Probuphine (buprenorphine)

Probuphine is a brand-name prescription drug that’s used to treat opioid dependence in certain people ages 16 years and older. Opioid dependence is now called opioid use disorder (OUD) by healthcare professionals.

Probuphine contains the active drug buprenorphine. Probuphine is used in people who have successfully stayed on OUD treatment using a different form of buprenorphine for an extended length of time. People must have used buprenorphine that:

• is taken under the tongue (sublingual administration) or on the inside of the cheek (buccal administration), and
• doesn’t exceed a dosage of 8 mg of buprenorphine each day

Probuphine is used as part of a treatment plan for OUD that includes counseling or behavioral therapy.

Probuphine comes as subdermal implants (implants that are inserted under your skin). Your healthcare provider will insert four 1-inch implant rods on the inner side of your upper arm. Probuphine implants stay in your arm for up to 6 months and release the drug over this period of time.

Is Probuphine a controlled substance?

Yes, Probuphine is a controlled substance. It’s classified as a Schedule III prescription drug. This classification means that Probuphine has an accepted medical use, but it also may cause physical or psychological (mental) dependence in some people. (With dependence, you need the drug in order to feel normal.) This drug may also be misused.

The Drug Enforcement Administration (DEA) created special rules for how controlled substances, including Schedule III drugs, can be prescribed and dispensed. Your doctor or pharmacist can tell you more about these rules.

Healthcare providers can only prescribe Probuphine after they’ve received training and certification that’s approved by the U.S. federal government.

Effectiveness

Probuphine has been found effective in treating opioid dependence. In a clinical study, people who had been successfully treating their opioid dependence with an appropriate oral form (taken by mouth) of buprenorphine were included.

The people in this 6-month study either received the Probuphine implant or continued their usual buprenorphine oral dose. Throughout the study, 63% of people using Probuphine did not misuse opioids. Of those who continued their oral buprenorphine dose, 64% had the same result.

A new form of treatment

Probuphine, which was approved in 2016, is the first implant to be approved by the Food and Drug Administration (FDA) to treat opioid dependence. Other available forms of medication for treating opioid dependence include oral tablets and injectable solutions.

Probuphine is available only as a brand-name medication. It’s not currently available in generic form.

Probuphine contains the active drug buprenorphine.

Probuphine can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Probuphine. These lists do not include all possible side effects.

For more information on the possible side effects of Probuphine, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome.

More common side effects

The more common side effects of Probuphine can include:

• reactions at the site of your implant, which may cause pain, redness, and itchiness
• nausea
• vomiting
• constipation
• headache
• toothache
• pain in your mouth and throat
• back pain
• depression

Most of these side effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk with your doctor or pharmacist.

Serious side effects

Serious side effects from Probuphine aren’t common, but they can occur. Call your doctor 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:

• Respiratory depression (slow and weak breathing). Symptoms can include:
  • shortness of breath
  • feeling sleepy
  • bluish-color to your lips, toes, and fingers
  • confusion
  • seizures
  • coma
  • in serious cases, death
• Central nervous system depression (slowed brain function). Symptoms can include:
  • blurred vision
  • confusion
  • slow or slurred speech
  • slow reflexes
  • excessive sleepiness
  • lack of energy
  • coma
• Adrenal gland problems. Symptoms can include:
  • weakness
  • nausea
  • vomiting
  • lack of energy
  • dizziness
  • low blood pressure
• Liver damage, including hepatitis (inflammation in your liver). Symptoms can include:
  • belly pain
  • loss of appetite
  • weight loss
  • dark-colored urine
  • yellowing of your skin and the whites of your eyes
  • itchy skin
  • nausea
• Increased blood pressure in your brain. Symptoms can include:
  • headache
  • confusion
  • pinpoint pupils (abnormally small pupils, which are the parts of your eyes that let light inside)
• Orthostatic hypotension (low blood pressure when you stand up quickly). Symptoms can include:
  • feeling dizzy or falling when you stand up or sit up too quickly
• Increased blood pressure in your biliary tract (an area of your body that includes your liver, gallbladder, and bile ducts). Symptoms can include:
  • itchy skin
  • belly pain
  • loss of appetite
  • nausea
  • dark-colored urine

Other serious side effects, which are discussed below in the “Side effect details” section, include the following:

• severe allergic reactions
• severe complications from implant placement or removal, including implant movement, infection, nerve damage, and blood clots*

