Sufenta

Pregnancy

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage

Labor or delivery

• Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

Lactation

The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped; naloxone may precipitate opioid withdrawal in a breast-fed infant whose mother received opioid analgesics

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

• Taylor Pharmaceuticals

Your doctor will check your progress closely while you or your child are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.

Symptoms of an overdose include extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, and cold, clammy skin. Call your doctor right away if you or your child notice these symptoms.

Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with sufentanil may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

This medicine may make you dizzy, drowsy, or lightheaded. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. Sit or lie down if you feel dizzy. Stand up carefully.

Tell your doctor if you or your child have stiffness in the muscles of your neck, chest, hands, or legs after receiving this medicine.

Check with your doctor right away if you or your child have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

Using this medicine while you are pregnant may cause neonatal withdrawal syndrome in your newborn baby. Tell your doctor right away if your baby has an abnormal sleep pattern, diarrhea, a high-pitched cry, irritability, shakiness or tremors, weight loss, vomiting, or fails to gain weight.

Using too much of this medicine may cause infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Pharmacology

Sufenta is an opioid analgesic. When used in balanced general anesthesia, Sufenta has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, Sufenta is approximately 5 to 7 times as potent as fentanyl.

Assays of histamine in patients administered Sufenta have shown no elevation in plasma histamine levels and no indication of histamine release.

(See dosage chart for more complete information on the intravenous use of Sufenta.)

Pharmacodynamics

At intravenous doses of up to 8 mcg/kg, Sufenta is an analgesic component of general anesthesia; at intravenous doses ≥8 mcg/kg, Sufenta produces a deep level of anesthesia. Sufenta produces a dose related attenuation of catecholamine release, particularly norepinephrine.

At intravenous dosages of ≥8 mcg/kg, Sufenta produces hypnosis and anesthesia without the use of additional anesthetic agents. A deep level of anesthesia is maintained at these dosages, as demonstrated by EEG patterns. Dosages of up to 25 mcg/kg attenuate the sympathetic response to surgical stress. The catecholamine response, particularly norepinephrine, is further attenuated at doses of Sufenta of 25 to 30 mcg/kg, with hemodynamic stability and preservation of favorable myocardial oxygen balance.

Sufenta has an immediate onset of action, with relatively limited accumulation. Rapid elimination from tissue storage sites allows for relatively more rapid recovery as compared with equipotent dosages of fentanyl. At dosages of 1 to 2 mcg/kg, recovery times are comparable to those observed with fentanyl; at dosages of >2 to 6 mcg/kg, recovery times are comparable to enflurane, isoflurane and fentanyl. Within the anesthetic dosage range of 8 to 30 mcg/kg of Sufenta, recovery times are more rapid compared to equipotent fentanyl dosages.

The vagolytic effects of pancuronium may produce a dose dependent elevation in heart rate during Sufenta-oxygen anesthesia. The use of moderate doses of pancuronium or of a less vagolytic neuromuscular blocking agent may be used to maintain a stable lower heart rate and blood pressure during Sufenta-oxygen anesthesia. The vagolytic effects of pancuronium may be reduced in patients administered nitrous oxide with Sufenta.

Preliminary data suggest that in patients administered high doses of Sufenta, initial dosage requirements for neuromuscular blocking agents are generally lower as compared to patients given fentanyl or halothane, and comparable to patients given enflurane.

Bradycardia is infrequently seen in patients administered Sufenta-oxygen anesthesia. The use of nitrous oxide with high doses of Sufenta may decrease mean arterial pressure, heart rate and cardiac output.

Sufenta at 20 mcg/kg has been shown to provide more adequate reduction in intracranial volume than equivalent doses of fentanyl, based upon requirements for furosemide and anesthesia supplementation in one study of patients undergoing craniotomy. During carotid endarterectomy, Sufenta-nitrous oxide/oxygen produced reductions in cerebral blood flow comparable to those of enflurane-nitrous oxide/oxygen. During cardiovascular surgery, Sufenta-oxygen produced EEG patterns similar to fentanyl-oxygen; these EEG changes were judged to be compatible with adequate general anesthesia.

The intraoperative use of Sufenta at anesthetic dosages maintains cardiac output, with a slight reduction in systemic vascular resistance during the initial postoperative period. The incidence of postoperative hypertension, need for vasoactive agents and requirements for postoperative analgesics are generally reduced in patients administered moderate or high doses of Sufenta as compared to patients given inhalation agents.

Skeletal muscle rigidity is related to the dose and speed of administration of Sufenta. This muscular rigidity may occur unless preventative measures are taken (see WARNINGS).

Decreased respiratory drive and increased airway resistance occur with Sufenta. The duration and degree of respiratory depression are dose related when Sufenta is used at sub-anesthetic dosages. At high doses, a pronounced decrease in pulmonary exchange and apnea may be produced.

