Pronunciation:

FEN-ta-nil SIT-rate

Brand Names:

• Actiq
• Fentora

Dosage Forms:

• Lozenge/Troche
• Tablet

Warnings:

• FENTANYL CITRATE (OTFC)
  • Physicians and other healthcare providers must become familiar with the important warnings in this label.
  • Oral Transmucosal fentanyl citrate (OTFC) is indicated only for the management of breakthrough cancer pain in patients with malignancies who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
  • Because life-threatening hypoventilation could occur at any dose in patients not taking chronic opiates, OTFC is contraindicated in the management of acute or postoperative pain. This product must not be used in opioid non-tolerant patients.
  • OTFC is intended to be used only in the care of cancer patients and only by oncologists and pain specialists who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.
  • Patients and their caregivers must be instructed that OTFC contains a medicine in an amount which can be fatal to a child. Patients and their caregivers must be instructed to keep all units out of the reach of children and to discard opened units properly .

• ACTIQ(R)
  • Must not be used in opioid non-tolerant patients.
  • Contains fentanyl, a Schedule II controlled substance with abuse liability similar to other opioid analgesics.
  • Life-threatening hypoventilation could occur at any dose in patients not taking chronic opiates.
  • Contraindicated in management of acute or postoperative pain.
  • Contains medicine in an amount that can be fatal to a child. Keep out of reach of children and discard opened units properly.
  • Use with strong and moderate CYP450 3A4 inhibitors may result in potentially fatal respiratory depression.
  • ACTIQ(R) contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. ACTIQ(R) can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ACTIQ(R) in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
  • ACTIQ(R) is indicated only for the management of breakthrough cancer pain in patients with malignancies who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
  • ACTIQ(R) is intended to be used only in the care of cancer patients and only by oncologists and pain specialists who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.
  • Because life-threatening hypoventilation could occur at any dose in patients not taking chronic opiates, ACTIQ(R) is contraindicated in the management of acute or postoperative pain. This product must not be used in opioid non-tolerant patients.
  • Patients and their caregivers must be instructed that ACTIQ(R) contains a medicine in an amount which can be fatal to a child. All units must be kept out of the reach of children and opened units properly discarded.
  • The concomitant use of ACTIQ(R) with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression .

Only indicated in patients who are already receiving and who are tolerant to opioid therapy. Life-threatening hypoventilation can occur at any dose in patients not taking chronic opiates. Contraindicated in the management of acute or postoperative pain. Has an abuse liability similar to other opioid analgesics. Contains a medicine in an amount which can be fatal to a child. Do not substitute FENTORA(R) on a mcg per mcg basis when converting patients from other oral fentanyl products due to the higher bioavailability of fentanyl in FENTORA(R). Use of ACTIQ(R) with strong and moderate CYP3A4 inhibitors may result in potentially fatal respiratory depression .

• FENTORA(R)
  • Reports of serious adverse events, including deaths in patients treated with FENTORA(R) have been reported. Deaths occurred as a result of improper patient selection (eg, use in opioid non-tolerant patients) and/or improper dosing. The substitution of FENTORA(R) for any other fentanyl product may result in fatal overdose.
  • FENTORA(R) is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid tolerant are those who are taking around-the-clock medicine consisting of at least 60 mg of oral morphine daily, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
  • FENTORA(R) is not indicated for use in opioid non-tolerant patients including those with only as needed (PRN) prior exposure.
  • FENTORA(R) is contraindicated in the management of acute or postoperative pain including headache/migraine. Life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid nontolerant patients.
  • When prescribing, do not convert patients on a mcg per mcg basis from transmucosal fentanyl citrate lozenge (ACTIQ(R)) to FENTORA(R). Carefully consult the Initial Dosing Recommendations table.
  • When dispensing, do not substitute a FENTORA(R) prescription for other fentanyl products. Substantial differences exist in the pharmacokinetic profile of FENTORA(R) compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl. As a result of these differences, the substitution of FENTORA(R) for any other fentanyl product may result in fatal overdose.
  • Special care must be used when dosing FENTORA(R). If the breakthrough pain episode is not relieved after 30 minutes, patients may take ONLY one additional dose using the same strength and must wait at least 4 hours before taking another dose.
  • FENTORA(R) contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. FENTORA(R) can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing FENTORA(R) in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
  • Patients and their caregivers must be instructed that FENTORA(R) contains a medicine in an amount which can be fatal to a child. Patients and their caregivers must be instructed to keep all tablets out of the reach of children.
  • FENTORA(R) is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.
  • The concomitant use of FENTORA(R) with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression .

Only indicated for treatment of cancer pain in patients who are already receiving and who are tolerant to opioid therapy. Life-threatening hypoventilation can occur at any dose in patients not taking chronic opiates. Contraindicated in the management of acute or postoperative pain. Has an abuse liability similar to other opioid analgesics. Contains a medicine in an amount which can be fatal to a child. Do not substitute FENTORA(R) on a mcg per mcg basis when converting patients from other oral fentanyl products due to the higher bioavailability of fentanyl in FENTORA(R). Use of FENTORA(R) with strong and moderate CYP3A4 inhibitors may result in potentially fatal respiratory depression .

Classifications:

Therapeutic—

Analgesic

Chemical—

Fentanyl

Uses of This Medicine:

Fentanyl belongs to the group of medicines called narcotic analgesics, which are medicines used to relieve pain. The oral transmucosal or buccal form of fentanyl is used to treat breakthrough cancer pain. Breakthrough episodes of cancer pain are the flares of pain which “breaks through” the medication used to control the persistent pain. Oral transmucosal or buccal fentanyl is only used in patients who are already taking narcotic analgesics .

Fentanyl acts in the central nervous system (CNS) to relieve pain. Some of its side effects are also caused by actions in the CNS. When a narcotic is used for a long time, it may become habit-forming (causing mental or physical dependence). However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by reducing the dose gradually over a period of time before treatment is stopped completely. Your doctor will take this into consideration when deciding on the amount of oral transmucosal or buccal fentanyl you should receive .

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of buccal fentanyl in children below 18 years of age, or oral transmucosal fentanyl in children below 16 years of age. Safety and efficacy have not been established in these age groups .

Older adults—

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of oral transmucosal or buccal fentanyl in the elderly. However, elderly patients may be more sensitive to the effects of narcotic analgesics than younger adults and are more likely to have age-related kidney disease, which may require adjustment of dosage in patients receiving oral transmucosal or buccal fentanyl .

Pregnancy—

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast-feeding—

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Other medicines—

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Naltrexone

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse or history of or
• Drug dependence, especially narcotic abuse or dependence, history of or
• Kidney disease or
• Liver disease—The chance of side effects may be increased.

• Diabetes—Use with caution. Oral transmucosal fentanyl contains sugar .

• Emphysema or other chronic lung disease or
• Head injuries—Some of the side effects of oral transmucosal or buccal fentanyl can cause serious problems in people who have these medical problems .

• Slow heartbeat or other heart problems—Oral transmucosal or buccal fentanyl can make this condition worse .

Proper Use of This Medicine:

Oral transmucosal or buccal fentanyl comes with patient instructions. If you are switching from the oral transmucosal form of fentanyl to buccal form, make sure you read the patient instruction carefully. These forms are very different .

• Keep medication in sealed pouch until ready to use.
• The foil package should be opened with scissors immediately prior to product use.
• Place the medicine in mouth between the cheek and lower gum, occasionally moving the medicine from one side to the other using the handle.
• The medicine should be sucked, not chewed.
• Suck the medicine over a 15-minute period .

• Keep medication in sealed pouch until ready to use.
• Remove the tablet from the blister unit just before product use. Do not push the tablet through the blister as this may cause damage to the tablet.
• Do not store the tablet after removing it from the blister package. It should be used immediately.
• Place the medicine in your mouth between the upper cheek and gum, above a back molar.
• Allow the tablet to dissolve. It usually takes around 14 to 25 minutes for the tablet to dissolve completely.
• Do not suck, chew, or swallow the tablet. If the tablet did not dissolve completely after 30 minutes, you may swallow it with a glass of water .

