March 23, 2017
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Subsys

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Subsys

SUBSYS®
(fentanyl) Sublingual Spray

WARNING

LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; REMS and NEONATAL OPIOID WITHDRAWAL SYNDROME

Life-Threatening Respiratory Depression

Serious, life-threatening, and/or fatal respiratory depression has occurred in patients treated with SUBSYS, including following use in opioid non-tolerant patients and improper dosing. Monitor for respiratory depression, especially during initiation of SUBSYS or following a dose increase. The substitution of SUBSYS for any other fentanyl product may result in fatal overdose [see WARNINGS AND PRECAUTIONS]

Due to the risk of respiratory depression, SUBSYS is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients. [see CONTRAINDICATIONS]

Accidental Ingestion

Accidental ingestion of even one dose of SUBSYS especially by children, can result in a fatal overdose of fentanyl [see WARNINGS AND PRECAUTIONS].

Death has been reported in children who have accidentally ingested transmucosal immediaterelease fentanyl products. SUBSYS must be kept out of reach of children [see WARNINGS AND PRECAUTIONS; HOW SUPPLIED/Storage and Handling].

Cytochrome P450 3A4 Interaction

The concomitant use of SUBSYS with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse reactions 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 SUBSYS and any CYP3A4 inhibitor or inducer [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS].

  • Reserve concomitant prescribing of SUBSYS and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

Risk of Medication Errors

Substantial differences exist in the pharmacokinetic profile of SUBSYS compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].

  • When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to SUBSYS.
  • When dispensing, do not substitute a SUBSYS prescription for other fentanyl products.

Addiction, Abuse, and Misuse

SUBSYS exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing SUBSYS, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS AND PRECAUTIONS].

Risk Evaluation and Mitigation Strategy (REMS) Access Program

Because of the risk for misuse, abuse, addiction, and overdose, SUBSYS is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. [see WARNINGS AND PRECAUTIONS]. Further information is available at www.TIRFREMSaccess.com or by calling 1-866-822-1483.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of SUBSYS during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

SUBSYS (fentanyl sublingual spray) is an opioid agonist, available as a sublingual spray designed to deliver doses of 100, 200, 400, 600, 800, 1200 and 1800 mcg of fentanyl. The chemical name of fentanyl is N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]propanamide.

SUBSYS®(fentanyl) Structural Formula Illustration

Fentanyl is a highly lipophilic compound (octanol-water partition coefficient at pH 7.4 is 860:1) that is freely soluble in ethanol and methanol and practically insoluble in water (1:40). The molecular weight of the free base is 336.47. The pKa is 8.4.

The inactive ingredients in SUBSYS include: dehydrated alcohol 63.6% (V/V), purified water, propylene glycol, xylitol, and L-menthol.

Last reviewed on RxList: 1/6/2017
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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