* Probuphine has a boxed warning from the FDA regarding the risk of complications with implant placement and removal. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Side effect details

You may wonder how often certain side effects occur with this drug. Here’s some detail on several of the side effects this drug may cause.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Probuphine. It’s not known how often people using Probuphine have allergic reactions to the drug. Symptoms of a mild allergic reaction can include:

• skin rash
• itchiness
• hives (swollen and raised red bumps on your skin)

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

• swelling under your skin, typically in your eyelids, lips, hands, or feet
• swelling of your tongue, mouth, or throat
• bronchospasm (tightening of the muscles in your airways)
• trouble breathing

Call your doctor right away if you have a severe allergic reaction to Probuphine. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Headache

You may have headaches while you’re using Probuphine. This is one of the more common side effects of the drug.

In clinical studies, 14% of people using Probuphine had headaches. Of people who took either sublingual buprenorphine (a tablet placed under their tongue) or a placebo (treatment with no active drug), 11% had headaches.

If you have headaches during Probuphine treatment, talk with your doctor about safe ways to ease your discomfort.

Complications from implant insertion and removal

Complications from inserting and removing Probuphine implants are rare, but they can be life-threatening. In fact, the risk of complications is so serious that the Food and Drug Administration (FDA) has required Probuphine to have a boxed warning about this side effect.

A boxed warning is the most serious warning from the FDA. It informs healthcare providers and patients about certain risks of the drug.

Complications of Probuphine implant insertion (placing the implant under your skin) and removal include:

• migration (movement) of the implant into areas of your body near the implant site or outside of your skin
• migration of the implant to your lungs, which can cause blood clots and even death
• infections in your skin or the area near the implant site

A long-term side effect of these complications can be permanent nerve damage in your arm. Nerve damage can cause tingling, numbness, or decreased sensation (ability to feel) in your arm.

In clinical studies, 37% of people who received a Probuphine implant had complications from the insertion or removal. Of those who received a placebo (no active treatment) implant, 27% had complications from insertion or removal.

Preventing or managing complications

Because the risks of Probuphine implant insertion and removal are so serious, only specially certified healthcare providers are qualified to insert or remove the implant.

After your implant has been inserted, you’ll return to your doctor’s office in about a week. At that time, your doctor will check to make sure there aren’t any problems with your implant, such as movement of the device. Your doctor will also check for signs of infection or problems with healing around the area of the implant.

If you’re concerned about the placement of your implant, let your doctor know. Call your doctor right away if you’re able to see the implant outside of your skin, or if the implant comes out of your arm.

You should also call your doctor if you feel numbness or tingling in the arm the implant is placed in. If the implant sticks out of your arm or comes completely out, don’t allow others to touch the implant. Put the implant in a plastic bag and bring it to your doctor’s office.

Side effects in children

Probuphine is not approved for use in children younger than 16 years of age. Side effects seen in children ages 16 through 17 years are expected to be similar to those seen in adults.

It’s important that children avoid contact with Probuphine implants. Touching or ingesting the implant can cause severe, life-threatening respiratory depression (slow and weak breathing) in children. If your implant sticks out of or falls out of your skin, be sure that any children present aren’t able to touch or make contact with the implant.

Probuphine can interact with several other medications.

Different interactions can cause different effects. For instance, some interactions can interfere with how well a drug works. Other interactions can increase side effects or make them more severe.

Probuphine and other medications

Below are lists of medications that can interact with Probuphine. These lists do not contain all the drugs that may interact with Probuphine.

Before taking Probuphine, talk with your doctor and pharmacist. Tell them about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Probuphine and naltrexone

Taking Probuphine with naltrexone (Vivitrol) can cause opioid withdrawal symptoms in people who are dependent on opioids. (With dependence, your body needs the drug in order for you to feel normal.) This is because naltrexone blocks the effects of buprenorphine (the active drug in Probuphine) in your body.

You shouldn’t take Probuphine with naltrexone unless your doctor advises you to do so.

Probuphine and tramadol or other opioids

Taking Probuphine with tramadol or other opioids (strong pain relievers) increases your risk for serious side effects. These side effects include:

• respiratory depression (slow and weak breathing)
• coma
• severe sleepiness
• in serious cases, death

Because of these risks, you shouldn’t take Probuphine with tramadol or any other opioid pain relievers. Examples of pain relievers that can increase your risk of serious side effects if taken with Probuphine include:

• tramadol (ConZip, Ultram)
• hydrocodone (Zohydro ER, Hysingla ER)
• oxycodone (Roxicodone, Xtampza ER, Oxycontin)
• hydromorphone (Dilaudid)
• morphine (Kadian, MS Contin)
• fentanyl (Abstral, Actiq, Duragesic, Subsys)

Many combination medications, which are made from more than one active drug, may also contain opioids. An example is Tylenol with codeine (codeine is an opioid). Be sure to tell your doctor about all pain medications that you’re taking.

