26
Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.b
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.4 9 12 25 49 52
Produces dose-related analgesia;1 2 4 at doses up to 8 mcg/kg, the drug has a potent analgesic effect, but higher doses usually produce substantial CNS depression resulting in hypnosis and anesthesia.1 2 4 9 10 11 12 13 19
Analgesic potency appears to be 5–12 times that of fentanyl on a weight basis.1 12 23 39 40 47 48 50
Appears to have little effect on histamine release.1 7 53 54 61
May have a centrally mediated vagal effect.4 60 61

Sufentanil Citrate Dosage and Administration

Important Dosage and Administration Instructions

Sufentanil Citrate Injection should be administered only by persons specifically trained in the use of intravenous or epidural anesthetics and management of the respiratory effects of potent opioids.

In patients administered high doses of Sufentanil Citrate Injection, it is essential that qualified personnel and adequate facilities are available for the management of postoperative respiratory depression.

For purposes of administering small volumes of Sufentanil Citrate Injection accurately, the use of a tuberculin syringe or equivalent is recommended.

Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available.
Individualize dosage based on factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.
Monitor vital signs regularly.
The selection of preanesthetic medications should be based upon the needs of the individual patient.
The neuromuscular blocking agent selected should be compatible with the patient's condition, taking into account the hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required.

As with other potent opioids, the respiratory depressant effect of sufentanil may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia.

If Sufentanil Citrate Injection is administered with a CNS depressant, become familiar with the properties of each drug, particularly each product's duration of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available [see Warnings and Precautions (5.5)].

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Intravenous use

Sufentanil Citrate may be administered intravenously by slow injection or infusion.

Adjunct to general anesthesia:

Doses of up to 8 mcg/kg (see Table 1)
Total Dosage Requirements Of 1 Mcg/Kg/Hr Or Less Are Recommended
Dosage should be individualized and adjusted to remaining operative time anticipated.

Table 1: Adult Dosage Range Chart, Analgesic Component To General Anesthesia, Intravenous Use

Total dosage	Maintenance dosage
Duration of anesthesia 1 to 2 hours
Incremental or Infusion: 1 to 2 mcg/kg Approximately 75% or more of total sufentanil dosage may be administered prior to intubation by either slow injection or infusion titrated to individual patient response. Dosages in this range are generally administered with nitrous oxide/oxygen in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.	Incremental: 10 to 25 mcg (0.2 to 0.5 mL) may be administered in increments as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Supplemental dosages should be individualized and adjusted to remaining operative time anticipated. Infusion: Intermittent or continuous infusion as needed in response to signs of lightening of analgesia. In absence of signs of lightening of analgesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation. Maintenance infusion rates should be adjusted based upon the induction dose of sufentanil so that the total dose does not exceed 1 mcg/kg/hr of expected surgical time.
Duration of anesthesia 2 to 8 hours
Incremental or Infusion: 2 to 8 mcg/kg Approximately 75% or less of the total calculated sufentanil dosage may be administered by slow injection or infusion prior to intubation, titrated to individual patient response. Dosages in this range are generally administered with nitrous oxide/oxygen in patients undergoing more complicated major surgical procedures in which endotracheal intubation and mechanical ventilation are required. At dosages in this range, sufentanil has been shown to provide some attenuation of sympathetic reflex activity in response to surgical stimuli, provide hemodynamic stability, and provide relatively rapid recovery.	Incremental: 10 to 50 mcg (0.2 to 1 mL) may be administered in increments as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Supplemental dosages should be individualized and adjusted to the remaining operative time anticipated. Infusion: Intermittent or continuous infusion as needed in response to signs of lightening of analgesia. In the absence of signs of lightening of analgesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation. Maintenance infusion rates should be adjusted based upon the induction dose of sufentanil so that the total dose does not exceed 1 mcg/kg/hr of expected surgical time.

