Dsuvia (Sufentanil) is a very potent opioid pain medicine that is 500 times more potent than morphine is used in the management of severe pain not responding to other non-opioid pain medicines.

Sufentanil (Dsuvia) Uses:

• Acute pain management (sublingual tablet):

  • Management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are not enough.

• Limitations of use:

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

• Epidural analgesia (injection):

  • For epidural administration for analgesia combined with low dose bupivacaine during labor and vaginal delivery.

• Surgical analgesia (injection):

  • Analgesic adjunct for the maintenance of balanced general anesthesia in patients who are intubated and ventilated.

• Surgical anesthesia (injection):

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

Sufentanil (Dsuvia) Dose in Adults

Sufentanil (Dsuvia) Dose in Acute pain management:

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

Note:

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

Sufentanil (Dsuvia) Dose in Surgical analgesia (as a component of balanced anesthesia) when the surgery is expected to last: 1 to 2 hours:

• IV: Total dose: 1 to 2 mcg/kg with N2 O/O2;
• ≥75% of total dose may be administered by slow injection or infusion prior to intubation (titrate to the individual response)

• Maintenance:

  • Incremental dosing:

    • According to the drug manufacturer, 10 to 25 mcg may be administered as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.
    • May also administer doses in the range of 5 to 20 mcg as required or at 0.1 to 0.25 mcg/kg as needed.
    • The total dose should not exceed 1 mcg/kg/hour of expected surgical time.

  • Continuous infusion:

    • May also be administered in continuous infusion with the infusion rate based on the induction dose used.
    • Maximum infusion rate according to the manufacturer: at 1 mcg/kg/hour.
    • May also administer doses in the range at 0.3 to 0.9 mcg/kg/hour or at 0.5 to 1.5 mcg/kg/hour.

Sufentanil (Dsuvia) Dose in Surgical analgesia (as a component of balanced anesthesia) when the surgery is expected to last 2 to 8 hours:

• Total dose: at 2 to 8 mcg/kg with N O/O ;
• ≤75% of total dose may be administered by slow intravenous injection or infusion prior to intubation (titrate to individual response).

• Maintenance:

  • Incremental dosing:

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

  • Continuous infusion:

    • May also be administered in continuous intravenous infusion with the infusion rate based on the induction dose used.
    • Maximum infusion rate according to the manufacturer: at 1 mcg/kg/hour.
    • May also administer doses in the range at 0.3 to 0.9 mcg/kg/hour or at 0.5 to 1.5 mcg/kg/hour.

Sufentanil Dose in the treatment of Surgical anesthesia:

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

• Maintenance:

  • Incremental dosing: at 5 to 10 mcg/kg as needed in anticipation of surgical stress
  • Continuous infusion: Base infusion rate on the induction dose so that the total dose for the procedure does not exceed at 30 mcg/kg

Sufentanil (Dsuvia) Dose in Analgesia for labor and delivery:

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

Sufentanil (Dsuvia) Dose in Childrens

Note: 

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

Sufentanil (Dsuvia) Dose in Cardiac surgery anesthesia:

IV:

• Initial: 5 to 25 mcg/kg;
• repeat the maintenance doses:
  • 1 to 5 mcg/kg/doses up to 25 to 50 mcg/dose as needed based on response to the initial dose and as determined by changes in vital signs indicating surgical stress or lightening of anesthesia;
  • data based on experience in cardiac surgery, which requires much higher induction and maintenance doses;
  • lower dosing may be enough for other procedures.

Dsuvia (Sufentanil) dose in the treatment of Epidural anesthesia:

• Infants ≥3 months and Children:

  • Epidural injection: Initial bolus: at 0.2 mcg/kg followed by continuous infusion at 0.1 mcg/kg/hour in combination with ropivacaine.

Dsuvia (Sufentanil) Dose for procedural and preoperative sedation: 

• Children ≥3 years:

  • Intranasal: at 1 to 3 mcg/kg in combination with other agents.

Pregnancy Risk Category: C

• Neonatal withdrawal syndrome can be caused by prolonged maternal opioid use during pregnancy. If not treated and recognized promptly, it could prove to be fatal.
• Pregnant women who require prolonged opioid therapy should be notified and ensure that the treatment is available.
• Opioids can cross the placenta. Opioids can cross the placenta and cause birth defects, preterm births, low fetal growth, stillbirth, or other complications.
• A pregnant woman may experience withdrawal symptoms if they are exposed to chronic opioids.
• Neonatal abstinence Syndrome (NAS) Symptoms of opioid exposure can be autonomic, gastrointestinal, or neurologic.
• Opioid-dependent mothers may give birth to babies who are also opioid dependent.
• Opioids can cause respiratory depression in neonates and psycho-physiologic side effects in newborns. Mothers who have given opioids to their babies during labor must be monitored.
• Sufentanil should not be used during labor or right before it.
• In labor and delivery, epidural sufentanil is administered with or without epinephrine. Pregnant women should not use intravenous epidurals or higher doses.
• Opioids may temporarily alter the heart rate of the foetus when used to relieve pain during labor.
• Long-term opioid abuse may result in lower fertility for males and women.