Probuphine and certain anxiety drugs

Taking Probuphine with certain anxiety drugs called benzodiazepines increases your risk for serious side effects. These side effects include:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

Because of these risks, you shouldn’t take Probuphine with benzodiazepines unless you don’t have any other treatment option for your anxiety. Examples of benzodiazepines that can increase your risk of serious side effects if taken with Probuphine include:

• alprazolam (Xanax, Xanax XR)
• clonazepam (Klonopin)
• chlordiazepoxide (Librium)
• diazepam (Valium)
• lorazepam (Ativan)

If you need to take one of these drugs with Probuphine, your doctor will likely prescribe the lowest dose of the anxiety drug that’s effective to treat your anxiety. Your doctor will also monitor you closely for serious side effects.

Probuphine and certain muscle relaxants

Taking Probuphine with certain muscle relaxants can increase your risk for serious side effects. These include:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

You shouldn’t take certain muscle relaxants with Probuphine unless there aren’t any other treatment options for your muscle condition. Examples of muscle relaxants that can increase your risk of serious side effects if taken with Probuphine include:

• cyclobenzaprine (Amrix)
• carisoprodol (Soma)
• metaxalone (Skelaxin)
• tizanidine (Zanaflex)
• methocarbamol (Robaxin)

If you need to take one of these muscle relaxants with Probuphine, your doctor will likely prescribe the lowest dose of the muscle relaxant that’s effective for you. They’ll also monitor you closely for serious side effects.

Probuphine and certain antibiotics and antifungals

Taking Probuphine with certain antibiotics or antifungals could increase your risk of serious side effects from Probuphine. This is because some antibiotics and antifungals block your body from breaking down Probuphine. This leads to higher Probuphine levels in the body.

Increased levels of Probuphine can lead to serious side effects, such as:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

Examples of antibiotics that can increase your risk of side effects if taken with Probuphine include:

• clarithromycin (Biaxin XL)
• erythromycin (Ery-Tab, Eryped, many others)

Examples of antifungals that can increase your risk of side effects if taken with Probuphine include:

• ketoconazole (Extina, Nizoral, Xolegel)
• fluconazole (Diflucan)
• itraconazole (Omnel, Sporanox, Tolsura)
• voriconazole (Vfend)

If you need to take one of these antibiotics or antifungals while you’re using Probuphine, your doctor will monitor you closely for side effects from Probuphine.

Probuphine and certain antidepressants

Taking Probuphine with certain antidepressants can increase your risk of serotonin syndrome. With this serious condition, high levels of serotonin (a brain chemical) build up in your body. Symptoms of serotonin syndrome can include:

• fever
• anxiety
• confusion
• muscle spasms
• diarrhea
• seizures

Examples of antidepressants that can increase your risk of serotonin syndrome if taken with Probuphine include:

• citalopram (Celexa)
• escitalopram (Lexapro)
• paroxetine (Paxil, Brisdelle, Pexeva)
• duloxetine (Cymbalta)
• venlafaxine (Effexor XR)
• amitriptyline
• selegiline (Emsam, Zelapar)
• phenelzine (Nardil)

There are many other antidepressants that can cause serotonin syndrome if taken with Probuphine. If you need treatment with an antidepressant, talk with your doctor about a safe option for you.

If you’re taking one of these antidepressants with Probuphine, your doctor will monitor you closely for symptoms of serotonin syndrome. If you develop serotonin syndrome because of this drug interaction, they’ll likely recommend that you stop taking either Probuphine or the antidepressant medication.

Probuphine and certain insomnia drugs

Taking Probuphine with certain drugs that are used to treat insomnia (trouble sleeping) can increase your risk for serious side effects. These side effects include:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

Examples of insomnia medications that can increase your risk for serious side effects if taken with Probuphine include:

• trazodone
• zolpidem (Ambien, Edluar, Zolpimist)
• eszopiclone (Lunesta)
• ramelteon (Rozerem)
• zaleplon (Sonata)

If you need to take an insomnia medication while you’re using Probuphine, your doctor will likely prescribe the lowest dose of the insomnia medication that’s effective for you. They’ll also monitor you more closely for side effects of Probuphine.

