FDA ALERT [7/2005]:   Narcotic Overdose and Death

FDA is looking into reports of death and other serious side effects from overdoses of the narcotic fentanyl in patients using the fentanyl transdermal skin patches for pain control.  Directions for using the fentanyl skin patch must be followed exactly to prevent death or other severe side effects that can happen from using too much (overdosing) fentanyl. These directions are provided in the patient package insert, available at this link and highlighted below: http://www.fda.gov/cder/drug/infopage/fentanyl/DuragesicPPI.pdf.

This information reflects FDA’s preliminary analysis of data concerning this drug.   FDA is considering, but has not reached a final conclusion about this information. FDA intends to update this sheet when additional information or analyses become available.

What is the Fentanyl Transdermal System?

Fentanyl Transdermal System (skin patch) is a prescription medicine that is a federally controlled substance (CII) because it is a strong pain medicine that can be abused by people who abuse prescription medicines or street drugs.

• The fentanyl skin patch is only for patients with chronic (around the clock) pain that is moderate to severe and expected to last for weeks or longer.
• The fentanyl skin patch should not be the first opioid (narcotic) pain medicine that is prescribed for your pain. You should ONLY use the fentanyl skin patch if you have been taking at least 60 milligrams (mg) of oral morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily, or an equally strong dose of another opioid for a week or longer before starting the fentanyl skin patch.
• The fentanyl skin patch is not for patients who need opioid pain medicines for only a short time. This includes the pain that happens with surgery (such as tonsillectomies), medical, or dental procedures (such as wisdom tooth removal).
• The fentanyl skin patch is not for occasional ("as needed") use.
• The fentanyl skin patch is only for opioid tolerant children 2 years of age or older who are already using other opioid narcotic pain medicines. Pediatric patients 2 years of age or older are opioid tolerant if they are taking at least 60 milligrams (mg) of oral morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily, or an equally strong dose of another opioid for a week or longer before starting the fentanyl skin patch.

Who Should Not Use the Fentanyl Skin Patch?  

Do not use the fentanyl skin patch:

• If you are NOT already using other opioid narcotic medicines.
• If you need opioid pain medicines for only a short time.
• For pain from surgery, medical or dental procedures.
• If your pain can be taken care of by occasional use of other pain medicines.
• In children who are less than 2 years of age.
• In children 2 years of age or older who are not already using other opioid narcotic pain medicines (opioid tolerant).
• If you have acute (sudden) or severe asthma.
• If you have a gastrointestinal problem called paralytic ileus.

What are The Risks?

The following are the major possible risks and side effects of fentanyl skin patch therapy. This list is not complete.

The fentanyl skin patch can cause serious problems that you should tell your doctor or healthcare professional about immediately such as:

• Trouble breathing, which can be fatal. Call your healthcare professional right away or get emergency medical help if you:
  • Have trouble breathing
  • Have extreme drowsiness with slowed breathing
  • Have shortness of breath (little chest movement with breathing)
  • Feel faint, dizzy, confused, or have other unusual symptoms .   These can be symptoms that you have taken too much (overdose) fentanyl or the dose of fentanyl in the skin is too high for you. These symptoms may lead to serious problems or death if not treated right away.
• Physical Dependence. Stopping the fentanyl skin patch suddenly can make you sick with withdrawal symptoms. Talk to your healthcare professional about slowly stopping the fentanyl skin patch.
• Addiction. There is a chance you could get addicted to the fentanyl skin patch. The chance is higher if you are or have been addicted to or abused other medicines, street drugs, or alcohol, or if you have a history of mental problems.
• Drop in blood pressure. This can make you feel dizzy if you get up too fast from sitting or lying down.
• Common side effects with the fentanyl skin patch are nausea, vomiting, constipation, dry mouth, sleepiness, confusion, weakness, and sweating.
• Constipation is a very common side effect of opioids including the fentanyl skin patch and is unlikely to go away without treatment. Talk to your healthcare professional about the use of laxatives (medicines to treat constipation) and stool softeners to prevent or treat constipation while using the fentanyl skin patch.
• Sleepiness. The fentanyl skin patch can make you sleepy. Do not drive, operate heavy machinery, or do any other possibly dangerous activities until you know how the fentanyl skin patch affects you.   
• Other: Although uncommon, trouble sleeping and seizures were reported in children.

What Should I Tell My Healthcare Professional?