Induction And Maintenance Of Anesthesia

As the primary anesthetic agent: doses ≥8 mcg/kg (see Dosage Range Chart, Table 2).
Dosage should be titrated to individual patient response
In children less than 12 years of age undergoing cardiovascular surgery: 10 to 25 mcg/kg administered with 100% oxygen
- Supplemental dosages of up to 25 to 50 mcg are recommended for maintenance, based on response to initial dose and as determined by changes in vital signs indicating surgical stress or lightening of anesthesia.

Table 2: Dosage Range Chart, Induction and Maintenance of Anesthesia, Intravenous Use

Incremental or Infusion: 8 to 30 mcg/kg
Generally administered as a slow injection, as an infusion, or as an injection followed by an infusion.
Sufentanil with 100% oxygen and a muscle relaxant has been found to produce sleep at dosages ≥8 mcg/kg and to maintain a deep level of anesthesia without the use of additional anesthetic agents. The addition of N2O to these dosages will reduce systolic blood pressure. At dosages in this range of up to 25 mcg/kg, catecholamine release is attenuated.
Dosages of 25 to 30 mcg/kg have been shown to block sympathetic response including catecholamine release.
High doses are indicated in patients undergoing major surgical procedures, in which endotracheal intubation and mechanical ventilation are required, such as cardiovascular surgery and neurosurgery in the sitting position with maintenance of favorable myocardial and cerebral oxygen balance.
Postoperative observation is essential and postoperative mechanical ventilation may be required at the higher dosage range due to extended postoperative respiratory depression.

Incremental: Depending on the initial dose, maintenance doses of 0.5 to 10 mcg/kg may be administered by slow injection in anticipation of surgical stress such as incision, sternotomy or cardiopulmonary bypass.
Infusion: Sufentanil Citrate may be administered by continuous or intermittent infusion as needed in response to signs of lightening of anesthesia.
In the absence of lightening of anesthesia, infusion rates should always be adjusted downward until there is some response to surgical stimulation.
The maintenance infusion rate for sufentanil should be based upon the induction dose so that the total dose for the procedure does not exceed 30 mcg/kg.

Epidural Use in Labor and Delivery

Proper placement of the needle or catheter in the epidural space should be verified before Sufentanil Citrate is injected to assure that unintentional intravascular or intrathecal administration does not occur. Unintentional intravascular injection of sufentanil could 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 could produce effects of high spinal anesthesia including prolonged paralysis and delayed recovery.

Sufentanil should be administered by slow injection. Respiration should be closely monitored following each administration of an epidural injection of sufentanil.
If analgesia is inadequate, the placement and integrity of the catheter should be verified prior to the administration of any additional epidural medications.

Dosage for Labor and Delivery

10 to 15 mcg administered with 10 mL bupivacaine 0.125% with or without epinephrine.
Sufentanil and bupivacaine should be mixed together before administration.
Doses can be repeated twice (for a total of three doses) at not less than one-hour intervals until delivery.

Warnings and Precautions

Addiction, Abuse, and Misuse

Sufentanil Citrate Injection contains sufentanil, a Schedule II controlled substance. As an opioid, Sufentanil Citrate Injection exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)].

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when handling Sufentanil Citrate Injection. Strategies to reduce these risks include proper product storage and control practices for a C-II drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Sufentanil Citrate Injection should be administered only by persons specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, including respiration and cardiac resuscitation of patients in the age group being treated. Such training must include the establishment and maintenance of a patent airway and assisted ventilation. Adequate facilities should be available for postoperative monitoring and ventilation of patients administered anesthetic doses of Sufentanil Citrate Injection. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

As with other potent opioids, the respiratory depressant effect of Sufentanil Citrate Injection may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia.

Certain forms of conduction anesthesia, such as spinal anesthesia and some epidural anesthetics, can alter respiration by blocking intercostal nerves [see Clinical Pharmacology (12.2)] Sufentanil Citrate Injection can also alter respiration. Therefore, when Sufentanil Citrate Injection is used to supplement these forms of anesthesia, the anesthetist should be familiar with the physiological alterations involved, and be prepared to manage them in the patients selected for these forms of anesthesia.

