Dzuveo (Sufentanil)

What Is Dzuveo and What Is It Used For?

Dzuveo is a sublingual tablet containing sufentanil, a potent synthetic opioid analgesic that belongs to the class of medicines known as opioid anaesthetics. It is used to treat acute, moderate-to-severe pain in adult patients following surgical procedures, and is administered only in medically supervised healthcare settings.

Sufentanil, the active ingredient in Dzuveo, is one of the most potent opioid analgesics available in clinical practice. It was first synthesised in the 1970s and has been used extensively in anaesthesia and intensive care settings for decades. While sufentanil has traditionally been administered intravenously, Dzuveo represents an innovative formulation that delivers the drug sublingually (under the tongue), providing effective pain relief without the need for needles or intravenous lines.

The sublingual route of administration offers several advantages in the postoperative setting. When the tablet dissolves under the tongue, sufentanil is absorbed directly through the highly vascularised sublingual mucosa and enters the systemic circulation rapidly, bypassing first-pass metabolism in the liver. This results in more predictable drug levels compared to oral administration and eliminates the need for vascular access, which can be a significant advantage for patients who may have limited or difficult intravenous access following surgery.

Dzuveo is specifically designed for short-term use in the immediate postoperative period, with treatment duration limited to a maximum of 48 hours. It is intended for use in settings where patients can be closely monitored by healthcare professionals who are experienced in the use of potent opioid analgesics and who have access to resuscitation equipment, including opioid antagonists such as naloxone.

The medication is delivered using a pre-loaded, single-dose applicator that is designed for use by healthcare professionals only. Each applicator contains one small, blue sublingual tablet with 30 micrograms of sufentanil. The healthcare provider places the tablet under the patient's tongue using the applicator, and the tablet dissolves within minutes to provide pain relief.

What Should You Know Before Taking Dzuveo?

Before receiving Dzuveo, you must inform your doctor about all medical conditions, especially breathing problems, head injuries, heart conditions, liver or kidney disease, and any history of substance abuse. Dzuveo is contraindicated in patients with severe respiratory impairment or known allergy to sufentanil.

Contraindications

Dzuveo must not be used in the following situations:

• Allergy to sufentanil or to any of the other ingredients in Dzuveo (mannitol, dicalcium phosphate, hypromellose, croscarmellose sodium, indigo carmine, stearic acid, or magnesium stearate)
• Severe respiratory depression or severe obstructive airway conditions, as sufentanil can further suppress breathing and may be life-threatening in patients with already compromised respiratory function

Warnings and Precautions

Tell your doctor or nurse before treatment if you have any of the following conditions, as special care or monitoring may be required:

• Breathing problems: Asthma, chronic obstructive pulmonary disease (COPD), wheezing, or shortness of breath. Dzuveo can suppress respiratory drive, and your breathing will be closely monitored throughout treatment
• Head injury or brain tumour: Opioids can increase intracranial pressure and may mask neurological deterioration in patients with head injuries
• Heart and circulation problems: Particularly slow heart rate (bradycardia), irregular heartbeat (arrhythmia), low blood volume (hypovolaemia), or low blood pressure (hypotension)
• Liver or kidney problems: Moderate-to-severe hepatic impairment or severe renal impairment, as these organs are involved in metabolising and eliminating the drug
• Abnormally slow bowel movements: Opioids can exacerbate gastrointestinal motility disorders
• Gallbladder or pancreatic disease: Opioids can cause spasm of the sphincter of Oddi
• History of substance abuse: Personal or family history of alcohol, prescription drug, or illicit drug misuse or dependence
• Smoking: This may affect how your body processes the medication
• Mental health conditions: Depression, anxiety, personality disorders, or any psychiatric condition

Opioid Dependence and Addiction

Sufentanil is a potent opioid with the potential for misuse, abuse, and addiction. Repeated use of opioid analgesics can lead to tolerance (needing higher doses for the same effect) and physical dependence. Because Dzuveo is designed for short-term use (maximum 48 hours) in a supervised hospital setting, the risk is lower than with chronic opioid therapy. However, patients with a history of substance abuse should inform their doctor, as they may require closer monitoring.

If you believe you are becoming dependent on Dzuveo, it is important to inform your doctor immediately. Withdrawal symptoms may include restlessness, anxiety, muscle pain, difficulty sleeping, sweating, and yawning.

Sleep-Related Breathing Disorders

Dzuveo can cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low blood oxygen levels during sleep). Symptoms may include breathing pauses during sleep, night-time awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime drowsiness. If you or someone else notices these symptoms, contact your doctor, who may consider dose reduction.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, tell your doctor before receiving Dzuveo. Dzuveo is not recommended during pregnancy or in women of childbearing potential who are not using effective contraception. Animal studies have shown potential risks, and there is insufficient data on use in pregnant women.

Sufentanil passes into breast milk and may cause adverse effects in the nursing infant, including respiratory depression. Breastfeeding is not recommended during treatment with Dzuveo. If you are breastfeeding, discuss alternative pain management options with your doctor.