Probuphine and certain diuretics

Taking Probuphine with certain diuretics (also called water pills) can decrease the effectiveness of the diuretics. This can lead to increased blood pressure or swelling.

Examples of diuretics that may not be as effective if taken with Probuphine include:

• furosemide (Lasix)
• torsemide (Demadex)
• bumetanide (Bumex)
• hydrochlorothiazide
• triamterene (Dyrenium)
• spironolactone (Aldactone, CaroSpir)

Many diuretics also come in combination medications that are used to treat heart disease or high blood pressure. Some combination medications, which are made from more than one drug, contain a diuretic. Be sure to tell your doctor about all the medications you’re taking.

If you need to take a diuretic with Probuphine, your doctor will monitor you closely for increased blood pressure and swelling. If needed, your doctor may increase the dosage of your diuretic.

Probuphine and certain seizure drugs

Taking Probuphine with certain seizure medications can increase how quickly your body breaks down and clears Probuphine. This could decrease the effectiveness of Probuphine for you.

Examples of seizure drugs that can decrease the effectiveness of Probuphine include:

• carbamazepine (Carbatrol, Epitol, Equetro, Tegretol)
• phenytoin (Dilantin, Phenytek)
• phenobarbital

If you need to take Probuphine with one of these seizure drugs, your doctor will monitor you closely for decreased effectiveness of Probuphine. They may recommend a different medication to treat either your opioid dependence or your seizures.

Probuphine and certain HIV drugs

Taking Probuphine with certain antiviral drugs that are used to treat HIV can affect Probuphine levels in your body.

Antivirals that decrease the effectiveness of Probuphine

Some antiviral drugs increase how quickly Probuphine is cleared from your body. This can decrease how effective Probuphine is for you. Examples of these antivirals include:

• efavirenz (Sustiva)
• etravirine (Intelence)
• nevirapine (Viramune)

If you need to take one of these drugs with Probuphine, your doctor will monitor you closely for decreased effectiveness of Probuphine. If needed, they may recommend a different treatment for your opioid dependence.

Antivirals that increase the side effects of Probuphine

Some antiviral drugs can prevent the breakdown of Probuphine. This causes increased Probuphine levels in your body, which can lead to serious side effects. These side effects include:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

Examples of antiviral drugs that can cause increased side effects if taken with Probuphine include:

• delavirdine (Rescriptor)
• atazanavir (Reyataz)
• ritonavir (Norvir)

If you need to take one of these antivirals with Probuphine, your doctor will monitor you closely for serious side effects. If you have serious side effects from Probuphine, your doctor may remove your Probuphine implant and prescribe a different medication for your opioid dependence.

Probuphine and gabapentin

Taking Probuphine with gabapentin (Neurontin, Gralise) may increase your risk for serious side effects. These side effects include:

• respiratory depression (slow and weak breathing)
• severe sleepiness
• coma
• in serious cases, death

You should only take gabapentin with Probuphine if your doctor advises you to do so.

Probuphine and herbs and supplements

There aren’t any herbs or supplements that have been specifically reported to interact with Probuphine. However, you should still check with your doctor or pharmacist before using any of these products while you’re taking Probuphine.

You shouldn’t drink alcohol while you’re taking Probuphine. This is because using them together increases your risk for serious side effects. These side effects, which can be life-threatening, include:

• slow, weak breathing
• sedation (sleepiness, trouble thinking clearly, and loss of coordination)
• coma
• death

If you’re considering treatment with Probuphine and you have trouble avoiding alcohol, talk with your doctor about whether Probuphine is right for you.

The following information describes the Probuphine dosage that is commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to suit your needs.

Drug forms and strengths

Probuphine comes as implants that are inserted under the skin of your upper arm, on the side that’s closest to your body. Probuphine can be placed into your left or right arm.

Probuphine implants are rod-shaped and 1 inch in length. They come in one strength: 80 mg of buprenorphine per implant.

When you have Probuphine placed, four implant rods will be inserted into your arm. The four implant rods hold a total of 320 mg of buprenorphine.

Dosage for opioid dependence

The usual dosage of Probuphine is four implant rods, which are all placed at the same time, under the skin of the inner side of your upper arm. Probuphine implants can stay in place for up to 6 months.

Each individual rod contains 80 mg of buprenorphine. With four implant rods placed, your total dose is 320 mg of buprenorphine.

