Important Safety Information for TIRFs
Selected Important Safety Information


TIRF medicines contain fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. TIRF medicines can be abused in a manner similar to other opioid agonists, legal or illicit. Consider the potential for abuse when prescribing or dispensing TIRF medicines 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.

Serious adverse events, including deaths, in patients treated with some oral transmucosal fentanyl medicines have been reported. Deaths occurred as a result of improper patient selection (e.g., use in opioid non-tolerant patients) and/or improper dosing. The substitution of a TIRF medicine for any other fentanyl medicine, including another TIRF medicine, may result in fatal overdose.

TIRF medicines are indicated only for the management of breakthrough pain in adult cancer patients 18 years of age and older (16 years of age and older for Actiq® brand and generic equivalents) 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:

  • at least 60 mg of oral morphine/daily
  • at least 25 mcg transdermal fentanyl/hour
  • at least 30 mg of oral oxycodone daily
  • at least 8 mg oral hydromorphone daily
  • at least 25 mg oral oxymorphone daily
  • or an equianalgesic dose of another opioid daily for a week or longer.

TIRF medicines are contraindicated in opioid non-tolerant patients and are contraindicated in the management of acute or postoperative pain, including headache/migraine and dental pain, or use in the emergency room. Please see the individual medicine prescribing information for a full list of specific situations in which TIRF medicines are not indicated or are contraindicated. Life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients. Deaths have occurred in opioid non-tolerant patients treated with some TIRF medicines.

When prescribing, do not convert patients on a mcg per mcg basis from another fentanyl medicine to a TIRF medicine, except for substitutions between a branded TIRF medicine and its generic equivalent. Patients beginning treatment with TIRF medicines must begin with titration from the lowest available dose for that specific medicine. Carefully consult the Initial Dosing Instructions in the TIRF medicine-specific Full Prescribing Information.

When dispensing, TIRF medicines are not interchangeable with each other, regardless of route of administration. Differences exist in the pharmacokinetics of TIRF medicines resulting in clinically important differences in the amount of fentanyl absorbed that could cause a fatal overdose. Converting patients from one TIRF medicine to a different TIRF medicine must not be done on a microgram-per-microgram basis, and must be titrated according to the labeled dosing instructions each time they begin use of a new TIRF medicine. The only exception is for substitution between a branded TIRF medicine and its specific generic equivalent.

Special care must be used when dosing TIRF medicines. Refer to the Full Prescribing Information for the individual TIRF medicine for guidance on the maximum number of doses that can be taken per breakthrough pain episode and the time that patients must wait before treating another episode of breakthrough pain with the TIRF medicine.

TIRF medicines are 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.

Patients and their caregivers must be instructed that TIRF medicines contain a medicine in an amount which can be fatal in children, in individuals for whom it is not prescribed, and in those who are not opioid-tolerant. All medicines must be kept out of the reach of children.

The concomitant use of TIRF medicines with cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.

Adverse Reactions

The most commonly observed adverse reactions with TIRF medicines include typical opioid adverse reactions, such as nausea, vomiting, constipation, somnolence, dizziness, and headache. Refer to individual medicine prescribing information for all adverse reactions. Expect opioid side effects and manage them accordingly.

Please see the individual Full Prescribing Information for each TIRF medicine for all information including boxed warnings, and Medication Guide for important safety information for each TIRF medicine.

Adverse Event Reporting

Promptly report suspected adverse events including misuse, abuse, addiction and overdoses directly to the TIRF REMS Access program at 1-866-822-1483. You also may report adverse event information to the FDA MedWatch Reporting System by telephone at 1-800-FDA-1088 or by mail using Form 3500, available at

Medication Guide

It is important that you discuss the risks of TIRF medicines with your patients and encourage them to read the relevant Medication Guide. The Medication Guide provides important information on the safe and effective use of TIRF medicine and you will need to review the appropriate Medication Guide for the TIRF medicines you prescribe to your patient. Patients should be counseled on the need to store TIRF medicines safely out of the reach of children and other persons for whom the medicine is not prescribed.

You must provide your patient with a copy of the appropriate Medication Guide for the TIRF medicine you prescribe. Medication Guides will be provided to you by the manufacturers of individual TIRF medicines. If you require additional Medication Guides you can:

  • Print copies from the TIRF REMS Access program website at
  • Contact the TIRF REMS Access program at 1-866-822-1483.

For assistance, please call the TIRF REMS Access program at 1-866-822-1483.



Copyright © INSYS Therapeutics, Inc., 2016 All Rights Reserved.

Before accessing the sites, please read the following terms and conditions carefully as they govern your use of the sites. If you do not agree with these terms and conditions, you are not granted permission by INSYS Therapeutics, Inc. to access or otherwise use the sites.,, AND User Agreements

Welcome to the,, and websites (also referred to as the "Sites") owned and operated by INSYS Therapeutics, Inc. ("INSYS Therapeutics, Inc."). This Agreement contains the terms, covenants, conditions, and provisions (the "Terms and Conditions") upon which you ("you") may access and use the Sites.

Terms and Conditions

By accessing, viewing, or using the Sites, you, the user, indicate that you understand and intend these Terms and Conditions to be the legal equivalent of a signed, written contract and equally binding, and that you accept such Terms and Conditions and agree to be legally bound by them. Please note that INSYS Therapeutics, Inc., reserves the right to change these Terms and Conditions. Your continued use of the Sites following such modifications will be conclusively deemed acceptance of any changes to these Terms and Conditions.

