Sublimaze Side Effects

Generic name: fentanyl

Medically reviewed by Drugs.com. Last updated on Mar 14, 2025.

Note: This document provides detailed information about Sublimaze Side Effects associated with fentanyl. Some dosage forms listed on this page may not apply specifically to the brand name Sublimaze.

Applies to fentanyl: transdermal patch extended release.

Other dosage forms:

• lozenge/troche, spray, tablet
• injection solution
• nasal spray

Important warnings This medicine can cause some serious health issues

Transdermal route (patch, extended release)

Addiction, Abuse, and Misuse; Risk Evaluation and Mitigation Strategy (REMS); Life-threatening Respiratory Depression; Accidental Exposure; Neonatal Opioid Withdrawal Syndrome; Cytochrome P450 3A4 Interaction; Risk of Increased Fentanyl Absorption with Application of External Heat; and Risks From Concomitant Use of Benzodiazepines or Other CNS Depressants. Fentanyl exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death.

Assess patient’s risk before prescribing, and monitor regularly for these behaviors or conditions.To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products.Serious, life-threatening, or fatal respiratory depression may occur.

Monitor closely, especially upon initiation or following a dose increase.Accidental exposure to fentanyl, especially in children, can result in fatal overdose of fentanyl.Prolonged use of fentanyl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.

If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl.Exposure of the fentanyl application site and surrounding area to direct external heat sources has resulted in fatal overdose of fentanyl.

Warn patients to avoid exposing the fentanyl application site and surrounding area to direct external heat sources.Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Transdermal route (patch, device assisted)

Warning: Life-Threatening Respiratory Depression; Ionsys REMS; Addiction, Abuse, and Misuse; Cytochrome P450 3A4 Interaction; and Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants. Serious, life-threatening, or fatal respiratory depression may occur.

Monitor closely, especially upon initiation.

Only the patient should activate dosing.Fentanyl iontophoretic transdermal system is for use only in patients in the hospital.

Discontinue fentanyl iontophoretic transdermal system before patients leave the hospital.Because of the risk of respiratory depression from accidental exposure, fentanyl iontophoretic transdermal system is available through a restricted program called the fentanyl iontophoretic transdermal system REMS Program.

Healthcare facilities that dispense fentanyl iontophoretic transdermal system must be certified in this program and comply with the REMS requirements.Fentanyl iontophoretic transdermal system exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death.

Assess patient’s risk before prescribing, and monitor regularly for these behaviors and conditions.Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl.Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Precautions

It is very important that your doctor check your or your child's progress while using this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may needed to check for unwanted effects.

Do not touch the sticky side of the patch or the gel. Fentanyl can be quickly absorbed through the eyes and mouth and can be extremely dangerous. If you do touch the sticky side of the patch or gel, let your nurse or doctor know right away and rinse the area with large amounts of water. Do not use soaps or other cleansers.

Check with your doctor at regular times while using fentanyl (the active ingredient contained in Sublimaze) Be sure to report any side effects.

After you have been using this medicine for awhile, "breakthrough" pain may occur more often than usual, and it may not be relieved by your regular dose of medicine. If this occurs, do not increase the amount of fentanyl skin patch or other narcotic that you are using without first checking with your doctor.

This medicine will add to the effects of alcohol and other CNS depressants. CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, benzodiazepines, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. This effect may last for a few days after you stop using this medicine. Check with your doctor before taking any of the medicines listed while you are using this medicine.

The Ionsys® patch must be removed before a procedure called a magnetic resonance imaging (MRI) scan. It may cause skin burns if left in place during the procedure.

The Ionsys® patch may cause serious skin reactions. Call you doctor right away if you have blistering, lesions, a rash, redness, or swelling of the skin, especially at the site of application.

Fentanyl may cause some people to become drowsy, dizzy, or lightheaded, or to feel a false sense of well-being. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. These effects usually go away after a few days of treatment, when your body gets used to the medicine. However, check with your doctor if drowsiness that is severe enough to interfere with your activities continues for more than a few days.

Dizziness, lightheadedness, or even fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve dizziness or lightheadedness.