Onset of analgesic effect occurs within approximately 10 minutes of administration of epidural doses of Sufenta and bupivacaine. Duration of analgesia following a single epidural injection of 10 to 15 mcg Sufenta and bupivacaine 0.125% averaged 1.7 hours.

During labor and vaginal delivery, the addition of 10 to 15 mcg Sufenta to 10 mL 0.125% bupivacaine provides an increase in the duration of analgesia compared to bupivacaine without an opioid. Analgesia from 15 mcg Sufenta plus 10 mL 0.125% bupivacaine is comparable to analgesia from 10 mL of 0.25% bupivacaine alone. Apgar scores of neonates following epidural administration of both drugs to women in labor were comparable to neonates whose mothers received bupivacaine without an opioid epidurally.

Pharmacokinetics

The pharmacokinetics of intravenous Sufenta can be described as a three-compartment model, with a distribution time of 1.4 minutes, redistribution of 17.1 minutes and elimination half-life of 164 minutes in adults. The elimination half-life of Sufenta is shorter (e.g. 97 +/- 42 minutes) in infants and children, and longer in neonates (e.g. 434 +/- 160 minutes) compared to that of adolescents and adults. The liver and small intestine are the major sites of biotransformation. Approximately 80% of the administered dose is excreted within 24 hours and only 2% of the dose is eliminated as unchanged drug. Plasma protein binding of Sufentanil, related to the alpha acid glycoprotein concentration, was approximately 93% in healthy males, 91% in mothers and 79% in neonates.

After epidural administration of incremental doses totaling 5 to 40 mcg Sufenta during labor and delivery, maternal and neonatal Sufentanil plasma concentrations were at or near the 0.05 to 0.1 ng/mL limit of detection, and were slightly higher in mothers than in their infants.

Epidural use in Labor and Delivery

Epidural Sufentanil was tested in 340 patients in two (one single-center and one multicenter) double-blind, parallel studies. Doses ranged from 10 to 15 mcg Sufentanil and were delivered in a 10 mL volume of 0.125% bupivacaine with and without epinephrine 1:200,000. In all cases Sufentanil was administered following a dose of local anesthetic to test proper catheter placement. Since epidural opioids and local anesthetics potentiate each other, these results may not reflect the dose or efficacy of epidural Sufentanil by itself.

Individual doses of 10 to 15 mcg Sufenta plus bupivacaine 0.125% with epinephrine provided analgesia during the first stage of labor with a duration of 1 to 2 hours. Onset was rapid (within 10 minutes). Subsequent doses (equal dose) tended to have shorter duration. Analgesia was profound (complete pain relief) in 80% to 100% of patients and a 25% incidence of pruritus was observed. The duration of initial doses of Sufenta plus bupivacaine with epinephrine is approximately 95 minutes, and of subsequent doses, 70 minutes.

There are insufficient data to critically evaluate neonatal neuromuscular and adaptive capacity following recommended doses of maternally administered epidural Sufentanil with bupivacaine. However, if larger than recommended doses are used for combined local and systemic analgesia, e.g. after administration of a single dose of 50 mcg epidural Sufentanil during delivery, then impaired neonatal adaption to sound and light can be detected for 1 to 4 hours and if a dose of 80 mcg is used impaired neuromuscular coordination can be detected for more than 4 hours.

Sufenta (Sufentanil citrate) is indicated for intravenous administration in adults and pediatric patients:

as an analgesic adjunct in the maintenance of balanced general anesthesia in patients who are intubated and ventilated.

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.

Sufenta (Sufentanil citrate) is indicated for epidural administration as an analgesic combined with low dose bupivacaine, usually 12.5 mg per administration, during labor and vaginal delivery.

SEE DOSAGE AND ADMINISTRATION SECTION FOR MORE COMPLETE INFORMATION ON THE USE OF Sufenta.

The most common adverse reactions of opioids are respiratory depression and skeletal muscle rigidity, particularly of the truncal muscles. Sufenta may produce muscular rigidity that involves the skeletal muscles of the neck and extremities. See CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS on the management of respiratory depression and skeletal muscle rigidity. Urinary retention has been associated with the use of epidural opioids but was not reported in the clinical trials of epidurally administered Sufentanil due to the use of indwelling catheters. The incidence of urinary retention in patients without urinary catheters receiving epidural Sufentanil is unknown; return of normal bladder activity may be delayed.

The following adverse reaction information is derived from controlled clinical trials in 320 patients who received intravenous Sufentanil during surgical anesthesia and in 340 patients who received epidural Sufentanil plus bupivacaine 0.125% for analgesia during labor and is presented below. Based on the observed frequency, none of the reactions occurring with an incidence less than 1% were observed during clinical trials of epidural Sufentanil used during labor and delivery (N=340).

