Fentanyl

DESCRIPTION / DEFINITIONS: Fentanyl is a prescription painkiller intended to be prescribed for breakthrough cancer pain for patients already taking ‘round-the-clock opioids. Breakthrough pain is sudden bouts of pain that are not controlled by the doses of the patients’ regularly scheduled opioids. It is about 100 times more powerful than morphine, and 50 times more potent than heroin.

ABUSE: Fentanyl is highly abused. According to the Drug Enforcement Agency (DEA), the National Forensic Laboratory Information System – which reports on evidence analyzed in crimes – reports of fentanyl involvement increased from nearly 5,400 in 2014 to over 14,600 in 2015. A similar increase was reported from 2013 to 2014.

ADDICTION / DEPENDENCE:  Fentanyl is highly addictive, as is covered in the label’s black box warning. See below.

SIDE EFFECTS:  Side effects include a wide range of conditions including abdominal pain, adrenal insufficiency, agitation and anxiety, confusion, decreased sexual desire and ability, infertility, depression, fast heartbeat, swelling of the hands, arms, legs, feet, ankles, or lower legs, and more. See more information below.

WITHDRAWAL SYMPTOMS: Withdrawal from Fentanyl can be severe. Symptoms include abdominal cramps, chills, diarrhea, increased blood pressure, increased heart rate, increased respiratory rate, insomnia, joint aches and pains, muscle aches and pain, and insomnia. See more complete information below.

TREATMENT: Getting off Fentanyl can be a struggle. Call us to talk to a Detox Advisor about how to make Fentanyl  detox safe and more comfortable..

 

DESCRIPTION / DEFINITIONS

Fentanyl is a prescription painkiller 50 to 100 times more potent than morphine, and 50 times more potent than heroin.

It was developed for treatment of chronic cancer pain, especially for breakthrough pain – which are bursts of extreme pain that are not controlled by the regular opioid medications the person may be taking. It is also used for other, short-term painful situations such as migraine, an injury, or after a medical or dental procedure.

Fentanyl is available in several different forms – a tablet that is swallowed, a ‘lozenge’ (placed in the cheek to dissolve), a lollipop, as a spray, injections, or a transdermal patch (placed on the skin, through which the drug is absorbed). It is sometimes combined with bupivicaine (a local anesthetic), and is sold under these names:

  • Abstral Fentanyl (sublingual tablets)
  • Fentanyl – Nova Plus (an extended release patch)
  • Fentanyl Buccal
  • Fentanyl Citrate
  • Bupivacaine HCL
  • Fentanyl System (which is a patch)
  • Fentanyl Transdermal System (also a patch)
  • Sublimaze
  • Transmucosal Fentanyl Citrate
  • Abstral
  • Actiq (a lozenge)
  • Duragesic (a patch)
  • Fentora (a tablet)
  • Ionsys (an iontophoretic patch – meaning it is introduced into the body through the skin by applying a local electric current)
  • Lazandra (a spray)
  • Subsys (also a spray) and for veterinary use only
  • Recuvyra.

The oral forms are more dangerous and more prone to abuse, so Fentanyl is usually injected or prescribed as patches.

The danger of dependence and addiction is extremely high, as is covered in the Black Box Warning on the label of the drug:

WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; RISKS FROM CYTOCHROME P450 3A4 INTERACTION; RISKS FROM 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 fentanyl buccal tablets, including following use in opioid non-tolerant patients and improper dosing. Monitor for respiratory depression, especially during initiation of fentanyl buccal tablets or following a dose increase. The substitution of fentanyl buccal tablets for any other fentanyl product may result in fatal overdose.

Due to the risk of respiratory depression, fentanyl buccal tablets are contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients.

Accidental Ingestion

Accidental ingestion of even one dose of fentanyl buccal tablets, especially by children, can result in a fatal overdose of fentanyl

.

Death has been reported in children who have accidentally ingested transmucosal immediate-release fentanyl products. Fentanyl buccal tablets must be kept out of reach of children.

The concomitant use of fentanyl buccal tablets 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 fentanyl buccal tablets and any CYP3A4 inhibitor or inducer.

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.

  • Reserve concomitant prescribing of fentanyl buccal tablets 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 fentanyl buccal tablets compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl and that could result in fatal overdose.

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

Addiction, Abuse, and Misuse
Fentanyl buccal tablets expose 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 fentanyl buccal tablets, and monitor all patients regularly for the development of these behaviors or conditions.

Risk Evaluation and Mitigation Strategy (REMS) Access Program
Because of the risk for misuse, abuse, addiction, and overdose, fentanyl buccal tablets are 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. Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.

Neonatal Opioid Withdrawal Syndrome
Prolonged use of fentanyl buccal tablets 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.