Nausea or vomiting may occur, especially during the first several days of treatment. Lying down for a while may relieve these effects. However, if they are especially bothersome or if they continue for more than a few days, check with your doctor. You may be able to take another medicine to help prevent these problems.

Using narcotics for a long time may 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.

Heat can cause the fentanyl in the patch to be absorbed into your body faster. This may increase the chance of serious side effects or an overdose. While you are using this medicine, do not use a heating pad, electric blanket, heat or tanning lamps, sauna, a sunlamp, or a heated water bed, and do not sunbathe, or take long baths or showers in hot water. Also, check with your doctor if you get a fever.

Be careful about letting other people come in contact with your patch. The patch could stick to someone else, such as when you hug them or if someone helps you put the patch on. If any medicine gets on another person, wash it off right away with clear water.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine. Serious side effects can occur if your medical doctor or dentist gives you certain other medicines without knowing that you are using fentanyl.

You may bathe, shower, or swim while wearing a fentanyl skin patch. However, be careful to wash and dry the area around the patch gently. Rubbing may cause the patch to get loose or come off. If this does occur, throw away the patch and apply a new one in a different place. Make sure the area is completely dry before applying the new patch.

If you have been using this medicine regularly for several weeks or more, do not suddenly stop using it without first checking with your doctor. You may be directed to gradually reduce the amount you are using before stopping treatment completely to lessen the chance of withdrawal side effects.

Using too much fentanyl skin patch, or taking too much of another narcotic with fentanyl skin patch, may cause an overdose. If this occurs, get emergency help right away. An overdose can cause severe breathing problems (breathing may even stop), unconsciousness, and death. Serious signs of an overdose include: very slow breathing (fewer than 8 breaths a minute) and drowsiness that is so severe that you are not able to answer when spoken to, or, if asleep, cannot be awakened. Other signs of an overdose may include: cold, clammy skin, low blood pressure, pinpoint pupils of the eyes, and slow heartbeat. It may be best to have a family member or a friend check on you several times a day when you start using a narcotic regularly, and whenever your dose is increased, so that he or she can get help for you if you cannot do so yourself.

This medicine may cause sleep-related breathing problems (eg, sleep apnea, sleep-related hypoxemia). Your doctor may decrease your dose if you have sleep apnea (stop breathing for short periods during sleep) while using this medicine.

Do not use a fentanyl patch if you have taken a monoamine oxidase (MAO) inhibitor in the past 2 weeks. Some examples of MAO inhibitors are isocarboxazid (Marplan®), phenelzine (Nardil®), selegiline (Eldepryl®), and tranylcypromine (Parnate®). If you use the 2 medicines close together it may cause serious side effects like confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high temperature, an extremely high blood pressure, or severe convulsions.

Check with your doctor right away if you 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.

Using this medicine while you are pregnant may cause serious unwanted effects, including neonatal opioid withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

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

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.

Common side effects of Sublimaze

Some side effects of fentanyl may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common side effects

• constipation
• feeling cold
• sleepiness or unusual drowsiness
• trouble sleeping

Less common side effects

• dry mouth
• feeling of constant movement of self or surroundings
• feeling of crawling, tingling, or burning of the skin
• lack or loss of strength
• memory loss
• sensation of spinning
• unusual dreams

Rare side effects

• abnormal ejaculation
• decreased interest in sexual intercourse
• decreased sexual performance or desire
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• muscle twitching

Incidence not known

• belching
• heartburn
• indigestion
• stomach discomfort or upset

Serious side effects of Sublimaze

Along with its needed effects, fentanyl 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 immediately if any of the following side effects occur while taking fentanyl:

Less common side effects

• anxiety
• bloating or swelling of the face, arms, hands, lower legs, or feet
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• confusion
• decrease in urine volume
• difficulty in breathing or swallowing
• difficulty in passing urine (dribbling)
• fast, irregular, pounding, or racing heartbeat or pulse
• painful urination
• rapid weight gain
• seeing, hearing, or feeling things that are not there
• skin itching, rash, or redness
• swelling of the face, throat, or tongue
• tremor
• unusual weight gain or loss
• upper stomach pain