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For cancer pain:
  • For oral transmucosal dosage form:
    • Adults—At first, 200 micrograms (mcg) during an episode of breakthrough cancer pain. Redosing may start 15 minutes after the previous dose has been completed (30 minutes after the start of the previous dose). Patients should not use more than 2 units per episode of breakthrough pain. Patients should record their use over several episodes of breakthrough cancer pain and review their experience with their physicians to determine if a dosage adjustment is warranted.
    • Children—Use and dose must be determined by the doctor .
  • For buccal dosage form (tablets):
    • Adults—At first, 100 mcg during an episode of breakthrough cancer pain. Dosing may be repeated if pain is not relieved by a single dose. Redosing may start 30 minutes after taking this medicine and the same dosage strength should be used. Your doctor may increase your dose as needed. Patients should not use more than 4 tablets per episode of breakthrough pain. Patients should record their use over several episodes of breakthrough cancer pain and review their experience with their doctor to determine if a dosage adjustment is warranted.
    • Children—Use and dose must be determined by the doctor .

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Do not use if the foil pouch has been opened. A temporary storage bottle is provided as part of the Actiq [reg] Welcome Kit. This container is to be used by patients or their caregivers in the event that a partially consumed unit cannot be disposed of promptly. If additional assistance is required, refer to 1-800-615-0187.

Dispose of any unopened buccal fentanyl tablets that are no longer needed. To dispose, remove the buccal fentanyl tablets from the blister packages and flush down the toilet. Do not flush the blister packages or cartons down the toilet. If additional assistance is required, call 1-800-896-5855 .

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to check you for any problems or unwanted effects that may be caused by this medicine .

Oral transmucosal or buccal fentanyl contains a medicine in an amount which can be fatal to a child. Patients and their caregivers should keep oral transmucosal or buccal fentanyl out of the reach of children and discard open units properly .

This medicine will add to the effects of alcohol and other CNS depressants (medicines that can make you drowsy or 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; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the other medicines listed above while you are using this medicine.

Oral transmucosal or buccal fentanyl may cause some people to become drowsy, dizzy, or lightheaded, or to feel a false sense of well-being. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert and clearheaded. 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.

Using narcotics for a long time can 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.

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 oral transmucosal or buccal fentanyl .

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 reduce gradually the amount you are using before stopping treatment completely to lessen the chance of withdrawal side effects.

Using too much oral transmucosal or buccal fentanyl, or taking too much of another narcotic while using oral transmucosal or buccal fentanyl, 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 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 .

Check with your dentist at regular times while using fentanyl. This medicine contains sugar and may increase your chance for tooth decay or other trouble with your teeth or gums.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions .

Side Effects of This Medicine:

Along with its needed effects, a medicine 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 as soon as possible if any of the following side effects occur:

More common

Black, tarry, stools

blurred vision

chest pain

confusion

convulsions

cough

decreased urine

difficult or labored breathing

dizziness

dry mouth

fainting

fever or chills

increased thirst

irregular heartbeat

lightheadedness

loss of appetite

lower back or side pain

mood changes

muscle pain or cramps

nausea or vomiting

nervousness

numbness or tingling in hands, feet, or lips

painful or difficult urination

pale skin

pounding in the ears

rapid breathing

shortness of breath

sneezing

sore throat

sunken eyes

swelling of hands, ankles, feet, or lower legs

tightness in chest

troubled breathing with exertion

ulcers, sores, or white spots in mouth

unusual bleeding or bruising

unusual tiredness or weakness

wheezing

wrinkled skin

Less common

Abdominal pain

change in walking and balance

clumsiness or unsteadiness

decreased awareness or responsiveness

decreased frequency of urination

headache

muscle twitching or jerking

pounding in the ears

rhythmic movement of muscles

seeing, hearing, or feeling things that are not there

seizures

severe constipation

severe sleepiness

shakiness in legs, arms, hands, feet

slow or fast heartbeat

thinking abnormalities

trembling or shaking of hands or feet

Symptoms of overdose

Extremely shallow or slow breathing

Some side effects 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

Back pain

diarrhea

difficulty having a bowel movement (stool)

difficulty in moving

discouragement

feeling sad or empty

irritability

lack or loss of strength

loss of interest or pleasure

muscle stiffness

pain in joints

sleepiness or unusual drowsiness

sleeplessness

tiredness

trouble concentrating

trouble sleeping

unable to sleep

weight loss

Less common

Changes in vision

excessive muscle tone

feeling of constant movement of self or surroundings

feeling of warmth or heat

flushing or redness of skin, especially on face and neck

irritation, pain, or sores at site of application

itching skin

muscle tension or tightness

rash

sensation of spinning

sweating

Incidence not known

Tooth pain

trouble with gums

trouble with teeth

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

Restlessness

speech disorder

stomach cramps

weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.