The Duragesic (Fentanyl) Pain Patch: One Very Dangerous Drug

By Steven Di Joseph -

Although prescription and over-the-counter (OTC) painkillers have become commonplace, and are taken by tens of millions of Americans for every imaginable (and even imaginary) kind of pain, often without a second thought, at 80 times the potency of morphine, fentanyl is extremely dangerous and potentially lethal when improper amounts of the drug are dispensed. To be sure, Fentanyl is a drug that is not to be taken lightly.

Unlike drugs that are taken orally (in liquid or pill form) or by measured injection, fentanyl is released through the skin in a steady dose over an extended period by means of an adhesive patch. As a result, a great deal of trust must be placed in the ability of each patch to work perfectly. Anything short of that can cause the user to quickly suffer extreme distress or death.

In fact, at least one medical examiner has stated that a lethal dose of fentanyl can occur so swiftly there may not even be time to call for emergency medical assistance.

Since each patch contains considerably more fentanyl than any patient can safely take in a short period of time, a damaged patch or one that has a cut in it can pose a serious health risk to the user. Moreover, a manufacturing defect in any one patch or in an entire lot of patches may not even be detected until it is too late.

Between 1994 and 2008, the Duragesic Fentanyl Patch, which is also referred to as the Fentanyl Transdermal System, was recalled five times. In July 2005, the fifth recall followed the death of 120 patch users.

Fentanyl patches come in a variety of dosages (indicated by mcg/hr or micrograms per hour) including, 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, and 100 mcg/hr. Clearly, one of the first potential dangers associated with these patches is the possibility of errors involving the dosage. A 100 mcg/hr patch is four times the dosage per hour of a 25 mcg/hr patch. Thus, confusing the two can have deadly effects.

Another problem associated with these patches is their misuse by patients who hold onto unused patches and then give them to other people experiencing pain as if they are nothing more that OTC painkillers like aspirin, Tylenol, Bufferin, or Advil. In May 2005, a six-year-old girl reportedly died after being given a Duragesic patch for her neck pain.

In 2008, there were multiple recalls of various fentanyl patches manufactured by a number of companies. In February 2008, Johnson & Johnson’s Ortho-McNeil-Janssen unit recalled all lots of its 25 mcg/hr Duragesic pain patch. A month after, Actavis issued an expanded recall that included all of its fentanyl patches sold in the United States (25, 50, 75, and 100 mcg/hr). Immediately thereafter, the PriCara Division of Ortho-McNeil-Janssen issued a voluntary recall of all of its 25 mcg/hr Duragesic CII patches sold by PriCara in the U.S. and all 25 mcg/hr fentanyl patches sold by Sandoz Inc. in the U.S. as a precaution.

The problem being encountered with all of these patches is the possibility that leakage, caused by manufacturing defects, may lead to overdosing with fentanyl.

The FDA has required a Black Box Warning for all fentanyl patches and on December 21, 2007, the FDA issued a Public Health Advisory, which stated in part:

FDA is investigating reports of death and other serious side effects from overdoses of fentanyl in patients using fentanyl transdermal (skin) patches for pain control. Deaths and overdoses have occurred in patients using both the brand name product Duragesic and the generic product. The directions for using the fentanyl skin patch must be followed exactly to prevent death or other serious side effects from overdosing with fentanyl. These directions are provided in the product label and patient package insert.

Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information:

• Fentanyl skin patches are very strong narcotic (opioid) painkillers that may cause death from overdose. The fentanyl skin patch should always be prescribed at the lowest dose needed for pain relief.
• Fentanyl skin patches should not be used to treat short-term pain, pain that is not constant, or for pain after an operation. Fentanyl skin patches should only be used by patients who are already taking other narcotic painkillers (opioid tolerant), and who have chronic pain that is not well controlled with shorter-acting painkillers.
• Patients who are using the fentanyl skin patch and their caregivers should be told about the directions for safe use of the patch and should follow the directions exactly. These directions are provided in the patient package insert
• Patients who are using the fentanyl skin patch and their caregivers should be told about safe methods for storage and disposal of used, unneeded or defective fentanyl skin patches. Fentanyl skin patches should be stored in a safe place and kept out of the reach of children. Safely dispose of used, unneeded or defective fentanyl skin patches by folding the sticky side of the patch together (until it sticks to itself) and flushing it down the toilet.
• Health care professionals who prescribe the fentanyl skin patch and patients who use the fentanyl skin 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 skin patch may have a sudden and possible dangerous rise in their body level of fentanyl or have a stronger effect from fentanyl if they: use other medicines that affect brain function; drink alcohol (beer, wine or distilled spirits); have an increase in body temperature or are exposed to heat; or use other medicines that affect how fentanyl is broken down in the body. These factors are described further in the product label.

In June 2005 the Duragesic product label was updated to add new safety information in several areas of labeling, and a “Dear Healthcare Professional” letter about these changes was issued by the manufacturer and is available at this link (http://www.fda.gov/medwatch/SAFETY/2005/duragesic_ddl.pdf). 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 skin patch. Updates will be provided as new information is available.