Sufentanil use during breastfeeding:

• It is unknown if breast milk contains sufentanil.
• According to the drug manufacturer the decision to discontinue or continue breastfeeding while on therapy should consider the risks to infants, the benefits to the mother, and the benefits to the mother.
• The natural instinct to breastfeed in the first hours after birth may be affected by maternal opioids.
• Women who are breastfeeding should consider a short-acting opioid like sufentanil.
• Monitor infants breastfeeding opioid-exposed infants (Montgomery 2012).

Dsuvia dose in Kidney Disease:

• There are no dosage adjustments provided in the drug manufacturer’s labeling.
• Use with caution and reduce the dose as needed;
• titrate slowly and closely monitor for signs of CNS and respiratory depression.

Dsuvia Dose in Liver disease:

• There are no dosage adjustments provided in the drug manufacturer’s labeling.
• Use with caution and reduce the dose as needed;
• titrate slowly and closely monitor for signs of CNS and respiratory depression.

Common Side Effects of Sufentanil (Dsuvia):

• Central nervous system:

  • Headache

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Nausea

Less Common Side Effects of Sufentanil (Dsuvia):

• Cardiovascular:

  • Hypotension

• Central nervous system:

  • Dizziness

• Gastrointestinal:

  • Vomiting

Rare side effects of Dsuvia (Sufentanil):

• Cardiovascular:

  • Bradycardia
  • ECG Abnormality
  • Flushing
  • Hypertension
  • Orthostatic Hypotension
  • Oxygen Saturation Decreased
  • Peripheral Vasodilation
  • Presyncope
  • Sinus Tachycardia
  • Syncope

• Central Nervous System:

  • Agitation
  • Anxiety
  • Confusion
  • Disorientation
  • Drowsiness
  • Drug Abuse
  • Drug Dependence
  • Euphoria
  • Hallucination
  • Insomnia
  • Lethargy
  • Memory Impairment
  • Mental Status Changes
  • Sedation

• Dermatologic:

  • Hyperhidrosis
  • Skin Rash

• Gastrointestinal:

  • Abdominal Distension
  • Abdominal Distress
  • Constipation
  • Decreased Gastrointestinal Motility
  • Diarrhea
  • Dyspepsia
  • Eructation
  • Flatulence
  • Gastritis
  • Hiccups
  • Intestinal Obstruction (Postoperative)
  • Oral Hypoesthesia
  • Retching
  • Upper Abdominal Pain
  • Xerostomia

• Genitourinary:

  • Decreased Urine Output
  • Oliguria
  • Urinary Hesitancy
  • Urinary Retention

• Hepatic:

  • Increased Liver Enzymes
  • Increased Serum Aspartate Aminotransferase

• Neuromuscular & Skeletal:

  • Muscle Rigidity
  • Muscle Spasm

• Ophthalmic:

  • Miosis

• Renal:

  • Renal Failure Syndrome

• Respiratory:

  • Apnea
  • Atelectasis
  • Bradypnea
  • Hypoventilation
  • Hypoxia
  • Respiratory Depression
  • Respiratory Distress
  • Respiratory Failure

Contraindications to Dsuvia (Sufentanil):

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

Sublingual tablets may also be contraindicated

• Respiratory depression is a serious problem
• Acute or severe bronchial asthma in unmonitored settings or without resuscitative devices;
• Paralytic ileus, suspected or known gastrointestinal obstruction

Canadian labeling: Additional contraindications not listed in the US labeling:

• Hypersensitivity to fentanyl and other morphinomimetics
• IV use during labor, or before clamping cord during Cesarean section
• Patients with severe hemorhage, shock, septicemia or infection at the puncture site may require epidural administration

There is not much evidence of cross-reactivity between opioids and allergenic substances.

Cross-sensitivity can be possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Adrenocortical Insufficiency

  • Patients with adrenal insufficiency (Addison disease) should be cautious.
  • Long-term opioid abuse can lead to secondary hypogonadism. This could cause infertility, sexual dysfunction, mood disorders, and osteoporosis.

• Bradyarrhythmias:

  • Bradycardia can be severe; patients with bradyarrhythmias should be cautious.

• CNS depression:

  • CNS depression can lead to mental or physical impairments.
  • Patients should be advised about tasks that require mental alertness, such as driving or operating machinery.

• Hypotension

  • Can cause severe hypotension (including orthostatic hypertension and syncope).
  • Patients with hypovolemia, heart disease (including acute MI), and drugs that can exaggerate hypotensive effects (such as phenothiazines and general anesthetics) should be cautious.
  • After dose titration or initiation, monitor for hypotension symptoms.
  • Patients with circulatory shock should be cautious about injecting.
  • Patients with circulatory shock should not take sublingual tablets.

• Respiratory depression [US Boxed Warning]

  • Sufentanil can cause severe, life-threatening or fatal respiratory depression.
  • Monitor for signs of respiratory depression, especially when sufentanil is being administered or the dose is being increased.
  • The sedating effects that opioids can cause by carbon dioxide retention may be exacerbated by opioid-induced respiratory depression.

