"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
SUBSYS is indicated for the management of breakthrough pain in adult cancer patients who are already receiving and who are tolerant to around-the-clock 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 oral oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids when taking SUBSYS.
This product must not be used in opioid non-tolerant patients because life-threatening respiratory depression and death could occur at any dose in patients not on a chronic regimen of opioids. For this reason, SUBSYS is contraindicated in the management of acute or postoperative pain.
SUBSYS 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.
Limitations of Use
As part of the Transmucosal Immediate-Release Fentanyl (TIRF) REMS ACCESS Program, SUBSYS may be dispensed only to outpatients enrolled in the program. [see WARNINGS AND PRECAUTIONS]. For inpatient administration (e.g. hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of SUBSYS, patient enrollment is not required.
DOSAGE AND ADMINISTRATION
Healthcare professionals who prescribe SUBSYS 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 SUBSYS. [see WARNINGS AND PRECAUTIONS]
As with all opioids, the safety of patients using such products is dependent on health care professionals prescribing them in strict conformity with their approved labeling with respect to patient selection, dosing, and proper conditions for use.
SUBSYS 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.)
Patients on Actiq
The initial dose of SUBSYS is always 100 mcg with the only exception of patients already using Actiq.
a. For patients being converted from Actiq, prescribers must use the Initial Dosing Recommendations for Patients on Actiq table below (Table 1). Patients must be instructed to stop the use of Actiq and dispose of any remaining units.
Table 1: Initial Dosing Recommendations for Patients
|Current ACTIQ Dose (mcg)||Initial SUBSYS Dose (mcg)|
|200||100 mcg spray|
|400||100 mcg spray|
|600||200 mcg spray|
|800||200 mcg spray|
|1200||400 mcg spray|
|1600||400 mcg spray|
b. For patients converting from Actiq doses 400 mcg and below, titration should be initiated with 100 mcg SUBSYS and should proceed using multiples of this strength.
c. For patients converting from Actiq doses of 600 and 800 mcg, titration should be initiated with 200 mcg SUBSYS and should proceed using multiples of this strength.
d. For patients converting from Actiq doses of 1200 and 1600 mcg, titration should be initiated with 400 mcg SUBSYS and should proceed using multiples of this strength.
All Other Patients
Individually titrate SUBSYS to a dose that provides adequate analgesia and minimizes side effects. The initial dose of SUBSYS to treat episodes of breakthrough cancer pain is always 100 mcg. When prescribing, do not switch patients on a mcg per mcg basis from any other oral transmucosal fentanyl product to SUBSYS as SUBSYS is not equivalent on a mcg per mcg basis with any other fentanyl product [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Prescribe an initial titration supply of 100 mcg SUBSYS units, which limits the number of units in the home during titration.
Avoid prescribing a higher dose until patients have used up all units to prevent confusion and possible overdose.
- From the 100 mcg initial dose, closely follow patients and change the dosage level until the patient reaches a dose that provides adequate analgesia using a single SUBSYS dose per breakthrough cancer pain episode with tolerable side effects. Patients should record their use of SUBSYS over several episodes of breakthrough cancer pain and review their experience with their physicians to determine if a dosage adjustment is warranted.
- For each breakthrough pain episode treated, if pain 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 SUBSYS for any breakthrough pain episode.
- Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with SUBSYS.
- If there is a need to titrate to a 200 mcg dose, prescribe 200 mcg SUBSYS units.
- Subsequent titration steps are 400 mcg, 600 mcg, 800 mcg, 1200 mcg and 1600 mcg. See Table 1.
- To reduce the risk of overdose during titration, patients should have only one strength of SUBSYS available at any time.
Table 1: Titration Steps
|100 mcg||1 x 100 mcg unit|
|200 mcg||1 x 200 mcg unit|
|400 mcg||1 x 400 mcg unit|
|600 mcg||1 x 600 mcg unit|
|800 mcg||1 x 800 mcg unit|
|1200 mcg||2 x 600 mcg unit|
|1600 mcg||2 x 800 mcg unit|
SUBSYS Titration Process
Once titrated to a dose that provides adequate pain relief and tolerable side effects, patients should generally use ONLY ONE SUBSYS dose of the appropriate strength per breakthrough pain episode.
On those occasions when the breakthrough pain episode is not relieved within 30 minutes after administration of the SUBSYS dose, the patient 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 SUBSYS. Once a successful dose has been found, patients should limit consumption to four or fewer doses per day.
