Fentanyl – Oral

What Is Fentanyl - Oral?

Fentanyl is an orally administered prescription medication used to treat breakthrough pain that occurs despite the use of regular opioid doses in people who require around-the-clock opioid treatment as a result of breakthrough cancer pain. Breakthrough pain is defined as severe pain that comes while a person is already medicated with a long-acting drug.

Fentanyl is a type of opioid, a class of highly addictive painkillers. Fentanyl works by attaching to opioid receptors, which are found in the central nervous system (CNS) and other parts of your body. By attaching to receptors in your brain, fentanyl blocks pain signals, which results in analgesia, meaning pain relief that doesn't put you to sleep.

Opioids like fentanyl attach to receptors in other parts of your body as well, which may cause additional effects such as sleepiness, nausea, constipation, bradycardia (slow heart rate), and trouble breathing.

Additionally, fentanyl, as with almost all narcotics, is a Schedule II drug, meaning it's a controlled substance. It is highly regulated by the United States (U.S.) Controlled Substances Act.

This law was passed to regulate the possession, use, and manufacturing of drugs that have a high potential for misuse, abuse, or addiction.

Oral fentanyl is available as a lozenge under the brand name, Actiq, and as a buccal tablet, under the brand name, Fentora.

Buccal tablets refer to a drug that is given between the gums and the inner lining of a person's cheek, specifically labeled the buccal pouch. In comparison, lozenges are intended to be dissolved slowly in the mouth. They often contain one or more active ingredients and are flavored to be pleasant tasting.

This article will discuss the uses, side effects, and dosages associated with oral fentanyl.

What Is Fentanyl Used For?

The FDA has approved oral fentanyl for the treatment of breakthrough pain in people who have cancer. It should only be used in people who are opioid-tolerant and who are already using opioids around-the-clock, meaning they are regularly taking scheduled doses, as opposed to only using opioids as needed.

Actiq is approved for people 16 and older. Fentora is prescribed for people 18 and older.

It's important to know that "opioid tolerant" refers to those who are taking, for one week or longer:

• Around-the-clock medicine consisting of at least 60 milligrams of oral morphine per day
• At least 25 micrograms of transdermal (a patch that delivers drugs through skin absorption) fentanyl per hour
• At least 30 micrograms of oral oxycodone per day
• at least 8 milligrams of oral Dilaudid (hydromorphone HCl) per day
• At least 25 micrograms of oral oxymorphone per day
• At least 60 mg of oral hydrocodone per day
• Or an equianalgesic (the dose at which two opioids, at a steady state, provide the same pain relief) dose of another opioid

If you are using fentanyl as an outpatient (meaning out of the hospital), you will have to be enrolled in a special program called the Transmucosal Immediate-Release Fentanyl (TIRF) REMS ACCESS Program.

This special program allows for another layer of safety to make sure that the only people using fentanyl are those who really need it. If fentanyl is being used while you are admitted to a hospital, this enrollment is not required.

How to Take Fentanyl

While containing the same primary ingredient, Actiq and Fentora differ slightly in their dosing strength and frequency.

Users should note the following dosing guidelines and instructions before starting treatment:

Actiq initial dosage: 200 micrograms

• An Actiq buccal tablet should be consumed over 15 minutes. People should be prescribed an initial supply of six, 200 micrograms of Actiq, therefore limiting the number of tablets in the home.
• People should use up all tablets before increasing to a higher dose to prevent confusion and possible overdose.

Repeat dosing:

• In cases where the breakthrough pain episode is not relieved 15 minutes after completion of the Actiq lozenge (30 minutes after the start of the lozenge), people may take one additional dose using the same strength for that episode.
• You should take a maximum of two doses of Actiq for any episode of breakthrough pain.
• You must wait at least four hours before treating another episode of breakthrough pain with ACTIQ.

Fentora initial dosage: 100 micrograms

• The initial dose is always 100 micrograms with the only exception being people already using Actiq.