Finally, the Drug Profile from Worst Pills, Best Pills, published by the public watchdog organization, Public Citizen, provides the following important information and warnings:

Drug Profile

Generic drug name: fentanyl [patch] (FEN ta nil)

Brand name(s): DURAGESIC

GENERIC: not available

FAMILY: Opiate-containing Painkillers

Breast-feeding Warning

Fentanyl is excreted in human milk. Because of the potential for adverse effects in nursing infants, you should not take this drug while nursing.

PREGNANCY WARNING Fentanyl caused fetal death in animal studies. Because of the potential for serious adverse effects to the fetus, this drug should not be used by pregnant women.

Facts About This Drug:

Fentanyl is a synthetic narcotic that relieves pain. Most studies about fentanyl focus on the injectable form used during surgery. Fewer studies have been done on the transdermal (patch) form, and even fewer studies have been done on older people using fentanyl patches.

Fentanyl patches, which slowly release medication over three days, are used for are used for persistent, moderate to severe chronic pain that requires around-the-clock opioid administration for an extended period of time and cannot be managed by other means. Pain relief usually improves sleep. People with swallowing difficulties or poor veins benefit from the topical application. Others find the patch convenient. However, fentanyl is not a Band-Aid for mild or intermittent pain, and is not usually used until doses of oral morphine have become high and frequent. Using cut or damaged patches can cause a high dose of the drug to be released and absorbed, which can be fatal. The first dose of fentanyl is usually 25 micrograms (this refers to the number of micrograms released each hour). Doses must be estimated according to prior use of other analgesics. Older people usually need less fentanyl than younger people. It may take a few days until adequate pain relief is achieved. During the transition, other shorter-acting analgesics relieve breakthrough pain. One drawback of the patches is less flexibility in doses, which are currently limited to four sizes and their combinations. People who lose weight may need to have their dose lowered, since fentanyl is stored in fat tissue. Fentanyl  should not be used on as-needed basis.

Fentanyl is not recommended for those weighing less than 110 pounds. Common adverse effects of fentanyl are nausea, vomiting, constipation, and skin irritation from the adhesive on the patch. Fentanyl patches are not recommended after surgery due to risk of severe respiratory problems. Like morphine, fentanyl is a controlled substance and could be habit-forming. The cost of fentanyl patches is more than short-acting oral morphine, similar to long-acting oral morphine, and usually less than injectable morphine, which involves costs for supplies and equipment.

In July of 2005, the FDA issued a Public Health Advisory and added extensive safety warnings to the professional product label of fentanyl in response to reports of death linked to the use of the fentanyl transdermal patch. The new warnings identify several important safety precautions, which are described below.

Fentanyl skin patches should not be used in the following situations:

• in patients who have not previously been prescribed opioid painkillers
• in the management of acute pain or in patients who require opioid pain killers only for a short period of time
• in the management of post-operative pain, including use after out-patient or same-day surgeries
• in the management of mild pain
• in the management of intermittent pain

Fentanyl skin patches interact with a number of drugs that can increase the amount of fentanyl in the blood to dangerous levels. These drugs include ritonavir (KALETRA, NORVIR), ketoconazole (NIZORAL), itraconazole (SPORANOX), troleandomycin (TAO), clarithromycin (BIAXIN), nelfinavir (VIRACEPT), and nefazodone (SERZONE).

Damaged or cut fentanyl skin patches should not be used. Damage to the skin patch can lead to the rapid release of its contents and absorption of a potentially fatal dose of fentanyl.

A copy of the FDA-approved Medication Guide is available here (http://www.fda.gov/cder/drug/InfoSheets/patient/fentanylPIS.htm).

Before You Use This Drug:

Do not use if you have or have had:

• diarrhea
• respiratory depression
• are breast-feeding

Tell your doctor if you have or have had:

• allergies to medications or adhesives
• emphysema, asthma, or other lung problems
• colitis or inflammatory bowel disease
• alcohol or drug abuse
• gallbladder problems
• head injuries or brain tumor
• coma
• kidney or liver problems
• gastrointestinal problems
• thyroid problems
• slow heartbeat
• emotional problems
• suicidal ideation or attempt
• enlarged prostate or difficulty urinating
• recent urinary tract surgery
• pregnancy or are breast-feeding
• not opioid tolerant
• fever

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.

When You Use This Drug:

Read the patient instructions carefully before using.

To avoid constipation, drink plenty of water or fluids. Eat fiber. Take a stool softener. If constipation develops, you may need a laxative or enema.

Do not use more than directed by your doctor; it may take 24 hours before effects are felt.

Until you know how you react to fentanyl, avoid driving or performing other activities requiring alertness, as fentanyl can cause drowsiness.

Avoid drinking alcohol, which adds to central nervous system (CNS) effects of fentanyl.

Until your dose of fentanyl stabilizes, you may need another short-acting pain reliever for breakthrough pain.

If you plan to have any surgery, including dental, tell your doctor that you take this drug.

Do not use heating pads, electric blankets, heated water beds, hot tubs, saunas, or heat lamps. These could cause fentanyl to be too rapidly absorbed, especially if devices slip onto the patch while you sleep.