Children and Adolescents

Dzuveo must not be given to children and adolescents under 18 years of age. Safety and efficacy have not been established in paediatric patients.

Driving and Operating Machinery

Dzuveo significantly impairs the ability to drive and operate machinery because it can cause drowsiness, dizziness, and visual disturbances. You must not drive or operate machinery if you experience any of these symptoms during or after treatment. You should only resume these activities once sufficient time has passed after your last dose of Dzuveo and your doctor has confirmed it is safe to do so.

How Does Dzuveo Interact with Other Drugs?

Dzuveo has significant interactions with several drug classes. Combining it with other central nervous system depressants (benzodiazepines, other opioids, sedatives) greatly increases the risk of life-threatening respiratory depression. MAO inhibitors must not be used within 2 weeks of Dzuveo treatment.

Drug interactions with sufentanil can be dangerous and even life-threatening. It is essential that your medical team knows about every medication you are taking, including prescription drugs, over-the-counter medicines, and herbal supplements. The following interactions are particularly important:

Major Interactions

Moderate Interactions

Alcohol

Do not consume alcohol while receiving Dzuveo. Alcohol is a central nervous system depressant that, when combined with sufentanil, significantly increases the risk of severe respiratory depression, profound sedation, coma, and death. This includes all forms of alcohol, including beer, wine, and spirits. The combined depressant effect on the brainstem respiratory centres can be unpredictable and fatal.

What Is the Correct Dosage of Dzuveo?

Dzuveo is available as a 30 microgram sublingual tablet administered by a healthcare professional using a single-dose applicator. The maximum frequency is one tablet per hour, up to 24 tablets (720 micrograms) per day, for a maximum treatment duration of 48 hours.

Dzuveo is not a medication that patients take on their own. It is administered exclusively by trained healthcare professionals (doctors or nurses) in a medically supervised setting such as a hospital or surgical centre. The dosing is carefully controlled to balance effective pain relief with safety.

Adults

Administration Instructions

The healthcare professional administers Dzuveo as follows:

1. The sealed pouch is opened by tearing along the v-notch at the top. Each pouch contains one clear plastic single-dose applicator with a blue tablet in its tip, plus an oxygen-absorbing packet (which is discarded).
2. The white lock is removed from the green plunger head by squeezing the sides and releasing it. The lock is discarded.
3. The patient is asked to touch their tongue to the roof of their mouth if possible.
4. The applicator tip is placed under the patient's tongue, aimed towards the floor of the mouth. The applicator rests lightly against the teeth or lips.
5. The green plunger is pressed to deposit the tablet under the tongue.
6. The tablet placement is verified, and the used applicator is disposed of according to hospital protocols.

Children

Dzuveo is not approved for use in children and adolescents under 18 years of age. Safety and efficacy have not been established in this population, and it must not be administered to paediatric patients.

Elderly Patients

No specific dose adjustment guidelines exist for elderly patients. However, elderly patients may be more sensitive to opioid effects due to age-related changes in pharmacokinetics and pharmacodynamics. Healthcare providers should exercise caution, consider using longer intervals between doses, and monitor respiratory function closely in older adults.

Patients with Hepatic or Renal Impairment

Patients with moderate-to-severe liver disease or severe kidney disease may metabolise and eliminate sufentanil more slowly, leading to higher and more prolonged drug levels. Dose adjustment or extended monitoring intervals may be necessary. The treating physician will assess the risk-benefit ratio for each individual patient.

Overdose

What Are the Side Effects of Dzuveo?

Like all medicines, Dzuveo can cause side effects. The most common side effects are nausea, vomiting, and feeling warm. The most serious side effect is respiratory depression (slow, shallow breathing), which can be life-threatening. Your medical team will monitor you closely throughout treatment.

Clinical trials and post-marketing surveillance have identified a range of side effects associated with Dzuveo. The frequencies below are based on data from clinical studies and the approved product information. Most side effects are related to the opioid mechanism of action and are dose-dependent.

Effects on Blood Tests

Dzuveo can cause changes in blood test results, including alterations in red blood cell count, white blood cell count, platelet count, and levels of calcium, albumin, potassium, sodium, magnesium, protein, sugar, fats, and phosphate. These changes are typically only detected through laboratory tests. If you need blood tests during or shortly after treatment with Dzuveo, inform the laboratory staff that you are receiving this medication.

Reporting Side Effects

Reporting suspected side effects after a medicine has been authorised is important, as it allows ongoing monitoring of the benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority.

How Should Dzuveo Be Stored?

Dzuveo is stored and handled exclusively by healthcare professionals in hospital settings. It must be kept out of the sight and reach of children, stored in the original packaging to protect from light and oxygen, and not used after the expiry date.