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 are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Sufentanil Citrate Injection. Elderly, cachectic, or debilitated patients may have altered pharmacokinetics or altered clearance compared to younger, healthier patients resulting in greater risk for respiratory depression.

Monitor such patients closely including vital signs, particularly when initiating and titrating Sufentanil Citrate Injection and when Sufentanil Citrate Injection is given concomitantly with other drugs that depress respiration. To reduce the risk of respiratory depression, proper dosing and titration of Sufentanil Citrate Injection are essential [see Dosage and Administration (2.1)].

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of Sufentanil Citrate Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of sufentanil and prolong opioid adverse reactions, which may exacerbate fatal respiratory depression [see Warnings and Precautions (5.2)], particularly when an inhibitor is added after a stable dose of Sufentanil Citrate Injection is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Sufentanil Citrate Injection-treated patients may increase sufentanil plasma concentrations and prolong opioid adverse reactions. When using Sufentanil Citrate Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Sufentanil Citrate Injection-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Sufentanil Citrate Injection [see Dosage and Administration (2.1), Drug Interactions (7)].

Concomitant use of Sufentanil Citrate Injection with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could result in lower than expected sufentanil plasma concentrations, and decrease efficacy. When using Sufentanil Citrate Injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the Sufentanil Citrate Injection dosage [see Dosage and Administration (2.1), Drug Interactions (7)].

Risks of Muscle Rigidity and Skeletal Muscle Movement

Intravenous administration or unintentional intravascular injection during epidural administration of Sufentanil Citrate Injection may cause muscle rigidity, particularly involving the muscles of respiration. The incidence and severity of muscle rigidity is dose related. These effects are related to the dose and speed of injection. Administration of sufentanil may produce muscular rigidity with a more rapid onset of action than that seen with fentanyl. Skeletal muscle rigidity also has been reported to occur or recur infrequently in the extended postoperative period usually following high dose administration. In addition, skeletal muscle movements of various groups in the extremities, neck, and external eye have been reported during induction of anesthesia with Sufentanil Citrate Injection; these reported movements have, on rare occasions, been strong enough to pose patient management problems.

The incidence of skeletal muscle rigidity can be reduced by: 1) administration of up to 1/4 of the full paralyzing dose of a non-depolarizing neuromuscular blocking agent just prior to administration of sufentanil at dosages of up to 8 mcg/kg, 2) administration of a full paralyzing dose of a neuromuscular blocking agent following loss of consciousness when sufentanil is used in anesthetic dosages (above 8 mcg/kg) titrated by slow intravenous infusion, or, 3) simultaneous administration of sufentanil and a full paralyzing dose of a neuromuscular blocking agent when sufentanil is used in rapidly administered anesthetic dosages (above 8 mcg/kg).

The neuromuscular blocking agents used should be compatible with the patient's cardiovascular status. The hemodynamic effects and degree of skeletal muscle relaxation required should be considered in the selection of a neuromuscular blocking agent. High doses of pancuronium may produce increases in heart rate during sufentanil-oxygen anesthesia. Bradycardia and hypotension have been reported with other muscle relaxants during sufentanil-oxygen anesthesia; this effect may be more pronounced in the presence of calcium channel and/or beta-blockers. Muscle relaxants with no clinically significant effect on heart rate (at recommended doses) would not counteract the vagotonic effect of sufentanil, therefore a lower heart rate would be expected. Rare reports of bradycardia associated with the concomitant use of succinylcholine and sufentanil have been reported.

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

When benzodiazepines or other CNS depressants are used with Sufentanil Citrate Injection, pulmonary arterial pressure may be decreased. This fact should be considered by those who conduct diagnostic and surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient. When high dose or anesthetic dosages of Sufentanil Citrate Injection are employed, even relatively small dosages of diazepam may cause cardiovascular depression.

