Sufenta

Generic Name: Sufentanil Citrate
Class: Opiate Agonists
VA Class: CN101
Chemical Name: N - [4 - (Methoxymethyl) - 1 - [2 - (2 - thieyl)ethyl] - 4 - piperidinyl] - N - phenylpropanamide2 - hydroxy - 1,2,3 - propanetricarboxylate (1:1)
Molecular Formula: C22H30N2O2S•O6H8O7
CAS Number: 60561-17-3

Introduction

Opiate agonist; synthetic phenylpiperidine derivative.1 3 4 5

Uses for Sufenta

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

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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

Sufenta Dosage and Administration

General

Premedication

  • Selection of preanesthetic medication(s) should be based on the individual needs of the patient.1

Administration

Administer by IV injection, intermittent or continuous IV infusion, or epidural injection.1 4 7 8 10 11 12 13 19

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administration of small volumes may require use of a tuberculin syringe or equivalent.1

Rate of Administration

Administer by slow injection or intermittent or continuous infusion; individualize rate based on patient’s needs.1

Concomitant Administration of a Neuromuscular Blocking Agent

Risk of muscular rigidity (particularly of the truncal muscles) is related to the dose and rate of the infusion; however, administration of a neuromuscular blocking agent prior to sufentanil therapy can reduce the risk.1

The neuromuscular blocking agent used should be compatible with the patient’s condition, taking into account the hemodynamic effects of the drug, the cardiovascular status of the patient, existing drug therapy (e.g., preoperative use of β-adrenergic blocking agents), and the degree of skeletal muscle relaxation required.1

Administration of a Neuromuscular Blocking Agent with Sufentanil1

Sufentanil Dosage

Neuromuscular Blocking Agent Dosage

<8 mcg/kg

Administer up to 25% of the full paralyzing dose just prior to sufentanil1

>8 mcg/kg (titrated by slow IV infusion)

Administer a full paralyzing dose following loss of consciousness (e.g., loss of eyelash reflex, loss of response to voice command)1 61

>8 mcg/kg (rapidly administered anesthetic doses)

Administer a full paralyzing dose simultaneously with sufentanil1 or immediately after loss of consciousness61

Epidural Administration

For drug compatibility information, see Compatibility under Stability.

Specialized techniques are required for epidural administration; administration should be performed only by qualified individuals familiar with the techniques of administration, dosages, and special patient management problems associated with epidural administration.1

Dosage

Available as sufentanil citrate; dosage expressed in terms of sufentanil.1

Adjust dosage carefully according to body weight, individual requirements and response, physical status and underlying pathologic condition, premedication or concomitant medication(s), the anesthetic(s) being used, and the nature and duration of the surgery.1

Administer additional doses when patient movement and/or changes in vital signs indicate surgical stress or lightening of analgesia, and adjust according to individual requirements, response, and the anticipated remaining duration of the surgical procedure.1

Pediatric Patients

Anesthesia
General Anesthesia (as sole anesthetic agent) for Cardiovascular Surgery
IV

Children <12 years of age: Initially, 10–25 mcg/kg in conjunction with 100% oxygen and a skeletal muscle relaxant.1 8 61 Additional doses of up to 25–50 mcg each (or, alternatively, 1–2 mcg/kg each)61 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.1

Neonates: Reduce dosage, especially in those with cardiovascular disease, according to the decrease in clearance.89 (See Pediatric Use under Cautions.)

Adults

Anesthesia
Analgesic Component of 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.1 88 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.1 88

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.1 88 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.1 88

General Anesthesia (as sole anesthetic agent)
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.1 88 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).1 88 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.1 88

Pain
Obstetric Analgesia
Epidural

10–15 mcg (in combination with 10 mL of bupivacaine 0.125% with or without epinephrine).1 88 Doses may be repeated twice (for a total of 3 doses) at ≥1-hour intervals until delivery.1 88

Prescribing Limits

Adults

Anesthesia
Analgesic Component of General Anesthesia
IV

Minor or major surgical procedures: Total dose of ≤1 mcg/kg per hour of expected surgical time.1

General Anesthesia (as sole anesthetic agent)
IV

Total dose for procedure: ≤ 30 mcg/kg.1

Special Populations

Hepatic Impairment

Adjust dosage carefully; elimination of the drug may be decreased.1 60

Renal Impairment

Adjust dosage carefully; elimination of the drug may be decreased.1 60

Geriatric and Debilitated Patients

Reduce initial dosage;1 adjust additional doses according to the initial response and desired effect.1 61

Obese Patients

Base dosage on an estimate of ideal (lean) body weight if body weight exceeds ideal weight by >20%.1

Cautions for Sufenta

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.)

