Fentanyl Buccal Tablets

General

Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g., driving a car or operating machinery). Patients taking Fentanyl Buccal Tablets should be warned of these dangers and should be counseled accordingly.

The use of concomitant CNS active drugs requires special patient care and observation. (See WARNINGS.)

Chronic Pulmonary Disease

Because potent opioids can cause respiratory depression, Fentanyl Buccal Tablets should be titrated with caution in patients with chronic obstructive pulmonary disease or pre-existing medical conditions predisposing them to respiratory depression. In such patients, even normal therapeutic doses of Fentanyl Buccal Tablets may further decrease respiratory drive to the point of respiratory failure.

Head Injuries and Increased Intracranial Pressure

Fentanyl Buccal Tablets should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention such as those with evidence of increased intracranial pressure or impaired consciousness. Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.

Application Site Reactions

In clinical trials, 10% of all patients exposed to Fentanyl Buccal Tablets reported application site reactions. These reactions ranged from paresthesia to ulceration and bleeding. Application site reactions occurring in ≥ 1% of patients were pain (4%), ulcer (3%), and irritation (3%).

Application site reactions tended to occur early in treatment, were self-limited and only resulted in treatment discontinuation for 2% of patients.

Cardiac Disease

Intravenous fentanyl may produce bradycardia. Therefore, Fentanyl Buccal Tablets should be used with caution in patients with bradyarrhythmias.

Hepatic or Renal Disease

Insufficient information exists to make recommendations regarding the use of Fentanyl Buccal Tablets in patients with impaired renal or hepatic function.  Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. If the drug is used in these patients, it should be used with caution because of the hepatic metabolism and renal excretion of fentanyl.

Information for Patients and Caregivers

1. Patients and their caregivers must be instructed that children, especially small children, exposed to Fentanyl Buccal Tablets are at high risk of FATAL RESPIRATORY DEPRESSION. Patients and their caregivers must be instructed to keep Fentanyl Buccal Tablets out of the reach of children. (See SAFETY AND HANDLING, WARNINGS, and MEDICATION GUIDE for specific patient instructions.)

2. Patients and their caregivers must be provided a Medication Guide each time Fentanyl Buccal Tablets are dispensed because new information may be available.

3. Patients must be instructed not to take Fentanyl Buccal Tablets for acute pain, postoperative pain, pain from injuries, headache, migraine or any other short term pain, even if they have taken other opioid analgesics for these conditions.

4. Patients must be instructed on the meaning of opioid tolerance and that Fentanyl Buccal Tablets are only to be used as a supplemental pain medication for patients with pain requiring around-the-clock opioids, who have developed tolerance to the opioid medication, and who need additional opioid treatment of breakthrough pain episodes.

5. Patients must be instructed that, if they are not taking an opioid medication on a scheduled basis (around-the-clock), they should not take Fentanyl Buccal Tablets.

6. Patients should be instructed that the titration phase is the only period in which they may take more than ONE tablet to achieve a desired dose (e.g., two 100 mcg tablets for a 200 mcg dose).

7. Patients must be instructed that, if the breakthrough pain episode is not relieved after 30 minutes, they may take ONLY ONE ADDITIONAL DOSE OF Fentanyl Buccal Tablets USING THE SAME STRENGTH FOR THAT EPISODE. Thus, patients should take a maximum of two doses of Fentanyl Buccal Tablets for any breakthrough pain episode.

8. Patients must be instructed that they MUST wait at least 4 hours before treating another episode of breakthrough pain with Fentanyl Buccal Tablets.

9. Patients must be instructed NOT to share Fentanyl Buccal Tablets and that sharing Fentanyl Buccal Tablets with anyone else could result in the other individual’s death due to overdose.

10. Patients must be aware that Fentanyl Buccal Tablets contain fentanyl which is a strong pain medication similar to hydromorphone, methadone, morphine, oxycodone, and oxymorphone.

11. Patients must be instructed that the active ingredient in Fentanyl Buccal Tablets, fentanyl, is a drug that some people abuse. Fentanyl Buccal Tablets should be taken only by the patient they were prescribed for, and they should be protected from theft or misuse in the work or home environment.

12. Patients should be instructed that Fentanyl Buccal Tablets are not to be swallowed whole; this will reduce the effectiveness of the medication.  Tablets are to be placed between the cheek and gum above a molar tooth and allowed to dissolve.  After 30 minutes if remnants of the tablet still remain, patients may swallow it with a glass of water.

13. Patients must be cautioned to talk to their doctor if breakthrough pain is not alleviated or worsens after taking Fentanyl Buccal Tablets.

14. Patients must be instructed to use Fentanyl Buccal Tablets exactly as prescribed by their doctor and not to take Fentanyl Buccal Tablets more often than prescribed.

15. Patients must be cautioned that Fentanyl Buccal Tablets can affect a person’s ability to perform activities that require a high level of attention (such as driving or using heavy machinery).  Patients taking Fentanyl Buccal Tablets should be warned of these dangers and counseled accordingly.

16. Patients must be warned to not combine Fentanyl Buccal Tablets with alcohol, sleep aids, or tranquilizers except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.

17. Female patients must be informed that if they become pregnant or plan to become pregnant during treatment with Fentanyl Buccal Tablets, they should ask their doctor about the effects that Fentanyl Buccal Tablets (or any medicine) may have on them and their unborn children.