Repeat dosing:

• When a breakthrough pain episode is not relieved after 30 minutes, patients may take one additional dose using the same strength for that episode. People should take a maximum of two doses for any episode of breakthrough pain.
• Users must wait at least four hours before treating another episode of breakthrough pain with Fentora.
• If you are already taking Actiq, you must follow the "Initial Dosing Recommendations for Patients on Actiq." Your healthcare provider will walk you through this step.
  

General advice on dosing:

• Your healthcare provider will likely start you on a low dose of fentanyl and gradually increase your dose until you find the dose that will relieve your breakthrough pain.
• Generally, do not use fentanyl more than four times a day. Call your healthcare provider if you experience more than four episodes of breakthrough pain per day. They may need to adjust the dose of your other pain medication(s) to control your symptoms better.
• Swallow the buccal tablet whole; do not split, chew, or crush. Also do not chew or bite the lozenge, only suck on this medication as directed.
• Talk with your healthcare provider before you stop using fentanyl. Stopping opioids may result in withdrawal symptoms such as anxiety, tachycardia (fast heartbeat), nausea or vomiting, diarrhea, or abdominal pain.
  

Storage

Both Actiq and Fentora should be stored similarly:

Keep this medication in the packaging it came in and out of reach of children or pets. Store it in a safe place so that no one else can use it.

Use the child-resistant locks and other supplies provided by the manufacturer to keep children away from the lozenges. Keep track of how much fentanyl is left so you will know if any is missing. Store fentanyl at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze fentanyl.

Accidental exposure, particularly in children, can result in severe respiratory depression (trouble breathing) or even death.

If you have children in the household, ask your healthcare provider about getting a child safety kit that includes a portable carrying case, a lock for the bag, and a package of cabinet and drawer child safety latches for securing the storage space at home.

Dispose of unused fentanyl by flushing it down the toilet.

Off-Label Uses

Other fentanyl products have numerous uses, with nonspecific labeled indications covering a wide variety of pain types, such as postoperative pain (pain after going through surgery), bone and joint pain in osteoarthritis, and pain resulting from a major injury-causing accident.

What Are the Side Effects of Fentanyl?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your pharmacist or a healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 800-FDA-1088.

Common Side Effects

Whether you are consuming either Actiq, Fentora, or both, the following side effects are the most common among people taking opioid drugs, including fentanyl:

• Sedation, or sleepiness
• Nausea or vomiting
• Constipation
• Dizziness
• Headache
• Abdominal pain
  

Severe Side Effects

Both Actiq and Fentora carry a black box warning, which is the strongest warning issued by the FDA. Relevant to both brands, the warning advises:

• Serious and/or fatal respiratory depression has occurred. Monitor closely, especially when first using it or following a dose increase.
• Due to the risk of fatal respiratory depression, fentanyl is not prescribed to people who are not opioid-tolerant.
• Accidental ingestion of fentanyl, especially by children, can result in death. Keep out of the reach of children. 
• Simultaneous use of CYP3A4 inhibitors (or stopping CYP3A4 inducers) can result in a fatal overdose of fentanyl. Additionally, the simultaneous use of opioids with benzodiazepines or another CNS depressant, including alcohol, may result in sedation, respiratory depression, coma, and death.
• Fentanyl exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. It is available only through the TIRF REMS Access program.
• Extensive use of fentanyl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. 

Call your healthcare provider right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include the following as a result of fentanyl use:

• Respiratory depression occurs because opioids can hinder your brain’s ability to know when it needs you to take another breath. This can result in a buildup of carbon dioxide in your body. Symptoms may include trouble breathing and shallow, slow breaths. The risk of this is greatest during the first 24 to 72 hours after you start using fentanyl or after the dose increases.
• Anaphylaxis is a type of allergic reaction that can potentially occur after your first dose or at any time during treatment. Signs and symptoms may include trouble breathing, rash, and swelling of your throat and tongue. Call 911 or go to the emergency room if you experience a serious allergic reaction.
• Addiction, abuse, and misuse can result even when fentanyl is taken as recommended. These issues can lead to overdose and death. In addition to analgesia (pain relief), fentanyl can cause euphoric feelings, such as happiness and relaxation. It is possible for people to end up misusing drugs if they crave these euphoric feelings. Use extra caution if you have a personal or family history of substance use disorder or substance misuse.
• Adrenal insufficiency, also called Addison’s disease, is a potentially life-threatening condition in which your adrenal glands don’t produce enough of certain hormones. Signs and symptoms can be nonspecific (general), like nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension (low blood pressure). Seek medical attention if you experience multiple symptoms, as you may need replacement treatment with corticosteroids until adrenal function recovers.
• Orthostatic hypotension can result from taking fentanyl. Orthostatic hypotension can cause a sudden drop in blood pressure that results in a feeling of light-headedness that can cause syncope (fainting). This often occurs when you go from sitting or lying down for a period of time and then standing up quickly.
• Serotonin syndrome is rare but possible in people taking opioids, especially when also taking an antidepressant such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs). Cases range from mild to fatal. Symptoms can include confusion, hallucinations, agitation, headache, shivering, sweating, fever, fast heart rate, nausea, and diarrhea.