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

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

Interactions for Sufenta

Specific Drugs

Drug

Interaction

Comments

β-Adrenergic blocking agents

Possible increased incidence and degree of bradycardia and hypotension during sufentanil induction in patients receiving chronic β-blocker therapy1

Patients with CAD receiving chronic preoperative β-blocker therapy appear to require lower initial and fewer supplemental doses of sufentanil during CABG surgery than do patients who have not received preoperative β-blocker therapy10

Calcium-channel blocking agents

Increased incidence and degree of bradycardia and hypotension during sufentanil induction in patients receiving chronic calcium-channel blocker therapy1

CNS depressants (e.g., opiate agonists, general anesthetics, tranquilizers, sedatives, hypnotics)

Potentiation of CNS and cardiovascular effects1

Use with caution; reduce dosage of at least one of the drugs when used concomitantly1

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 sufentanil1

Neuromuscular blocking agents

Possible tachycardia following administration of high doses of pancuronium during anesthesia with sufentanil and oxygen;1 4 38 hypertension and an increase in cardiac index may occur4

Bradycardia and hypotension reported during anesthesia during concomitant administration of neuromuscular blocking agents with sufentanil and oxygen; effects may be increased in patients also receiving calcium-channel blockers or β-blockers;1 bradycardia reported rarely following concomitant administration of sufentanil with succinylcholine1

To maintain a stable, lower HR and BP during anesthesia, use moderate doses of pancuronium or use a neuromuscular blocking agent with a lesser inhibitory effect on the vagus nerve 1

Sufenta 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.4 10 13 15 16 18

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.1 88

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.20 Following administration of anesthetic doses (about 13–19 mcg/kg total), patient response to verbal command4 13 15 and adequate ventilation4 15 occurs at 0.6–1.8 and 5.6 hours, respectively.

Following IM administration of single doses of 0.15, 0.3, or 0.5 mcg/kg in patients with pain, the approximate duration of detectable analgesia was 2.3, 3.7, and 3.8 hours, respectively.21

Following epidural administration of 10–15 mcg and 0.125% bupivacaine with epinephrine 1:200,000 during the first stage of labor, the duration of action was 1–2 hours.1 88

Distribution

Extent

Distribution into human body tissues and fluids has not been fully characterized;14 however, the drug is highly lipophilic and is rapidly and extensively distributed in animals.4

Not known whether sufentanil crosses the placenta2 or distributes into milk.1 2

Plasma Protein Binding

Approximately 93% bound at plasma pH 7.41 4 6 14 (mainly to albumin; α-, α1-, β-, and γ-globulins; and α1-acid glycoprotein).6 14

Because a large portion of the drug appears to be bound to α1-acid glycoprotein, binding may be affected by disease states in which this protein is altered.4 6 14 24

Binding in plasma is independent of plasma drug concentration within the therapeutic range (i.e., 0.1–10 ng/mL);4 6 however, binding is affected by changes in plasma pH.4 6 14 Increases in plasma pH from 7.4 to 7.8 increase sufentanil binding by about 30%; decreases in plasma pH from 7.4 to 7 decrease binding by about 30%.6

Elimination

Metabolism

Appears to be metabolized mainly in the liver and small intestine1 2 via N-dealkylation and O-demethylation.4

The O-demethylated metabolite appears to have about 10% of the analgesic activity of the unchanged drug.4

Elimination Route

Excreted principally in urine and also in feces via biliary elimination;1 2 60 only 2% of a dose is excreted unchanged in urine and feces.1 2

Half-life

Triphasic; plasma concentrations decline rapidly secondary to redistribution.1 2 4 5 14 22

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.1 2 4 5 14 22 23

Elimination half-life is longer (434 minutes) in neonates but shorter in infants and children (97 minutes), compared with adults and adolescents.89

Stability

Storage

Parenteral

Injection

15–25°C; protect from light.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Sufentanil citrate is hydrolyzed in acidic solutions.60

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Variable

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Bupivacaine HCl

Ropivacaine HCl

Ziconotide acetate

Y-Site CompatibilityHID

Compatible

Amphotericin B cholesteryl sulfate complex

Bivalirudin

Cefepime HCl

Ceftazidime

Cisatracurium besylate

Dexmedetomidine HCl

Etomidate

Fenoldopam mesylate

Hetastarch in lactated electrolyte injection (Hextend)

Linezolid

Palonosetron HCl

Propofol

Remifentanil HCl

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

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.1

* 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

50 mcg (of sufentanil) per mL*

Sufenta (C-II)

Akorn

Sufentanil Citrate Injection (C-II)

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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6. Meuldermans WEG, Hurkmans RMA, Heykants JJP. Plasma protein binding and distribution of fentanyl, sufentanil, alfentanil and lofentanil in blood. Arch Int Pharmacodyn Ther. 1982; 257:4-19. [PubMed 6214227]

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50. de Castro J, Van de Water A, Wouters L et al. Comparative study of cardiovascular, neurological and metabolic side-effects of eight narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R39 209, sufentanil, R34 995. I. Comparative study on the acute toxicity and hemodynamic effects of the narcotics in high and massive doses in curarised and mechanically ventilated dogs. Acta Anaesthesiol Belg. 1979; 30:5-54. [PubMed 382728]

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53. Flacke JW, Van Etten A, Flacke WE. Greatest histamine release from meperidine among four narcotics: double-blind study in man. Anesthesiology. 1983; 59:A51.

54. Flacke WE, Van Etten AP, Flacke JW et al. Plasma histamine levels during sufentanil anesthesia for coronary bypass graft surgery. Anesth Analg. 1983; 62:260-1.

55. Bovill JG, Sebel PS, Fiolet JWT et al. The influence of sufentanil on endocrine and metabolic responses to cardiac surgery. Anesth Analg. 1983; 62:391-7. [IDIS 168279] [PubMed 6219596]

56. Young ML, Smith DS, Greenberg J et al. Effects of sufentanil on regional cerebral glucose metabolism in rats. Anesthesiology. 1983; 59:A335.

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