Dosage adjustment of SUBSYS may be required in some patients in order to continue to provide adequate relief of breakthrough pain.
If signs of excessive opioid effects appear following administration of a single SUBSYS dose, subsequent doses should be decreased.
Generally, only increase the SUBSYS dose when a single administration of the current dose fails to adequately treat the breakthrough pain episode for several consecutive episodes.
If the patient experiences greater than four breakthrough pain episodes per day, the dose of the maintenance (around-theclock) opioid used for persistent pain should be re-evaluated. In addition, if pain worsens, re-evaluate the patient for changes in the underlying pain condition.
Administration of SUBSYS
The blister package should be opened with scissors immediately prior to product use. The patient should carefully spray the contents of the unit into his or her mouth underneath the tongue.
Disposal of SUBSYS
Patients and caregivers must be advised to dispose of used unit dose systems immediately after use and any unneeded unit dose systems remaining from a prescription as soon as they are no longer needed. Consumed units represent a special risk because they are no longer protected by the child resistant blister package, yet may contain enough medicine to be fatal to a child. [see PATIENT INFORMATION]
A disposal bottle is provided with every carton dispensed. This container is to be used by patients or their caregivers to dispose of the contents of any unneeded unit dose systems when they are no longer needed. Instructions for usage of the disposal bottle are included in the Medication Guide and Instructions for Use.
In cancer patients with mucositis, exposure to SUBSYS was greater than in patients without mucositis. For patients with Grade 1 mucositis, the increased maximum serum concentration and overall exposure requires closer monitoring for respiratory depression and central nervous system depression, particularly during initiation of therapy with SUBSYS. For patients with Grade 2 mucositis or higher, avoid use of SUBSYS unless the benefits outweigh the potential risk of respiratory depression from increased exposure. [see CLINICAL PHARMACOLOGY]
Dosage Forms And Strengths
SUBSYS is a sublingual spray available in 100 mcg, 200 mcg, 400 mcg, 600 mcg, and 800 mcg strengths [see Storage and Handling].
Storage And Handling
SUBSYS is supplied in individually sealed blister packages. Store at 20-25°C (68-77°F) with excursions permitted between 15° and 30°C (59° to 86°F) until ready to use. [See USP Controlled Room Temperature.] Do not use if the blister package has been opened.
Disposal of SUBSYS
Patients and caregivers must be advised to dispose of used unit doses systems immediately after use and any unneeded unit dose systems remaining from a prescription as soon as they are no longer needed. Consumed units represent a special risk because they are no longer protected by the blister package, yet may contain enough medicine to be fatal to a child. [see PATIENT INFORMATION].
A disposal bottle is provided with every carton dispensed. [see PATIENT INFORMATION]. This container is to be used by patients or their caregivers to dispose of the contents of any unneeded unit dose systems when they are no longer needed. Instructions for usage of the disposal bottle are included in the Medication Guide.
Patients and members of their household must be advised to dispose of any units remaining from a prescription as soon as they are no longer needed.
Instructions for disposal are also included in Disposal of Used SUBSYS Unit Dose Systems and Disposal of Unopened SUBSYS Unit Dose Systems When No Longer Needed (17.4) and in the Medication Guide. If additional assistance is required, call Insys Therapeutics, Inc. at 1-877-978-2797.
Each SUBSYS carton contains individual blister packages containing spray units of SUBSYS, a supply of small white disposal bags for disposing of used SUBSYS units, a Medication Guide and a Package Insert. In addition to your supply of SUBSYS spray units, you will be given a separate carton containing a disposal bottle, a large disposal bag, and a Medication Guide.
SUBSYS is supplied in individually sealed, protective blister packages. These blister packages are packed into 10 and 30 per shelf cartons.
Each unit dose system consists of a white actuator attached to a light purple vial holder. The dosage strength is marked on the label on the actuator, the blister package and the shelf carton. See the protective blister package and shelf carton for product information.
|Dosage Strength (fentanyl base)||Carton/Blister Package Color||NDC Number|
|400 mcg||Magenta (Pink)||20482-004-10|
Note: Colors are a secondary aid in product identification. Please be sure to confirm the printed dosage before dispensing.
Manufactured by: DPT Laboratories, Ltd., Lakewood, NJ 08701. for: Insys Therapeutics, Inc., Phoenix, AZ 85044.
Last reviewed on RxList: 8/22/2013
This monograph has been modified to include the generic and brand name in many instances.
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