You may feel dizzy when rising from a lying or sitting position. When getting out of bed, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay beside the chair until you are sure that you are not dizzy.

If nausea develops, try lying down until it subsides.

You may wear fentanyl patches while bathing, showering, or swimming, but do not rub the patch vigorously or stay for a prolonged time in hot water. If the patch loosens or dislodges, contact your doctor.

If you sleep or nap near someone else, cover the area of the patch with clothing. Otherwise, the patch could transfer to the other person. This has caused children to receive overdoses.

How to Use This Drug:

If you miss a dose, take it as soon as possible, but skip it if it is almost time for the next dose. Do not take double doses.

Do not share your medication with others.

Take the drug at the same time(s) each day.

Prepare the site with water. Do not shave the site or use soap, alcohol, or lotions. Do not apply to areas that are burned, cut, or irritated. Clip hair if necessary.

Remove liner just before using. Take care not to touch the adhesive surface. Wash with clean water any area the medication unintentionally touches.

Do not use if seal is broken or patch is otherwise damaged or cut.

Apply entire patch to dry skin above the waist. Press firmly with palm of hand for at least 30 seconds, especially around the edges.

If applying more than one patch, do not let edges overlap or touch. Rotate site of application, preferably alternating sides of the body.

Change patch every three days, unless your doctor tells you to change at a different frequency.

Do not apply more than the prescribed dose.

Fold used patches in half with adhesive layer inside the fold. Flush down toilet or otherwise dispose of in secure manner.

Wash hands.

Do not stop using abruptly. A gradual reduction prevents withdrawal symptoms. Even if you stop using fentanyl patches, some of the drug can remain in older people for a few days.

Store at room temperature. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs:

The following drugs are listed in the Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with this drug. We have also included potentially serious interactions listed in the drug’s FDA-approved professional product labeling or package insert. New scientific techniques have allowed researchers to predict some drug interactions before they have been documented in people. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. The number of new drugs approved for marketing increases the chance of drug interactions, and new drug interactions are being identified with old drugs. Be vigilant. Make sure to tell your doctor and pharmacist the drugs you are taking and tell your doctor if you are taking any of these interacting drugs:

People who take monoamine oxidase inhibitors should be off these drugs for 14 days before starting fentanyl. These include: deprenyl, ELDEPRYL, furazolidone, FUROXONE, isocarboxazid, MARPLAN, MATULANE, NARDIL, PARNATE, phenelzine, procarbazine, selegiline, tranylcypromine.

Central nervous system (CNS) depressant drugs, including alcohol, antidepressants, antihistamines, antipsychotics, some blood pressure medications (reserpine, methyldopa, beta-blockers), motion sickness medications, muscle relaxants, narcotics sedatives, sleeping pills, and tranquilizers. Doses of fentanyl and any of these drugs may need to be lowered by 50%. If any of these drugs are discontinued while you use fentanyl, adjustments in doses may be required.

Other drugs that can interact with fentanyl are: carbamazepine, DILANTIN, EES, erythromycin, ketoconazole, MERIDIA, naltrexone, NIZORAL, NORVIR, phenytoin, REVIA, RIFADIN, rifampin, ritonavir, sibutramine, TEGRETOL.

Adverse Effects:

Call your doctor immediately if you experience:

• abdominal swelling
• difficulty breathing (If you care for a person who uses fentanyl patches and their breathing slows while sleeping, try to waken them. If breathing does not improve once awake, call their doctor.)⁵
• fainting
• problems speaking
• chest pain
• slow, fast, pounding, or irregular heartbeat
• confusion
• dizziness, incoordination, or fainting
• fever with or without chills (your dose may be lowered temporarily)⁵
• hallucinations
• restlessness or nervousness
• cold, red, swollen, or blistered skin with or without itching at patch
• thickened or scaly skin
• fluid-filled blisters
• spitting blood
• combative and/or suspicious thoughts
• difficulty urinating (decreased frequency and/or volume)
• mental or mood changes
• unusual bruising
• swollen glands
• any change in vision
• bladder pain

Call your doctor if these symptoms continue:

• decreased appetite
• anxiety, confusion
• constipation
• diarrhea
• dizziness
• unusual dreams
• memory loss
• drowsiness
• dry mouth
• headache
• blurred vision
• nausea or vomiting
• red or itchy skin, sweating, tingling or burning sensation
• weakness
• abdominal or stomach pain
• indigestion, gas
• weight loss
• sweating

Call your doctor if these symptoms continue after you stop taking this drug:

• diarrhea
• body aches
• increased heartbeat
• nervousness, restlessness, or irritability
• nausea or vomiting
• unusually enlarged pupils
• shivering or trembling
• increased sweating
• fever, runny nose, or sneezing
• stomach cramps
• trouble sleeping
• weakness
• increased yawning
• loss of appetite

Periodic Tests:

Ask your doctor which of these tests should be done periodically while you are taking this drug:

• blood pressure
• heart rate
• respiratory rate
• degree of sedation

In the end, while fentanyl is an effective pain reliever, it has been associated with some very serious side effects and its extremely high potency makes it a very dangerous drug when misused. An overdose of fentanyl can have deadly consequences in a matter of minutes.