In general cardiovascular and musculoskeletal adverse experiences were not observed in clinical trials of epidural Sufentanil. Hypotension was observed 7 times more frequently in intravenous trials than in epidural trials. The incidence of central nervous system, dermatological and gastrointestinal adverse experiences was approximately 4 to 25 times higher in studies of epidural use in labor and delivery.

Probably Causally Related: Incidence Greater than 1% - Derived from clinical trials (See preceding paragraph)

Cardiovascular: bradycardia1, hypertension1, hypotension1.

Musculoskeletal: chest wall rigidity1.

Central Nervous System: somnolence1.

Dermatological: pruritus (25%).

Gastrointestinal: nausea1, vomiting1.

Probably Causally Related: Incidence Less than 1% - Derived from clinical trials (Adverse events reported in post-marketing surveillance, not seen in clinical trials, are italicized.)

Body as a whole: anaphylaxis.

Cardiovascular: arrhythmia2, tachycardia2, cardiac arrest.

Central Nervous System: chills2.

Dermatological: erythema2.

Musculoskeletal: skeletal muscle rigidity of neck and extremities.

Respiratory: apnea2, bronchospasm2, postoperative respiratory depression2.

Miscellaneous: intraoperative muscle movement2.

Applies to sufentanil: injection solution

Along with its needed effects, sufentanil (the active ingredient contained in Sufenta) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking sufentanil:

• Agitation
• blurred vision
• confusion
• cough
• darkening of the skin
• diarrhea
• difficult or troubled breathing
• difficulty with swallowing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast heartbeat
• fever
• hives, itching, or skin rash
• irregular, fast or slow, or shallow breathing
• loss of appetite
• mental depression
• muscle stiffness
• nausea
• overactive reflexes
• pale or blue lips, fingernails, or skin
• poor coordination
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• restlessness
• shivering
• sweating
• talking or acting with excitement you cannot control
• tightness in the chest
• trembling or shaking
• twitching
• unusual tiredness or weakness
• vomiting

Applies to sufentanil: compounding powder, injectable solution

General

The most commonly reported adverse events have been apnea, rigidity, and bradycardia.[Ref]

Respiratory

Common (1% to 10%): Respiratory depression
Uncommon (0.1% to 1%): Apnea
Frequency not reported: Respiratory arrest[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity
Postmarketing reports: Anaphylaxis[Ref]

Cardiovascular

Common (1% to 10%): Increased heart rate, increased blood pressure, decreased blood pressure
Uncommon (0.1% to 1%): Decreased heart rate
Rare (0.01% to 0.1%): Bradycardia
Frequency not reported: Severe bradycardia, severe hypotension including orthostatic hypotension, syncope[Ref]

Musculoskeletal

Common (1% to 10%): Involuntary muscle spasms, muscle twitching
Frequency not reported: Muscle rigidity, muscle movement[Ref]

Gastrointestinal

Very common (10% or more): Nausea, vomiting
Common (1% to 10%): Constipation, dyspepsia
Uncommon (0.1% to 1%): Dry mouth

Opioids:
Frequency not reported: increase in serum amylase[Ref]

Psychiatric

Common (1% to 10%): Confusional state
Uncommon (0.1% to 1%): Apathy, nervousness
Frequency not reported: Addiction, abuse, misuse[Ref]

Nervous system

Cases of serotonin syndrome have been reported during concomitant use of opioids with serotonergic drugs.[Ref]

Common (1% to 10%): Dizziness, headache, sedation
Uncommon (0.1% to 1%): Somnolence, paresthesia, ataxia, dystonia, hyperreflexia
Frequency not reported: Seizures, coma

Opioids:
Postmarketing reports: Serotonin syndrome[Ref]

Dermatologic

Very common (10% or more): Pruritus (up to 25%)
Uncommon (0.1% to 1%): Hyperhidrosis, rash, dry skin
Frequency not reported: Erythema[Ref]

Genitourinary

Common (1% to 10%): Urinary retention[Ref]

Ocular

Uncommon (0.1% to 1%): Vision disturbances
Frequency not reported: Miosis[Ref]

Other

Very common (10% or more): Pyrexia
Uncommon (0.1% to 1%): Chills, asthenia
Frequency not reported: Drug withdrawal syndrome[Ref]

Endocrine

Cases of adrenal insufficiency have been reported with opioid use of greater than 1-month duration. Cases of androgen deficiency have occurred with chronic opioid use.[Ref]

Opioids:
Postmarketing reports: Adrenal insufficiency, androgen deficiency[Ref]

Some side effects of Sufenta may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

LactMed Record Number

386

Last Revision Date

20170905

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.