• Serotonin syndrome:

  • Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of sufentanil and serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs, 5-HT receptor antagonists, mirtazapine, trazodone, tramadol) and agents that impair metabolism of serotonin (eg, MAO inhibitors).
  • Pay attention to signs of SS in patients.
    • Mental status changes (eg: agitation, hallucinations and delirium, coma).
    • autonomic instability (eg tachycardia or labile blood pressure, diaphoresis)
    • neuromuscular changes (eg, tremor, rigidity, myoclonus);
    • GI symptoms (eg, nausea, vomiting, diarrhea); and/or
    • seizures.
  • Sufentanil should be discontinued if serotonin symptoms are suspected.

• Conditions abdominales:

  • Patients with acute abdominal conditions may not be diagnosed or treated appropriately.
  • Sublingual tablets are contraindicated in patients with GI obstruction or paralytic ileus.

• Insufficiency of the biliary tract:

  • Patients with biliary dysfunction (including acute pancreatitis) should be cautious.
  • Opioid may cause constriction in the sphincter Oddi.

• CNS depression and coma

  • Patients with impaired consciousness and coma should be cautious as they are more susceptible to the intracranial effects CO retention.

• Delirium tremens:

  • Patients with delirium-tremens should be cautious when using opioids.

• Head trauma

  • Patients with intracranial injuries, intracranial lesions or elevated intracranial Pressure (ICP) should be used with extreme caution. Exaggerated elevations of ICP could occur.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious and reduced the dosage as necessary.

• Obesity:

  • Patients who are severely obese should be taken with caution
  • Lean body weight is recommended for patients who are >20% above their ideal body weight.

• Prostatic hyperplasia, urinary stricture

  • Patients with prostatic hyperplasia or urinary stricture should be cautious when using opioids.

• Psychosis:

  • Patients with toxic psychosis should be treated with caution.

• Renal impairment

  • Patients with impaired renal function should be cautious and reduced the dosage as necessary.

• Respiratory disease

  • Patients with COPD or cor Pulmonale significant should be monitored for respiratory depression. Preventive and titrating therapy is not recommended for patients with severe COPD.

• Seizures:

  • Patients with seizure disorders past should be cautious.
  • This could increase the risk of or worsen preexisting seizure disorders.

• Thyroid dysfunction:

  • Patients with thyroid dysfunction should be cautious when using opioids.

Sufentanil: Drug Interaction

Monitoring parameters:

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

How to administer Dsuvia (Sufentanil)?

• IV:

  • Intermittent doses can be administered intravenously either as a slow injection, ranging from 2-10 minutes to a full infusion or as a slow injection.
  • Also available as continuous infusions

• Oral: Sublingual tablet:

  • Only administer by a licensed health care provider in a medically supervised setting.
  • Use gloves for administering.
  • The tablet is packed in a single-dose container; keep it closed until you are ready to administer.
  • The patient should open his mouth and touch the roof of their mouth with their tongue.
  • Use the single-dose applicator to administer into sublingual space.
  • The patient must not chew or swallow the tablet.
  • Do not eat or drink for at least 10 min after administering the medication.

Mechanism of action of Dsuvia (Sufentanil):

• The CNS binds to opioid receptors.
• After receptor binding has occurred, the effects of opening K+ channels or inhibiting Ca++ channel are felt.
• These mechanisms increase pain threshold and alter pain perception, inhibit ascending painful pathways; short-acting opioid; dose-related inhibition catecholamine release (upto 30 mcg/kg); controls sympathetic response to surgical stress

The onset of action:

• Analgesia:
  • IV: in 1 to 3 minutes;
  • Epidural: in 10 minutes;
  • Sublingual tablets: ~30 minutes.

Duration:

• Dose-dependent:
  • Anesthesia adjunct doses: IV: in 5 minutes;
  • Epidural: at 10 to 15 mcg with bupivacaine 0.125%: 1.7 hours;
  • Sublingual tablets: at ~3 hours.

Protein binding:

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

Metabolism:

• Primarily metabolism is hepatic and small intestine via demethylation and dealkylation

Bioavailability:

• Sublingual tablet: ~53%

Half-life elimination (IV):

• Neonates: 7.2 ± 2.7 hours;
• Infants and Children (2 to 8 years): 97 ± 42 minutes;
• Adolescents 10 to 15 years: 76 ± 33 minutes;
• Adults: 164 minutes
• Sublingual tablet: 2.5 ± 0.85 hours (Fisher 2018)

Time to peak:

• Sublingual tablet: 1 hour

Excretion:

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

Clearance:

• Children 2 to 8 years: 30.5 ± 8.8 mL/minute/kg
• Adolescents: 12.8 ± 12 mL/minute/kg
• Adults: 12.7 ± 0.8 mL/minute/kg

International Brands of Sufentanil:

• Dsuvia
• Dzuveo
• Fentafienil
• Sufenta
• Sufenta Forte
• Sufental
• Sufentil
• Zalviso
• Zuftil

Sufentanil Brands Name in Pakistan:

No Brands Available in Pakistan.