Rare side effects

• bluish color of the fingernails, lips, skin, palms, or nail beds
• burning, itching, redness, skin rash, swelling, or soreness at the application site
• confusion about identity, place, and time
• false or unusual sense of well-being
• irregular, fast or slow, or shallow breathing

Incidence not known

• agitation
• blurred vision
• chest pain or discomfort
• cough
• darkening of the skin
• diarrhea
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fever
• headache
• hives
• lightheadedness, dizziness, or fainting
• loss of appetite
• mental depression
• nausea
• nervousness
• overactive reflexes
• poor coordination
• pounding in the ears
• restlessness
• severe constipation
• severe vomiting
• shivering
• sweating
• talking or acting with excitement you cannot control
• tightness in the chest
• unusual tiredness or weakness
• vomiting

Get emergency help immediately if any of the following symptoms of overdose occur while taking fentanyl:

Symptoms of overdose

• cold, clammy skin
• drowsiness that is so severe you are not able to answer when spoken to or, if asleep, cannot be awakened
• pinpoint (small) pupils in the eyes
• seizures
• slow heartbeat
• very slow or troubled breathing

For healthcare professionals

Applies to fentanyl: buccal film, buccal tablet, compounding powder, injectable solution, intravenous solution, nasal spray, oral lozenge, oral transmucosal lozenge, sublingual spray, sublingual tablet, transdermal device, transdermal film extended release.

General adverse events

The most commonly reported adverse reactions included headache, nausea, vomiting, ,dizziness, and constipation.^[Ref]

Nervous system

• Very common (10% or more): Somnolence, dizziness
• Common (1% to 10%): Sedation, pyrexia, fatigue, lethargy, tremor, headache, chills, irritability, malaise, confusion, abnormal thinking, anxiety, dysphoria
• Uncommon (0.1% to 1%): Hyperesthesia
• Very rare (less than 0.01%): Severe hemiplegic migraine
• Frequency not reported: Slurred speech, paresthesia, hypesthesia, tremor
• Postmarketing reports: Loss of consciousness, vertigo, coma, shock, convulsion^[Ref]

Cases of seizures have occasionally been reported, but some investigators have suggested that the seizure-like events reported may have been episodes of fentanyl induced-rigidity.^[Ref]

Cardiovascular

• Common (1% to 10%): Tachycardia
• Uncommon (0.1% to 1%): Sinus tachycardia, chest pain, hypertension, hypotension, palpitations
• Rare (less than 0.1%): Arrhythmias, cardiac arrest
• Frequency not reported: Syncope, vasodilation, bradycardia, bigeminy, myocardial infarct
• Postmarketing reports: Circulatory depression^[Ref]

One report has suggested that epidural fentanyl may mask the pain of myocardial ischemia in patients treated with fentanyl for other reasons. Another report has suggested that QTc interval prolongation may occur in some patients receiving the related narcotic sufentanil. Another report has implicated fentanyl as a potential cause of pulsus alternans in a patient with aortic stenosis and congestive heart failure.

Nevertheless, fentanyl has been advocated by some as a satisfactory agent for coronary artery surgery.^[Ref]

Gastrointestinal

• Very common (10% or more): Nausea (18%), vomiting (10%), constipation
• Common (1% to 10%): Dry mouth, abdominal distension, gastritis, dysphagia, dyspepsia, gastroesophageal reflux disease, ascites, hematemesis, taste perversion, abdominal pain, dehydration, anorexia, cachexia, vomiting, dry mouth, mouth ulcers/stomatitis, tongue edema
• Uncommon (0.1% to 1%): Abdomen enlarged, flatulence
• Rare (less than 0.1%): Choledochoduodenal sphincter spasm
• Frequency not reported: Diarrhea
• Postmarketing reports: Ileus, dental caries, tooth loss, gingival recession, gingivitis, gingival bleeding, lip edema, pharyngeal edema, gum bleeding, ulcer^[Ref]

Genitourinary

• Uncommon (0.1% to 1%): Urinary retention
• Very rare (less than 0.01%): Priapism
• Frequency not reported: Urinary tract infection, urination impaired, hematuria, urinary urgency, dysuria^[Ref]