Before you use the fentanyl skin patch, tell your healthcare professional about all of your medical problems, especially if you have:

• Trouble breathing or lung problems such as asthma, wheezing, or shortness of breath.
• A head injury or brain problems.
• A heart problem called bradycardia (slow heart beat).
• Liver or kidney problems.
• Seizures (convulsions or fits).
• Gallbladder problems.
• Low thyroid (hypothyroidism).
• Low blood pressure.
• Problems urinating.
• Major depression.
• Hallucinations (seeing or hearing things that are not seen by other people) adrenal gland problems such as Addison’s disease.
• A past or present drinking problem or alcoholism, or a family history of this problem.
• A past or present drug abuse or addiction problem, or a family history of this problem.
• Skin reactions to the adhesives (glues) used in the fentanyl skin patch.
• Are pregnant or planning to become pregnant. The fentanyl skin patch may harm your unborn baby.
• Are breast feeding. The medicine in the fentanyl skin patch passes into your milk and can harm your baby.
• Use heating sources such as heating pads, electric blankets, heat lamps, saunas, hot tubs, or heated waterbeds. Do not take long hot baths or sun bathe. All of these can make your temperature rise and cause too much of the medicine in the fentanyl skin patch to be released at once and this can be dangerous.

Can Other Medicines or Foods Affect the Fentanyl Skin Patch?

Some medicines may cause serious or life-threatening side effects when used with the fentanyl skin patch. Tell your healthcare professional about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Sometimes, the doses of certain medicines and the fentanyl skin patch need to be changed when used together. Be especially careful about other medicines that make you sleepy such as other pain medicines, sleeping pills, anxiety medicines, antihistamines, or tranquilizers. Do not start any new prescription medicine, non-prescription medicine, or herbal supplement while using the fentanyl skin patch until you have talked to your healthcare professional.

What Else Should I know About the Fentanyl Skin Patch?

• Call your healthcare professional right away if you get a fever higher than 102°F. A fever may cause too much of the medicine in the fentanyl skin patch to pass into your body. Your healthcare professional may tell you to use a lower dose while you have a fever.
• Do not use the fentanyl skin patch if the seal is broken or the patch is cut, damaged or changed in any way. Using a patch that is cut, damaged, or changed in any way can expose you to the contents of the patch, which contains a potentially fatal dose of medicine.
• Do not change your dose or stop using the fentanyl skin patch unless your healthcare professional tells you to.
• Do not use the fentanyl skin patch more often than prescribed.
• Do not wear more than one fentanyl skin patch at a time, unless your healthcare professional tells you to do so.
• After you have stopped using a patch, be sure to fold the sticky sides of the patch together and flush it down the toilet. Do not put used fentanyl skin patches in a garbage can.
• If your healthcare professional tells you to stop using the fentanyl skin patch, throw away the unused packages. Open the unused packages and fold the sticky sides of the patches together, and flush them down the toilet.

Recommendations

Health Care Professionals who prescribe the fentanyl transdermal patch should be fully aware of all the prescribing information in the product label.   FDA is highlighting safety information from the product label here:

• Fentanyl transdermal patches are potent opioid analgesics that may cause death from overdose.  The fentanyl transdermal patch should always be prescribed at the lowest dose needed for pain relief.  

• Fentanyl transdermal patches should not be used to treat short-term pain, pain that is not constant, or pain after an operation.   Fentanyl transdermal patches should only be used by opiod tolerant patients who are already taking other narcotic analgesics, and who have chronic pain that is not well controlled with shorter-acting analgesics.  

• Patients who are using the fentanyl transdermal patch and their caregiversmust be fully informedabout the directions for safe use of the patch.   These directions are provided in the product label and in the patient package insert, available at this link: http://www.fda.gov/cder/drug/infopage/fentanyl/DuragesicPPI.pdf

• Patients who are using the fentanyl transdermal patch and their caregiversmust be fully informedabout safe methods for storage and disposal of used, unneeded or defective fentanyl transdermal patches.    Fentanyl transdermal patches should be stored in a safe place and kept out of the reach of children.   Safely dispose of used, unneeded or defective fentanyl transdermal patchesby folding the adhesive sides of the patch together (until it adheres to itself) and flushing it down the toilet.  

• Health care professionals who prescribe the fentanyl transdermal patch and patients who use the fentanyl transdermal patch and their caregivers should be aware of the signs of fentanyl overdose. Signs of fentanyl overdose include trouble breathing or shallow breathing; tiredness, extreme sleepiness or sedation; inability to think, talk or walk normally; and feeling faint, dizzy or confused.    If these signs occur, patients or their caregivers should get medical attention right away.  

• A patient using the fentanyl transdermal patch may have a sudden and possible dangerous rise in their body level of fentanyl or have a more potent fentanyl effect if they: use other sedating medicines; drink alcohol (beer, wine or distilled spirits); have an increase in body temperature or are exposed to heat; or use other medicines that increase the elimination half-life of fentanyl (such as cytochrome P450 3A4 inhibitors).   