18. Patients and caregivers must be advised that if they have been receiving treatment with Fentanyl Buccal Tablets and the medicine is no longer needed they should flush any remaining product down the toilet, and if they then need further assistance, contact Watson at 1-866-510-7780.

Disposal of Unopened Fentanyl Buccal Tablets Blister Packages When No Longer Needed

Patients and members of their household must be advised to dispose of any unopened blister packages remaining from a prescription as soon as they are no longer needed.

To dispose of unused Fentanyl Buccal Tablets, remove Fentanyl Buccal Tablets from blister packages and flush down the toilet. Do not flush the Fentanyl Buccal Tablets blister packages or cartons down the toilet. (See SAFETY AND HANDLING.)

Detailed instructions for the proper storage, administration, disposal, and important instructions for managing an overdose of Fentanyl Buccal Tablets are provided in the Fentanyl Buccal Tablets Medication Guide. Patients should be encouraged to read this information in its entirety and be given an opportunity to have their questions answered.

In the event that a caregiver requires additional assistance in disposing of excess unusable tablets that remain in the home after a patient has expired, they should be instructed to call the Watson toll-free number (1-866-510-7780) or seek assistance from their local DEA office.

Laboratory Tests

The effects of Fentanyl Buccal Tablets on laboratory tests have not been evaluated.

Drug Interactions

See WARNINGS.

Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4); therefore potential interactions may occur when Fentanyl Buccal Tablets are given concurrently with agents that affect CYP3A4 activity. The concomitant use of Fentanyl Buccal Tablets with strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazadone) or moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug effects including fatal respiratory depression. Patients receiving Fentanyl Buccal Tablets concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time. Dosage increase should be done conservatively. (See PHARMACOKINETICS, Drug Interactions and DOSAGE AND ADMINISTRATION.)

Grapefruit and grapefruit juice decrease CYP3A4 activity, increasing blood concentrations of fentanyl, thus should be avoided.

Drugs that induce cytochrome P450 3A4 activity may have the opposite effects.

Concomitant use of Fentanyl Buccal Tablets with an MAO inhibitor, or within 14 days of discontinuation, is not recommended.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of fentanyl.

Fentanyl citrate was not mutagenic in the in vitro Ames reverse mutation assay in S. tymphimurium or E. coli, or the mouse lymphoma mutagenesis assay. Fentanyl citrate was not clastogenic in the in vivo mouse micronucleus assay.

Fentanyl impairs fertility in rats at doses of 30 mcg/kg IV and 160 mcg/kg SC. Conversion to human equivalent doses indicates this is within the range of the human recommended dosing for Fentanyl Buccal Tablets.

Pregnancy-Category C

There are no adequate and well-controlled studies in pregnant women. Fentanyl Buccal Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. No epidemiological studies of congenital anomalies in infants born to women treated with fentanyl during pregnancy have been reported.

Chronic maternal treatment with fentanyl during pregnancy has been associated with transient respiratory depression, behavioral changes, or seizures characteristic of neonatal abstinence syndrome in newborn infants. Symptoms of neonatal respiratory or neurological depression were no more frequent than expected in most studies of infants born to women treated acutely during labor with intravenous or epidural fentanyl. Transient neonatal muscular rigidity has been observed in infants whose mothers were treated with intravenous fentanyl.

Fentanyl is embryocidal as evidenced by increased resorptions in pregnant rats at doses of 30 mcg/kg IV or 160 mcg/kg SC. Conversion to human equivalent doses indicates this is within the range of the human recommended dosing for Fentanyl Buccal Tablets.

Fentanyl citrate was not teratogenic when administered to pregnant animals. Published studies demonstrated that administration of fentanyl (10, 100, or 500 mcg/kg/day) to pregnant rats from day 7 to 21, of their 21 day gestation, via implanted microosmotic minipumps was not teratogenic (the high dose was approximately 3-times the human dose of 1600 mcg per pain episode on a mg/m2 basis). Intravenous administration of fentanyl (10 or 30 mcg/kg) to pregnant female rats from gestation day 6 to 18, was embryo or fetal toxic, and caused a slightly increased mean delivery time in the 30 mcg/kg/day group, but was not teratogenic.

Labor and Delivery

Fentanyl readily passes across the placenta to the fetus; therefore Fentanyl Buccal Tablets are not recommended for analgesia during labor and delivery.

Nursing Mothers

Fentanyl is excreted in human milk; therefore Fentanyl Buccal Tablets should not be used in nursing women because of the possibility of sedation and/or respiratory depression in their infants. Symptoms of opioid withdrawal may occur in infants at the cessation of nursing by women using Fentanyl Buccal Tablets.

Pediatric Use

See WARNINGS.

Geriatric Use

Of the 304 patients with cancer in clinical studies of Fentanyl Buccal Tablets, 69 (23%) were 65 years of age and older.

Patients over the age of 65 years tended to titrate to slightly lower doses than younger patients.

Patients over the age of 65 years reported a slightly higher frequency for some adverse events specifically vomiting, constipation, and abdominal pain.  Therefore, caution should be exercised in individually titrating Fentanyl Buccal Tablets in elderly patients to provide adequate efficacy while minimizing risk.