FENTORA Tablet Ref.[10810] Active ingredients: Fentanyl

2.1 Important Dosage and Administration Instructions

• Healthcare professionals who prescribe FENTORA on an outpatient basis must enroll in the TIRF REMS Access program and comply with the requirements of the REMS to ensure safe use of FENTORA [see Warnings and Precautions (5.7)].
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].
• It is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose.
• Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.6)].
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with FENTORA and adjust the dosage accordingly [see Warnings and Precautions (5.1)].
• Instruct patients and caregivers to take steps to store FENTORA securely and to properly dispose of unused FENTORA as soon as no longer needed [see Warnings and Precautions (5.2, 5.6), Patient Counseling Information (17)].
• FENTORA is not bioequivalent with other fentanyl products. Do not convert patients on a mcg per mcg basis from other fentanyl products. There are no conversion directions available for patients on any other fentanyl products other than ACTIQ (Note: This includes oral, transdermal, or parenteral formulations of fentanyl.) [see Warnings and Precautions (5.5)].
• FENTORA is NOT a generic version of any other transmucosal fentanyl product [see Warnings and Precautions (5.5)].

2.2 Initial Dosage

The initial dose of FENTORA is always 100 mcg with the only exception being patients already using ACTIQ.

Patients on ACTIQ:

a. For patients being converted from ACTIQ, prescribers must use the Initial Dosing Recommendations for Patients on ACTIQ table below (Table 1). The doses of FENTORA in this table are starting doses and not intended to represent equianalgesic doses to ACTIQ. Patients must be instructed to stop the use of ACTIQ and dispose of any remaining units.

Table 1. Initial Dosing Recommendations for Patients on ACTIQ:

^* From this initial dose, titrate patient to effective dose.

b. For patients converting from ACTIQ doses equal to or greater than 600 mcg, titration should be initiated with the 200 mcg FENTORA tablet and should proceed using multiples of this tablet strength.

Repeat Dosing:

• In cases where the breakthrough pain episode is not relieved after 30 minutes, patients may take ONLY ONE additional dose using the same strength for that episode. Thus patients should take a maximum of two doses of FENTORA for any episode of breakthrough pain.
• Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with FENTORA.

2.3 Dose Titration

• From an initial dose, closely follow patients and change the dosage strength until the patient reaches a dose that provides adequate analgesia with tolerable side effects. Patients should record their use of FENTORA over several episodes of breakthrough pain and discuss their experience with their healthcare provider to determine if a dosage adjustment is warranted.
• Patients whose initial dose is 100 mcg and who need to titrate to a higher dose, can be instructed to use two 100 mcg tablets (one on each side of the mouth in the buccal cavity) with their next breakthrough pain episode. If this dosage is not successful, the patient may be instructed to place two 100 mcg tablets on each side of the mouth in the buccal cavity (total of four 100 mcg tablets). Titrate using multiples of the 200 mcg FENTORA tablet for doses above 400 mcg (600 mcg and 800 mcg). Note: Do not use more than 4 tablets simultaneously.
• In cases where the breakthrough pain episode is not relieved after 30 minutes, patients may take ONLY ONE additional dose of the same strength for that episode. Thus patients should take a maximum of two doses of FENTORA for any breakthrough pain episode. During titration, one dose of FENTORA may include administration of 1 to 4 tablets of the same dosage strength (100 mcg or 200 mcg).
• Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with FENTORA. To reduce the risk of overdose during titration, patients should have only one strength of FENTORA tablets available at any time.
• Patients should be strongly encouraged to use all of their FENTORA tablets of one strength prior to being prescribed the next strength. If this is not practical, unused FENTORA should be disposed of safely [see How Supplied/Storage and Handling (16)]. Dispose of any unopened FENTORA tablets remaining from a prescription as soon as they are no longer needed.

2.4 Maintenance Dosing

• Once titrated to an effective dose, patients should generally use only ONE FENTORA tablet of the appropriate strength per breakthrough pain episode.
• On occasion when the breakthrough pain episode is not relieved after 30 minutes, patients may take ONLY ONE additional dose using the same strength for that episode.
• Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with FENTORA.
• Dosage adjustment of FENTORA may be required in some patients.

Generally, the FENTORA dose should be increased only when a single administration of the current dose fails to adequately treat the breakthrough pain episode for several consecutive episodes.

e. If the patient experiences greater than four breakthrough pain episodes per day, the dose of the around-the-clock opioid used for persistent pain should be re-evaluated.

f. Once an effective dose is determined using the titration scheme outlined above, an alternate route of administration is sublingual (placing the tablet under the tongue).

2.5 Administration of FENTORA

Opening the Blister Package:

• Instruct patients not to open the blister until ready to administer FENTORA.
• Separate a single blister unit from the blister card by bending and tearing apart at the perforations.
• Bend the blister unit along the line where indicated.
• Peel back the blister backing to expose the tablet. Patients should NOT attempt to push the tablet through the blister as this may cause damage to the tablet.
• Do not store the tablet once it has been removed from the blister package as the tablet integrity may be compromised and, more importantly, because this increases the risk of accidental exposure to the tablet.

Tablet Administration:

Once the tablet is removed from the blister unit, the patient should immediately place the entire FENTORA tablet in the buccal cavity (above a rear molar, between the upper cheek and gum) or place the entire FENTORA tablet under the tongue. Patients should not split the tablet.

The FENTORA tablet should not be crushed, sucked, chewed or swallowed whole, as this will result in lower plasma concentrations than when taken as directed.

The FENTORA tablet should be left between the cheek and gum or under the tongue until it has disintegrated, which usually takes approximately 14-25 minutes.

After 30 minutes, if remnants from the FENTORA tablet remain, they may be swallowed with a glass of water.

It is recommended that patients alternate sides of the mouth when administering subsequent doses of FENTORA in the buccal cavity.

2.6 Discontinuation of FENTORA

For patients no longer requiring opioid therapy, consider discontinuing FENTORA along with a gradual downward tapering (titration) of other opioids to minimize possible withdrawal effects. In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, FENTORA therapy can usually be discontinued immediately. [see Drug Abuse and Dependence (9.3)]

2.7 Disposal of FENTORA

To dispose of unused FENTORA, remove FENTORA tablets from blister packages and flush down the toilet. Do not flush FENTORA blister packages or cartons down the toilet. If you need additional assistance with disposal of FENTORA, call Teva Pharmaceuticals at 1-888-483-8279.

Clinical Presentation

Acute overdose with FENTORA can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2)].

Treatment of Overdose

In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to fentanyl overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to fentanyl overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of fentanyl in FENTORA, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Store at 20 to 25°C (68 to 77°F) with excursions permitted between 15° and 30°C (59° to 86°F) until ready to use. (See USP Controlled Room Temperature.)

Protect FENTORA from freezing and moisture. Do not use if the blister package has been tampered with.

Store FENTORA securely and dispose of properly [see Patient Counseling Information (17)].