ABUSE

Fentanyl can cause intense euphoria, which makes it a common drug of abuse. It is particularly dangerous because of its potency.

ADDICTION / DEPENDENCE

As with other opioids, Fentanyl is very easy to become dependent on and addicted to. But because it is so much stronger than other opioids, it is also more dangerous.

 

HALF LIFE AND METABOLISM

The biological half-life of a substance is the time it takes for a drug to lose half of its pharmacologic activity. This is significant because it affects how soon withdrawal symptoms may appear.

The half life of Fentanyl ranges from 3 hours to 22, depending on the form of the drug. For injection, it’s 3.5 – 4 hours, IV infusion 7.3-9.7 hours, and for the Fentanyl patch the average is 17 hours (ranging from13 to 22).

Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4).

The CYP enzymes are the major enzymes involved in drug metabolism, and since many drugs may increase or decrease the activity of various CYP isozymes, this is a major source of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels, possibly causing an overdose.

OPIOID INDUCED HYPERALGESIA

There is increasing medical research showing that taking opioids like Fentanyl for longer than six months will create a condition called Opioid Induced Hyperalgesia. This is a condition where the opioids actually make the pain receptors more sensitive and, therefore, make the pain greater. A person with this condition is required to take more and more of the opioid to try to address the pain but finds that the pain actually increases.

 

SIDE EFFECTS

Side effects from Fentanyl can be severe and serious. They include:

  • abdominal pain
  • adrenal insufficiency (after greater than one month of use) – the adrenal glands do not produce enough hormones. This can result in chronic, or long lasting, fatigue
    muscle weakness, loss of appetite, weight loss, abdominal pain, nausea, vomiting, diarrhea, low blood pressure that drops further when a person stands up, causing dizziness or fainting, irritability and depression, craving salty foods, hypoglycemia (low blood sugar), headache, sweating, irregular or absent menstrual periods, in women, loss of interest in sex.
  • agitation
  • anxiety
  • back pain
  • changes in heartbeat
  • changes in vision
  • chest pain
  • confusion
  • constipation
  • decreased blood pressure – which can make you feel dizzy or lightheaded when you get up quickly from sitting or lying down
  • decreased sexual desire
  • decreased urge to breathe
  • depression
  • diarrhea
  • difficulty breathing or swallowing
  • difficulty falling asleep or staying asleep
  • difficulty urinating
  • dizziness
  • drowsiness
  • dry mouth
  • extreme drowsiness
  • fainting or feeling faint
  • fast heartbeat
  • fever
  • gas
  • hallucinations (seeing things or hearing voices that do not exist)
  • headache
  • heartburn
  • hives
  • inability to get or keep an erection
  • infertility – it is not known it this is reversible
  • irregular menstruation
  • Itching
  • loss of coordination
  • nausea
  • pain, sores, or irritation in the mouth in the area where you placed the medication
  • rash
  • seizures
  • serotonin sydrome (when taken in combination with serotonergic drugs) -serotonin syndrome is a group of side effects that include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea, associated with serotonergic drugs. Serotonergic drugs are used to treat migraine, depression and other mood disorders.
  • severe muscle stiffness or twitching
  • shivering
  • shortness of breath
  • sleepiness
  • slow, shallow breathing
  • stiff muscles
  • stomach pain
  • sudden reddening of the face, neck, or upper chest
  • sweating
  • swelling of the hands, arms, legs, feet, ankles, or lower legs
  • swelling of the face, tongue or throat
  • tiredness
  • trouble breathing
  • trouble walking
  • uncontrollable shaking of a part of the body
  • unusual dreams
  • unusual thinking
  • vomiting
  • weight loss

 

WITHDRAWAL SYMPTOMS

Fentanyl withdrawal symptoms are similar to those of other opioid withdrawals but because the drug is so much more potent than other opioids, they may be more intense, painful and uncomfortable.

  • abdominal cramps
  • agitation
  • anorexia
  • anxiety
  • backache
  • chills
  • depression
  • diarrhea
  • dilated pupils
  • goosebumps
  • hair standing on end
  • headache
  • increased blood pressure
  • increased  heart rate
  • increased respiratory rate
  • insomnia
  • irritability
  • joint aches and pains
  • muscle aches and pain
  • nausea
  • nervousness
  • perspiration
  • pupil  dilation
  • restlessness
  • runny nose
  • shivering
  • sleeplessness
  • stomach cramping
  • sweating
  • trembling
  • vomiting
  • watery eyes
  • weakness
  • yawning

TREATMENT

Fentanyl withdrawal can be difficult. Because of the pain and discomfort, it is advisable to detox in a medically-supervised facility where you can receive medications and other treatment to help you get through it safely and more comfortably. Many who try to detox on their own go back onto the drug to avoid any more of the withdrawal symptoms. Call us to talk to a Detox Advisor.