When Sufentanil Citrate Injection is used with CNS depressants, hypotension can occur. If it occurs, consider the possibility of hypovolemia and manage with appropriate parenteral fluid therapy. When operative conditions permit, consider repositioning the patient to improve venous return to the heart. Exercise care in moving and repositioning of patients because of the possibility of orthostatic hypotension. If volume expansion with fluids plus other countermeasures do not correct hypotension, consider administration of pressor agents other than epinephrine. Epinephrine may paradoxically decrease blood pressure in patients treated with a neuroleptic that blocks alpha adrenergic activity.

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Sufentanil Citrate Injection with benzodiazepines or other CNS depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol).

If the decision is made to manage postoperative pain with Sufentanil Citrate Injection concomitantly with a benzodiazepine or other CNS depressant, start dosing with the lowest effective dosage and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression, sedation, and hypotension. Fluids or other measures to counter hypotension should be available. [see Drug Interactions (7)]

Severe Cardiovascular Depression

Sufentanil Citrate Injection may cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. In patients with circulatory shock, Sufentanil Citrate Injection may cause vasodilation that can further reduce cardiac output and blood pressure. Monitor these patients for signs of hypotension after initiating or titrating the dosage of Sufentanil Citrate Injection.

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of Sufentanil Citrate Injection with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7)]. This may occur within the recommended dosage range.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue Sufentanil Citrate Injection if serotonin syndrome is suspected.

Risks due to Improper Epidural Injection

Proper placement of the needle or catheter in the epidural space should be verified before sufentanil is injected to assure that unintentional intravascular or intrathecal administration does not occur. Unintentional intravascular injection of sufentanil could 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 could produce effects of high spinal anesthesia including prolonged paralysis and delayed recovery. If analgesia is inadequate, the placement and integrity of the catheter should be verified prior to the administration of any additional epidural medications. Sufentanil should be administered epidurally by slow injection.

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

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), Sufentanil Citrate Injection may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of increasing intracranial pressure.

Risks of Use in Patients with Gastrointestinal Conditions

Sufentanil may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders

Sufentanil may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during Sufentanil Citrate Injection therapy.

Risks of Driving and Operating Machinery

Sufentanil Citrate Injection may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery after Sufentanil Citrate Injection administration.

Overdosage

Clinical Presentation

Acute overdose with Sufentanil Citrate Injection can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2)].

Treatment of Overdose

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to sufentanil overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to sufentanil overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of sufentanil in Sufentanil Citrate Injection, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product's prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

Sufentanil Citrate Description

Sufentanil Citrate Injection, is an opioid agonist, available as a solution containing 50 mcg/mL eq. of sufentanil base, adjusted to pH 3.5 to 6.0. The chemical name is N-[4-(methyoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide: 2-hydroxy-1,2,3-propanetricarboxylate (1:1). The molecular weight is 578.68. It has the following chemical structure.

Sufentanil Citrate Injection, is a sterile, non-pyrogenic, preservative free aqueous solution for intravenous or epidural injection.

How Supplied/Storage and Handling

Sufentanil Citrate Injection, USP is a sterile aqueous, preservative-free solution, containing 50 mcg/mL eq. of sufentanil base, for intravenous and epidural use, supplied as:

NDC 17478-050-01	1 mL ampules in packages of 10
NDC 17478-050-02	2 mL ampules in packages of 10
NDC 17478-050-05	5 mL ampules in packages of 10

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light.

U.S. Patent No. 3,998,834
MAY 1995, SEPTEMBER 1995

AKORN
Manufactured by: Akorn, Inc.
Lake Forest, IL 60045

SFA0N Rev. 12/16

Principal Display Panel Text for Container Label:

NDC 17478-050-01 1 mL Ampule

Sufentanil Citrate CII

Injection, USP

50 mcg/mL

Sufentanil base Rx only

FOR INTRAVENOUS

AND EPIDURAL USE

Preservative Free

Principal Display Panel Text for Carton Label:

NDC 17478-050-01 10 Ampules (1 mL each)