Dermatologic

• Very common(10% or more): Iontophoretic transdermal system: Application site reaction-Erythema (14%)
• Common (1% to 10%): Application site irritation, pruritus
• Uncommon (0.1% to 1%): Hyperhidrosis, rash
• Rare (less than 0.1%): Systemic rashes
• Frequency not reported: vesicles, papules/pustules, dry and flaky skin, vesiculobullous rash wound site oozing/bleeding, wound site inflammation/erythema
• Postmarketing reports: Application site discharge, application site bleeding, application site infection, rash and scab, erosion, hyperesthesia, application site necrosis^[Ref]

Approximately 60% of patients had some redness at the skin site 24-hours after removal of the iontophoretic transdermal system. The majority of skin events were categorized as mild, erythema and papules were observed; 2 patients had hyperpigmentation at the application site lasting 2 to 3 weeks; 3 patients had a rectangular mark at the application site which persisted for up to 3 months.^[Ref]

Hypersensitivity

• Rare (less than 0.1%): Anaphylaxis^[Ref]

Hematologic

• Common (1% to 10%): Anemia, neutropenia, lymphadenopathy, thrombocytopenia, leukopenia, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood glucose increased, blood lactate increased, hypoalbuminemia, vasodilation^[Ref]

The hemolysis observed may have been related to rapid injection of large volumes of hypotonic fentanyl (the active ingredient contained in Sublimaze) solution. The authors therefore recommend slower injection rates and/or mixture in isotonic fluid.^[Ref]

Immunologic

• Uncommon (0.1% to 1%): Oral candidiasis, cellulitis, pneumonia, urinary tract infection, oral herpes, gastroenteritis, laryngitis
• Very rare (less than 0.01%): Recurrent herpes simplex infection following epidural administration^[Ref]

Metabolic

• Common (1% to 10%): Asthenia, peripheral edema, weight decreased, hypokalemia, hyponatremia, hypocalcemia
• Very rare (less than 0.01%): Syndrome of inappropriate antidiuretic hormone
• Frequency not reported: abnormal healing, dehydration^[Ref]

Endocrine

• Uncommon (0.1% to 1%): Hot flush^[Ref]

Musculoskeletal

• Common (1% to 10%): Fall/accidental injury, back pain, arthralgia, joint swelling, muscular weakness, myoclonus, involuntary muscle contractions, muscle rigidity (involving the respiratory musculature including the glottis)
• Frequency not reported: Leg cramps, myalgia
• Postmarketing reports: Abnormal gait/incoordination^[Ref]

Ocular

• Uncommon (0.1% to 1%): Vision blurred, dry eye
• Rare (less than 0.1%): Abnormal vision^[Ref]

Psychiatric

• Common (1% to 10%): Depression, confusional state, hallucination, insomnia
• Uncommon (0.1% to 1%): Anxiety, agitation, restlessness, agitation, disorientation, abnormal dreams, depersonalization, depression, emotional lability, euphoria, delirium
• Frequency not reported: Nervousness^[Ref]

Respiratory

• Common (1% to 10%): Dyspnea, rhinitis, yawning, respiratory distress, apnea, bradypnea, hypoventilation, respiratory depression
• Uncommon (0.1% to 1%): Cough, increased bronchial secretion, dysphonia, pharyngolaryngeal pain, wheezing, hypoxia, exertional dyspnea
• Very rare (less than 0.01%): Acute noncardiogenic pulmonary edema
• Frequency not reported: Asthma, hiccup, atelectasis, hyperventilation
• Postmarketing reports: Respiratory arrest^[Ref]

See also:

Frequently asked questions

• Which drugs cause opioid-induced constipation?
• How long does Fentanyl stay in your system?
• Why is fentanyl so dangerous?
• Carfentanil vs Fentanyl: Which is more dangerous?
• Fentanyl test strips: where to get & how to use?
• Which painkiller should you use?
• What are the symptoms of a fentanyl overdose?
• How does fentanyl compare to heroin or other opiates?

Further information

Sublimaze side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer