Subsys

Name: Subsys

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Side effects

The following serious adverse reactions are described, or described in greater detail, in other sections:

  • Life-Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS]
  • Interactions with Benzodiazepines and other CNS Depressants [see WARNINGS AND PRECAUTIONS]
  • Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
  • Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
  • Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
  • Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
  • Severe Hypotension [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of SUBSYS has been evaluated in a total of 359 opioid-tolerant patients with breakthrough cancer pain. The duration of SUBSYS use varied during the open-label study. Safety data from a longterm extension study showed that the average duration of therapy in the open-label study was 66 days. The maximum duration of therapy was 149 days. The dose range studied in these trials ranged from 100 mcg per dose to 1600 mcg per dose.

The most serious adverse reactions associated with all opioids including SUBSYS are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. Follow all patients for symptoms of respiratory depression.

The most common adverse reaction leading to discontinuation of SUBSYS was nausea. There were also adverse reactions of abdominal distension, anorexia, confusional state, disorientation, somnolence, and constipation.

The clinical trials of SUBSYS were designed to evaluate safety and efficacy in treating breakthrough cancer pain; all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent cancer pain. The adverse event data presented here reflect the actual percentage of patients experiencing each adverse effect among patients who received SUBSYS for breakthrough cancer pain along with a concomitant opioid for persistent cancer pain.

Table 4 lists adverse reactions with an overall frequency of 5% or greater that occurred during titration in the clinical trials. Adverse reactions are listed in descending order of frequency within each system organ class.

Table 4: Percent of Patients with Specific Adverse Events During Titration in the Clinical Trials (Events in 5% or More of Patients)

System Organ Class Titration
n=359 (%)
Gastrointestinal Disorders
  Nausea 47 (13.1%)
  Vomiting 37 (10.3%)
  Constipation 18 (5.0%)
Nervous System Disorders
  Somnolence 34 (9.5%)
  Dizziness 26 (7.2%)

The following adverse reactions occurred during titration in the clinical trials with an overall frequency of 1% or greater and are listed in descending order of frequency within each system organ class.

Cardiac Disorders: Tachycardia

Gastrointestinal Disorders: Diarrhea, stomatitis, dry mouth

General Disorders and Administration Site Conditions: Application site irritation, pyrexia, edema peripheral, fatigue, asthenia

Metabolism and Nutrition Disorders: Decreased appetite

Nervous System Disorders: Lethargy, sedation, tremor, headache

Psychiatric Disorders: Depression, confusional state, hallucination, insomnia

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea

Skin and Subcutaneous Tissue Disorders: Pruritus

The following reactions occurred during titration in the clinical trials with an overall frequency of less than 1% and are listed in descending order of frequency within each system organ class.

Eye Disorders: Vision blurred, dry eye

Gastrointestinal Disorders: Abdominal pain

Infections and Infestations: Oral candidiasis, cellulitis

Injury, Poisoning and Procedural Complications: Fall

Metabolism and Nutrition Disorders: Dehydration, anorexia

Musculoskeletal and Connective Tissue Disorders: Back pain, arthralgia, joint swelling

Psychiatric Disorders: Anxiety, agitation

Renal and Urinary Disorders: Urinary retention

Respiratory, Thoracic and Mediastinal Disorders: Cough, increased bronchial secretion, dysphonia, pharyngolaryngeal pain

Skin and Subcutaneous Tissue Disorders: Hyperhidrosis

Vascular Disorders: Hot flush

Table 5 lists adverse reactions with an overall frequency of 5% or greater for the total safety database subsequent to titration during the clinical trials.

Table 5: Adverse Reactions Subsequent to Titration in 5% or More of Patients

System Organ Class Dosing
n=269
Gastrointestinal Disorders
  Vomiting 43 (16.0%)
  Nausea 28 (10.4%)
  Constipation 28 (10.4%)
General Disorders and Administration Site Conditions
  Asthenia 26 (9.7%)
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea 28 (10.4%)
Psychiatric Disorders
  Anxiety 16 (5.9%)

The following adverse reactions occurred during the dosing period of the clinical trial with an overall frequency of 1% or greater and are listed in descending order of frequency within each system organ class.

Blood and Lymphatic System Disorders: Anemia, neutropenia, lymphadenopathy, thrombocytopenia, leukopenia

Cardiac Disorders: Tachycardia, sinus tachycardia

Gastrointestinal Disorders: Diarrhea, stomatitis, abdominal pain, abdominal distension, gastritis, dysphagia, dyspepsia, gastroesophageal reflux disease, ascites, hematemesis

General Disorders and Administration Site Conditions: Edema peripheral, fatigue, pyrexia, chest pain, drug withdrawal syndrome, chills, irritability, malaise, application site irritation

Infections and Infestations: Oral candidiasis, pneumonia, urinary tract infection, oral herpes, gastroenteritis, laryngitis

Injury, Poisoning and Procedural Complications: Contusion

Investigations: Weight decreased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood glucose increased, blood lactate increased

Metabolism and Nutrition Disorders: Anorexia, dehydration, hypokalemia, decreased appetite, hyponatremia, hypocalcemia, hypoalbuminemia, cachexia

Musculoskeletal and Connective Tissue Disorders: Back pain, arthralgia, muscular weakness

Nervous System Disorders: Hypoesthesia, lethargy, sedation, tremor, somnolence, headache, dizziness

Psychiatric Disorders: Depression, restlessness, agitation, confusional state, insomnia, hallucination, disorientation

Renal and Urinary Disorders: hypertension, hypotension

Respiratory, Thoracic and Mediastinal Disorders: Cough, increased bronchial secretion, wheezing, pharyngolaryngeal pain, hypoxia, dyspnea exertional

Skin and Subcutaneous Tissue Disorders: hyperhidrosis, pruritus

In a single-dose mucositis study, a group of patients with Grade 1 or 2 oral mucositis (n=9) and without oral mucositis (n=9) were included in a clinical trial designed to support the safety of SUBSYS. Two of the nine subjects with mucositis (one with Grade 1 and one with Grade 2) reported a burning sensation in the oral mucosa after treatment. Both of these events were considered mild and probably related to treatment. There was no change in grade of mucositis after treatment for any subject.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of fentanyl. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in SUBSYS.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Subsys Overview

Fentanyl is a prescription medication used to treat breakthrough cancer pain. It can also be used as part of surgical anesthesia.

Fentanyl belongs to a group of drugs called opioid agonists or narcotic pain medications. These work by changing the way the brain and nervous system respond to pain.

This medication comes in nasal spray, sublingual spray, sublingual (buccal) tablet, lozenge, and transdermal patch forms. The dose and frequency of administration will vary with the indication and dosage form.

This medication is also available in an injectable form to be given directly into a vein (IV) or the muscle (IM) by a healthcare professional.

Common side effects of fentanyl include difficulty breathing, nausea, upset stomach, and difficulty urinating.

Fentanyl can also cause changes in vision, drowsiness, and dizziness. Do not drive or operate heavy machinery until you know how fentanyl affects you.

Subsys Food Interactions

Grapefruit and grapefruit juice may interact with fentanyl and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Inform MD

Before taking fentanyl, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to fentanyl or to any of its ingredients
  • are taking herbal supplements, especially St. John’s Wort
  • drink large amounts of alcohol or use illegal drugs
  • have had a head injury, brain tumor, stroke, or seizures
  • have liver problems
  • have kidney problems
  • have heart problems, especially problems with your heart rate
  • have low blood pressure
  • have mental illness, such as depression, schizophrenia, or hallucinations
  • have breathing disorders, such as asthma or chronic obstructive pulmonary disorder
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

 

Other Requirements

  • Store fentanyl at room temperature.
  • Keep this and all medicines out of the reach of children.
  • Special instructions for discarding used and unused fentanyl doses are provided in the medication guide you will receive with your medication. Follow these instructions carefully and ask your pharmacist for more information or if you are unclear how to dispose of fentanyl products safely.

Uses of Subsys

  • It is used to ease pain.
  • This medicine is not for mild pain or pain that only lasts a short time (like headaches, toothaches, or pain after surgery).

What do I need to tell my doctor BEFORE I take Subsys?

  • If you have an allergy to this medicine (Subsys) or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine (Subsys) within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you are taking any of these drugs: Buprenorphine, butorphanol, nalbuphine, or pentazocine.
  • If have sores in your mouth, talk with your doctor.
  • If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with this medicine (Subsys).

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How do I store and/or throw out Subsys?

  • Store at room temperature. Do not freeze.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Follow the information that comes with this medicine (Subsys) for throwing out doses that are not needed. Check with your pharmacist if you have questions about how to throw out this medicine.

PRINCIPAL DISPLAY PANEL - NDC 20482-006-30 - 600 mcg 30-ct Carton Label



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