Data Summary

FDA recently conducted a review of fatalities reported to the voluntary adverse event reporting system that were possibly due to unintentional overdose from the fentanyl transdermal patch. In many cases, establishing whether the overdose was unintentional was difficult, because the information provided in the report was incomplete and patients who were being treated with the fentanyl patch often had underlying diseases or conditions that could have contributed to their deaths (such as cancer). Factors identified as possibly related to unintentional overdose included: use of high doses of the fentanyl patch and/or multiple patches (sometimes in combination with other drugs), possible medication errors, accidental exposure (e.g., coming in contact with a discarded patch), application of a heat source to the patch possibly resulting in increased fentanyl absorption, injection or ingestion of the patch contents, and suspected transdermal patch malfunction (e.g., leaking patches). In addition, several patients reported poor adhesion of the patches to the skin.

The Duragesic product label addresses issues regarding proper use of the product (e.g., risk of abuse and diversion, avoidance of direct heat sources to the patch, proper disposal of a discarded patch). FDA continues to work with the manufacturers of these products to identify and manage factors that contribute to fentanyl overdose from use of the fentanyl transdermal patch.

Recommendations

Health Care Professionals who prescribe the fentanyl transdermal patch should be fully aware of all the prescribing information in the product label.   FDA is highlighting safety information from the product label here:

• Fentanyl transdermal patches are potent opioid analgesics that may cause death from overdose.  The fentanyl transdermal patch should always be prescribed at the lowest dose needed for pain relief.  

• Fentanyl transdermal patches should not be used to treat short-term pain, pain that is not constant, or pain after an operation.   Fentanyl transdermal patches should only be used by opiod tolerant patients who are already taking other narcotic analgesics, and who have chronic pain that is not well controlled with shorter-acting analgesics.  

• Patients who are using the fentanyl transdermal patch and their caregiversmust be fully informedabout the directions for safe use of the patch.   These directions are provided in the product label and in the patient package insert, available at this link: http://www.fda.gov/cder/drug/infopage/fentanyl/DuragesicPPI.pdf

• Patients who are using the fentanyl transdermal patch and their caregiversmust be fully informedabout safe methods for storage and disposal of used, unneeded or defective fentanyl transdermal patches.    Fentanyl transdermal patches should be stored in a safe place and kept out of the reach of children.   Safely dispose of used, unneeded or defective fentanyl transdermal patchesby folding the adhesive sides of the patch together (until it adheres to itself) and flushing it down the toilet.  

• Health care professionals who prescribe the fentanyl transdermal patch and patients who use the fentanyl transdermal patch and their caregivers should be aware of the signs of fentanyl overdose. Signs of fentanyl overdose include trouble breathing or shallow breathing; tiredness, extreme sleepiness or sedation; inability to think, talk or walk normally; and feeling faint, dizzy or confused.    If these signs occur, patients or their caregivers should get medical attention right away.  

• A patient using the fentanyl transdermal patch may have a sudden and possible dangerous rise in their body level of fentanyl or have a more potent fentanyl effect if they: use other sedating medicines; drink alcohol (beer, wine or distilled spirits); have an increase in body temperature or are exposed to heat; or use other medicines that increase the elimination half-life of fentanyl (such as cytochrome P450 3A4 inhibitors).   

Data Summary

FDA recently conducted a review of fatalities reported to the voluntary adverse event reporting system that were possibly due to unintentional overdose from the fentanyl transdermal patch. In many cases, establishing whether the overdose was unintentional was difficult, because the information provided in the report was incomplete and patients who were being treated with the fentanyl patch often had underlying diseases or conditions that could have contributed to their deaths (such as cancer). Factors identified as possibly related to unintentional overdose included: use of high doses of the fentanyl patch and/or multiple patches (sometimes in combination with other drugs), possible medication errors, accidental exposure (e.g., coming in contact with a discarded patch), application of a heat source to the patch possibly resulting in increased fentanyl absorption, injection or ingestion of the patch contents, and suspected transdermal patch malfunction (e.g., leaking patches). In addition, several patients reported poor adhesion of the patches to the skin.

The Duragesic product label addresses issues regarding proper use of the product (e.g., risk of abuse and diversion, avoidance of direct heat sources to the patch, proper disposal of a discarded patch). FDA continues to work with the manufacturers of these products to identify and manage factors that contribute to fentanyl overdose from use of the fentanyl transdermal patch.

Date created: July 15, 2005