License Grant

This Agreement provides you with a personal, revocable, nonexclusive, nontransferable license to use the Sites conditioned on your continued compliance with the Terms and Conditions of this Agreement. You may print and download materials and information on the Sites solely for personal and noncommercial use, provided that all hard copies contain all copyright and other applicable notices contained in such materials and information. As a further condition of use of the Sites, you warrant to INSYS Therapeutics, Inc., that you will not use the Sites for any purpose that is unlawful or otherwise prohibited by these Terms and Conditions.

Intellectual Property Rights

All materials contained in the Site are protected by law, including but not limited to United States copyright, trade secret, and trademark law, as well as other state, national, and international laws and regulations. The contents of the Site, as well as all materials distributed in conjunction with the Site, are Copyright ©2016 INSYS Therapeutics, Inc. or its affiliates, licensors or suppliers. All rights reserved. INSYS Therapeutics, Inc., also owns a copyright in the Site as a collective work and/or compilation, and in the selection, coordination, arrangement, and enhancement of such content. Re-publication or citation of any other content generated by the Site without the written consent of INSYS Therapeutics, Inc., is expressly prohibited. You agree not to copy, modify, adapt, frame, mirror, reproduce, translate, distribute, transmit, reverse engineer, decompile, or disassemble any aspect of the Site, except as expressly allowed by this Agreement. All product names, whether or not appearing in large print, italics or with the trademark symbol, are trademarks of INSYS Therapeutics, Inc., its affiliates, related companies or its licensors or joint venture partners and any use of such marks without the express written permission of INSYS Therapeutics, Inc., is strictly prohibited. Unauthorized use of any material contained on the Sites may violate copyright laws, trademark laws, trade secret laws, the laws of privacy and publicity, and communications regulations and statutes. Please be aware that INSYS Therapeutics, Inc., actively and aggressively enforces its intellectual property rights to the fullest extent of the law.

Copyright Owners' Rights Under the Digital Millennium Copyright Act of 1998

The Digital Millennium Copyright Act of 1998 (the "DMCA") provides recourse for copyright owners who believe that material appearing on the Internet infringes their rights under US copyright law. If you believe, in good faith, that materials hosted by INSYS Therapeutics, Inc., infringe your copyright, you (or your agent) may send us a notice requesting that the materials be removed, or access to them blocked. If you believe, in good faith, that a notice of copyright infringement has been wrongly filed against you, the DMCA permits you to send us a counter-notice.

Notices and counter-notices must meet statutory requirements imposed by the DMCA. One place to find more information on the DMCA is the U.S. Copyright Office Web site. Notices and counter-notices for the Site should be sent to INSYS Therapeutics, Inc., Attn. General Counsel, 1333 S Spectrum Blvd #100, Chandler, AZ 85286.


INSYS Therapeutics, Inc., welcomes your feedback and suggestions about how to improve the Sites. Any ideas, suggestions, information, know-how, material, or other content (collectively, "content") received through the Sites, however, will be deemed to include a royalty-free, perpetual, irrevocable, transferable, worldwide, nonexclusive right and license for INSYS Therapeutics, Inc., to adopt, publish, reproduce, disseminate, transmit, distribute, copy, use, create derivative works, display, (in whole or part), or act on such content without additional approval or consideration, in any form, media, or technology now known or later developed for the full term of any rights that may exist in such content. Any communications or information that you send to INSYS Therapeutics, Inc., through the internet, electronic mail, post on our Site or otherwise, including questions, comments, suggestions or the like, are deemed to be non-confidential and INSYS Therapeutics, Inc., shall have no obligation with respect to such information.

Jurisdiction and Indemnification

The information provided on the Sites is intended for U.S. audiences and has been designed to comply with U.S. regulatory guidelines. These Terms of Use and your use of our Sites shall be governed by the laws of the United States and the State of Arizona without regard to conflict of law principles. By using our Sites, you agree that any legal action shall be brought exclusively in a federal or state court of competent jurisdiction sitting in the U.S. state of Arizona. If any provision of these Terms of Use is held to be unlawful or unenforceable, then such provision shall be severable without affecting the enforceability of all remaining provisions. By using any of our Sites, you agree to indemnify, defend and hold harmless INSYS Therapeutics, Inc., its officers, directors, employees, agents, and third-party affiliates from and against any and all losses, expenses, damages, and costs, including reasonable attorney's fees, resulting from any violation by you of these Terms of Use.


Medical information that appears on this website is for informational purposes only and is not, nor is intended to be, a medical diagnosis or a replacement for advice given by a physician or other medical professional. Any reliance on the information provided on this website is solely the responsibility of the individual. While INSYS Therapeutics, Inc., makes reasonable efforts to ensure the timeliness and accuracy of the materials present on this Web site, it makes no assurances or warranties (express or implied) as to the accuracy of the information provided on this website and shall not be liable for any direct, indirect, incidental, consequential or otherwise special damages or injuries resulting from the use of this website and reliance on the materials contained here. This limitation includes damages arising from any viruses or other harmful code that may infect your computer equipment. INSYS Therapeutics, Inc., may make changes to these materials at any time without notice, and makes no commitment to update the information contained herein.

This website may link you to other websites that are not owned or controlled by INSYS Therapeutics, Inc. These links are provided for your convenience only. These sites are maintained by entities over which INSYS Therapeutics, Inc., exercises no control. Accordingly, INSYS Therapeutics, Inc., expressly disclaims any responsibility for the content, the accuracy of the information, and/or quality of products or services provided by or advertised on these third-party sites. If you choose to hyperlink to another website, you do so at your own risk.