Long-Term Side Effects

Whether long-term side effects will develop and how long they will take to develop with prolonged use of fentanyl or other opioids is not well known.

Some studies show that long-term fentanyl use may increase the risk of fractures, infections, heart problems, sleep issues, gastrointestinal (GI) problems, overdose, and death due to overdose or other causes.

In addition to its misuse and abuse potential, fentanyl and other opioids may cause tolerance and dependence.

This means that after you take the drug for a given amount of time, you become dependent on it and need to continue taking it to avoid withdrawal symptoms.

Exactly how long it takes for this dependence to form or whether it will form at all is different for each person.

Dosage: How Much Fentanyl Should I Take?

Modifications

Regardless of the brand or route of administration, users should be aware of the following before beginning a fentanyl prescription:

In pregnancy: Prolonged use of fentanyl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if it’s not recognized and treated.

If your baby is continuously exposed to opioid medications before they’re born, they may display withdrawal symptoms at birth, including high-pitched crying or irritability, tremors, difficulty sleeping, diarrhea, or vomiting.

Chronic use of opioids may also cause reduced fertility. It is not known whether these effects on fertility are reversible. Make sure to discuss with your healthcare provider if you are pregnant, become pregnant, or planning to become pregnant.

In nursing people: Fentanyl is present in human breast milk. One study reports that the infant receives approximately 0.024% of the human dose. However, there is not enough information to determine how fentanyl affects the breastfed infant.

If you use fentanyl while nursing, monitor your baby for increased sleepiness, problems breathing, or limpness. Let your baby’s healthcare provider know right away if you notice these signs.

In children: The safety of fentanyl has not been established in children under 18 years old. Consult with a healthcare provider to discuss other options to manage the treatment of breakthrough cancer pain in your child.

In adults 65 and older: Older adults may be at greater risk for certain side effects of opioids such as respiratory depression and excessive sedation. The drug is also removed mostly by the kidneys, and older adults are more likely to have reduced kidney function.

If opioid use is considered necessary for older adults, it should always be started at the lowest possible dose and slowly titrated upward, as necessary.

Missed Dose

There’s no need to worry about missing a dose of fentanyl since you only use it when needed.

Remember not to use more than two doses per breakthrough pain episode, separated by no less than 30 minutes.

Overdose: What Happens If I Take Too Much Fentanyl?

Overdose with fentanyl, and opioid medications in general, is a large and growing concern in the U.S. This is why your healthcare provider should start you on the lowest fentanyl dose possible, and titrate up slowly and only if necessary.

Overdose symptoms may include respiratory depression, excessive sleepiness to the point of being difficult to wake up, coma, poor muscle control, cold and clammy skin, small pupils, and, in severe cases, slow heart rate, low blood pressure, atypical snoring, and death.

There is an antidote for opioid overdose called Narcan (naloxone), which comes as a nasal spray that can be given by a family member or caregiver in emergency overdose situations.

If you take opioids around-the-clock, you most likely have already heard of this product and should have it on hand at all times. Ask your healthcare provider if you have questions about Narcan.

In case of these symptoms, you will likely need emergency medical treatment. Call 911 if the symptoms feel severe or life-threatening.

Precautions

What Are Reasons I Shouldn't Take Fentanyl?