As a hospital-only medication, Dzuveo storage is managed entirely by the pharmacy and nursing staff at the healthcare facility. Patients do not store or handle this medication at home. Nevertheless, the following storage requirements apply:

• Keep out of reach of children at all times. As a potent opioid, even a single accidental dose could cause fatal respiratory depression in a child.
• Store in the original packaging (sealed pouch) until immediately before use. The product is sensitive to both light and oxygen, and exposure can affect its stability.
• Do not use after the expiry date printed on the label and carton. The expiry date refers to the last day of the stated month.
• Do not use if the pouch seal is broken or if the applicator appears damaged in any way.

Used and unused applicators must be disposed of according to the hospital's controlled substance disposal procedures and applicable regulatory requirements. This ensures both environmental protection and prevention of diversion or misuse.

What Does Dzuveo Contain?

Each Dzuveo sublingual tablet contains 30 micrograms of sufentanil (as citrate) as the active ingredient, along with several inactive excipients. The tablets are small (3 mm diameter), blue, flat-sided with rounded edges, and are enclosed in a single-dose applicator.

Active Ingredient

The active substance is sufentanil. Each sublingual tablet contains 30 micrograms of sufentanil (as sufentanil citrate). Sufentanil is a highly potent synthetic opioid agonist with a chemical structure related to fentanyl. It acts primarily at mu-opioid receptors in the central nervous system to produce profound analgesia.

Inactive Ingredients (Excipients)

The other ingredients are:

• Mannitol (E421) – a sugar alcohol used as a tablet filler and sweetener
• Dicalcium phosphate – a mineral salt used as a tablet diluent
• Hypromellose – a cellulose derivative used as a binder
• Croscarmellose sodium – a disintegrant that helps the tablet break down under the tongue
• Indigo carmine (E132) – a blue colouring agent for tablet identification
• Stearic acid – a lubricant used during tablet manufacture
• Magnesium stearate – a lubricant used during tablet manufacture

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per tablet, meaning it is essentially "sodium-free". This is relevant for patients on a sodium-restricted diet.

Tablet Appearance and Packaging

Dzuveo sublingual tablets are blue, flat-sided with rounded edges, and measure 3 mm in diameter. Each tablet is enclosed inside a clear plastic single-dose applicator, which is marked with "[sublingual tablet]". The applicator is sealed in a protective pouch that also contains an oxygen-absorbing packet.

Each carton contains either 5 or 10 pouches, each containing one applicator with one 30 microgram sublingual tablet. Not all pack sizes may be available in your country.

Marketing Authorisation Holder

The marketing authorisation for Dzuveo is held by Laboratoire Aguettant, 1 rue Alexander Fleming, 69007 Lyon, France. Manufacturing is also carried out at the same address and at a second facility in Champagne, France.

How Does Dzuveo Work in the Body?

Dzuveo works by delivering sufentanil through the sublingual mucosa directly into the bloodstream. Sufentanil binds to mu-opioid receptors in the brain and spinal cord, inhibiting pain signal transmission and altering the perception of pain. It is 5–10 times more potent than fentanyl and 500–1000 times more potent than morphine.

Sufentanil is a fully synthetic opioid agonist that was developed as an analogue of fentanyl. Its extreme potency arises from its high affinity and selectivity for the mu-opioid receptor, which is the primary receptor responsible for opioid-mediated analgesia. When sufentanil binds to mu-opioid receptors in the central nervous system, it activates intracellular signalling pathways that lead to reduced neuronal excitability, decreased release of excitatory neurotransmitters, and inhibition of pain signal transmission along ascending pain pathways.

The analgesic effect of sufentanil involves multiple levels of the nervous system. At the spinal cord level, it inhibits the release of substance P and other pain-mediating neurotransmitters from primary afferent neurones. At the brainstem level, it activates descending pain-inhibitory pathways. At the cortical level, it alters the emotional perception of pain, reducing suffering and distress. Together, these mechanisms produce profound analgesia that is appropriate for managing moderate-to-severe postoperative pain.

Pharmacokinetic Profile

After sublingual administration of a 30-microgram Dzuveo tablet, sufentanil is absorbed through the highly vascularised sublingual mucosa directly into the systemic circulation. This route bypasses hepatic first-pass metabolism, which is one of the key advantages over oral administration. Peak plasma concentrations are reached approximately 40–60 minutes after dosing.

The sublingual bioavailability of sufentanil from Dzuveo is approximately 59%, which is considerably higher than would be expected from oral swallowing (oral bioavailability is low due to extensive first-pass metabolism). Sufentanil is highly protein-bound (approximately 92%, primarily to alpha-1 acid glycoprotein and albumin) and has a large volume of distribution.

Sufentanil is extensively metabolised in the liver, primarily by the CYP3A4 enzyme, to the inactive metabolite desmethyl-sufentanil. Less than 2% of the dose is excreted unchanged in the urine. The terminal elimination half-life following sublingual administration is approximately 2.5 hours, although the clinical duration of effect may vary depending on the individual patient and the surgical context.

Frequently Asked Questions About Dzuveo