July 28, 2016
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"Young children have died or become seriously ill from accidental exposure to a skin patch containing fentanyl, a powerful pain reliever. As a result of this, the Food and Drug Administration (FDA) is issuing a Drug Safety Communication to warn pa"...



Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

(fentanyl iontophoretic) Transdermal System



Life-Threatening Respiratory Depression

  • Use of IONSYS may result in potentially life-threatening respiratory depression and death as a result of the active drug, fentanyl. Only the patient should activate IONSYS dosing [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
  • Accidental exposure to an intact IONSYS or to the hydrogel component, especially by children, through contact with skin or contact with mucous membranes, can result in a fatal overdose of fentanyl [see WARNINGS AND PRECAUTIONS].
  • IONSYS is for use only in patients in the hospital. Discontinue treatment with IONSYS before patients leave the hospital [see WARNINGS AND PRECAUTIONS].

IONSYS Risk Evaluation and Mitigation Strategy (REMS) Program

  • Because of potentially life-threatening respiratory depression resulting from accidental exposure, IONSYS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the IONSYS REMS Program [see WARNINGS AND PRECAUTIONS].

Addiction, Abuse, and Misuse

  • IONSYS exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor regularly for development of these behaviors or conditions [see WARNINGS AND PRECAUTIONS].

Cytochrome P450 3A4 Interaction

  • The concomitant use of IONSYS with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving IONSYS and any CYP3A4 inhibitor or inducer [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].


Chemical Characteristics Of Drug Substance And Product

IONSYS (fentanyl iontophoretic transdermal system) is a patient-controlled iontophoretic transdermal system providing on-demand systemic delivery of fentanyl, an opioid agonist, for up to 24 hours or a maximum of 80 doses, whichever comes first.

The chemical name is propanamide, N-phenyl-N-[1-(2-phenylethyl)-4- piperidinyl] monohydrochloride. The structural formula is:

IONSYS® (fentanyl) Structural Formula Illustration

The molecular weight of fentanyl hydrochloride is 372.93, and the empirical formula is C22H28N2O•HCl. The n-octanol:water partition coefficient is 860:1; the pKa is 8.4.

The active ingredient in IONSYS is fentanyl. IONSYS contains 10.8 mg of fentanyl hydrochloride equivalent to 9.7 mg of fentanyl. IONSYS is designed to deliver a 40 mcg dose of fentanyl (equivalent to 44.4 mcg of fentanyl hydrochloride) over a 10-minute period upon each activation of the dose button [see DOSAGE AND ADMINISTRATION].

The inactive ingredients in the IONSYS hydrogels consist of cetylpyridinium chloride, USP; citric acid, USP; polacrilin; polyvinyl alcohol; sodium citrate, USP; sodium chloride, USP; sodium hydroxide; and purified water, USP.

System Components And Structure

Each IONSYS (see Figure 8) is composed of a plastic top housing that contains the battery and electronics and a red plastic bottom housing containing two hydrogel reservoirs and a polyisobutylene skin adhesive. Only one of the hydrogels (the anode, located under the dosing button) contains fentanyl HCl, along with inactive ingredients. The other hydrogel (the cathode) contains only pharmacologically inactive ingredients. The bottom housing has a red tab that is used for IONSYS removal from the skin and during disposal [see DOSAGE AND ADMINISTRATION]. A siliconized clear, plastic release liner covers the hydrogels and must be removed and discarded prior to placement on the skin. IONSYS is powered by a 3-volt lithium battery.

Figure 8 : IONSYS® (fentanyl iontophoretic transdermal system)

IONSYS® (fentanyl iontophoretic transdermal system) Illustration

*Light is off or on (blinks and displays red or green color light)

What are the possible side effects of fentanyl transdermal (Ionsys)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have any of these serious side effects:

  • weak, shallow breathing;
  • severe weakness, feeling light-headed or fainting;
  • cold, clammy skin; or
  • pale skin, easy bruising or bleeding.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, constipation, gas;
  • dizziness, drowsiness, anxiety, sleep problems...

Read All Potential Side Effects and See Pictures of Ionsys »

Last reviewed on RxList: 9/8/2015
This monograph has been modified to include the generic and brand name in many instances.

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

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