You shouldn’t take fentanyl if you are not opioid-tolerant. Life-threatening respiratory depression and death could occur at any dose in people who are not opioid-tolerant.

You also shouldn’t take fentanyl if any of the following apply to you:

• If you have acute or postoperative pain including headache or migraine and dental pain, or if you are in the emergency department
• If you have acute or severe asthma and are in a setting in which you can’t be monitored or receive emergency medical attention
• If you have a known or suspected gastrointestinal obstruction, including paralytic ileus
• If you have a known hypersensitivity (for example, you’ve experienced anaphylaxis or another allergic reaction) to fentanyl or components of fentanyl
  

What Other Medications May Interact With Fentanyl?

Fentanyl can have significant adverse effects when taken with certain other medications, as well as alcohol.

The following combinations are known to be dangerous and should be used with great caution if you’re also taking fentanyl and other opioids, the following list is relevant to both Actiq and Fentora:

• Other CNS depressants, like benzodiazepines, including Valium (diazepam), Xanax (alprazolam), alcohol, or muscle relaxers such as Flexeril (cyclobenzaprine) or Zanaflex (tizanidine), when taken with fentanyl may cause extreme sedation, respiratory depression, coma, and death.
• Serotonergic drugs may increase the amount of serotonin in your system. These include SSRIs such as Zoloft (sertraline), Paxil (paroxetine), and Celexa (citalopram); SNRIs like Cymbalta (duloxetine) and Effexor XR (venlafaxine); monoamine oxidase inhibitors (MAOIs) such as Nardil (phenelzine); or TCAs such as amitriptyline and Pamelor (nortriptyline). Taking any of these along with fentanyl may increase your risk for serotonin syndrome more than taking fentanyl alone does.

Fentanyl is metabolized (or processed and removed) by certain proteins called cytochromes, which also metabolize other drugs. When these proteins are too busy metabolizing fentanyl, other drugs can build up in your system, or vice versa.

For this reason, some dose adjustments may need to be made, or some other drugs avoided altogether:

• CYP3A4 inhibitors such as macrolide antibiotics (e.g., erythromycin), antifungal drugs (e.g., ketoconazole), and human immunodeficiency virus (HIV) protease inhibitors such as Norvir (ritonavir) may cause fentanyl to remain in your system longer and increase the risk of opioid side effects.
• CYP3A4 inducers such as rifampin, Tegretol (carbamazepine), Dilantin (phenytoin), or Saint-John’s-wort may cause fentanyl to clear faster from your body, and not work as well.

Always make your healthcare provider aware of any other prescription and other over-the-counter (OTC) medicines you take, as well as any herbal supplements.

What Medications Are Similar to Fentanyl?

Fentanyl is similar to other opioid medications in that they work similarly to relieve pain.

However, fentanyl is one of the most potent opioid drugs, meaning that a much smaller dose of it can provide the same relief as a larger dose of other opioids:

• Morphine: Available in many formulations including oral and injectable drugs
• Hysingla ER (hydrocodone) or Anexsia (hydrocodone/acetaminophen): Available only as oral medication products
• Dilaudid (hydromorphone): Available as an injection, oral solution, and an oral tablet
• Oxycontin (oxycodone): Available only as an oral medication
• Conzip (tramadol): Available orally as a Schedule IV medication

This is not a list of drugs recommended to take with fentanyl. In fact, you should not take these drugs together. Ask your pharmacist or a healthcare practitioner if you have questions.

How Can I Stay Healthy While Taking fentanyl?

Nobody should have to suffer severe pain. Sometimes more typical prescription or OTC types of analgesics, or painkillers, are simply not strong enough to tame intense pain. Still, there is undoubtedly a stigma surrounding the use of opioids, and with good reason.

A fine balance exists between properly controlling pain and minimizing the hazards that inevitably come with the use of opioids.

Educate yourself as much as you can regarding how opioid medications work, how to use them safely, and what kinds of side effects they can cause in the short term and potentially in the long term.

The safest way to use opioid medications is to understand and respect the risks, make and follow a plan with your healthcare provider, and keep the medication in a completely secure location away from children, pets, and even other family members if necessary.