Pediatric dosage

Probuphine is approved by the Food and Drug Administration (FDA) for use in children ages 16 years and older.

The usual recommended dosage for children is the same as it is for adults.

What if I miss a dose?

If you miss an appointment for Probuphine implant insertion or removal, call your doctor’s office right away. They’ll reschedule your appointment so that you can stay current on your dosing schedule.

To help make sure that you don’t miss an appointment, try setting a reminder on your phone.

Will I need to use this drug long term?

Probuphine is meant to be used as a long-term treatment. The Probuphine implant can remain in your arm for up to 6 months. It should be removed no later than 6 months after it was inserted.

If you and your doctor decide that continuing Probuphine therapy for another 6 months would be safe and effective for you, your doctor may prescribe a second implant. This would be placed in your other arm after your first implant is removed. It would be considered your second dose of Probuphine.

It’s not known if having a third dose of Probuphine or if having an implant inserted into an area that’s been used in the past would be safe.

Other drugs are available that can treat opioid dependence. Some may be better suited for you than others. If you’re interested in finding an alternative to Probuphine, talk with your doctor. They can tell you about other medications that may work well for you.

Alternatives for opioid dependence

Examples of other drugs that may be used to treat opioid dependence include:

• methadone (Dolophine, Methadose)
• naltrexone (Vivitrol)
• buprenorphine, other than Probuphine (such as Sublocade)
• buprenorphine/naloxone (Bunavail, Suboxone, Zubsolv)

You may wonder how Probuphine compares to other medications that are prescribed for similar uses. Here we look at how Probuphine and methadone are alike and different.

Uses

Probuphine is used to treat opioid dependence (also called opioid use disorder) in people ages 16 years and older. It’s used in people who’ve remained stable on another treatment that contains buprenorphine for at least 3 months. Their dosage of buprenorphine in this other treatment shouldn’t have been more than 8 mg per day.

Methadone is used for maintenance (ongoing) treatment of opioid dependence in adults. Methadone is also approved to manage severe pain and to help with detox from opioid dependence. Methadone comes in different forms, which have different approved uses.

Probuphine and methadone are each used in combination with counseling or behavioral therapy when they’re used to treat opioid dependence.

Drug forms and administration

Probuphine comes as implants that are inserted under the skin of the inner side of your upper arm.

Each Probuphine dose (made up of four 80-mg implant rods) contains a total of 320 mg of buprenorphine. The implant rods remain in your arm for up to 6 months at a time.

Methadone comes as:

• tablets that are taken by mouth (Dolophine, Methadose, and generic forms)
• tablets that are dissolved in liquid, which is then taken by mouth (Methadose and generic forms)
• solution that is taken by mouth (Methadose and generic forms)
• solution that is given by injection

Tablets are the most common form of methadone that’s used to treat opioid dependence. Methadone tablets, which are usually taken daily, come in three strengths: 5 mg, 10 mg, and 40 mg.

Side effects and risks

Probuphine and methadone are both opioids. Therefore, both medications can cause very similar side effects. Below are examples of these side effects.

More common side effects

These lists contain examples of more common side effects that can occur with Probuphine, with methadone, or with both drugs (when taken individually).

• Can occur with Probuphine:
  • reactions at the site of your implant, which may cause pain, redness, and itchiness
  • constipation
  • headache
  • toothache
  • pain in your mouth and throat
  • back pain
  • depression
• Can occur with methadone:
  • lightheadedness
  • dizziness
  • sweating
  • sedation (sleepiness, trouble thinking clearly, and loss of coordination)
• Can occur with both Probuphine and methadone:
  • nausea
  • vomiting

Serious side effects

These lists contain examples of serious side effects that can occur with Probuphine, with methadone, or with both drugs (when taken individually).

• Can occur with Probuphine:
  • severe complications from implant placement or removal, including implant movement, infection, nerve damage, or blood clots*
  • liver damage, including hepatitis (inflammation in your liver)
• Can occur with methadone:
  • long QT syndrome (a type of abnormal heart rhythm)*
• Can occur with both Probuphine and methadone:
  • respiratory depression (slow and weak breathing)*
  • central nervous system depression (slowed brain function)
  • adrenal gland problems
  • orthostatic hypotension (low blood pressure when you stand up quickly)
  • increased blood pressure in your brain
  • increased blood pressure in your biliary tract (an area of your body that includes your liver, gallbladder, and bile ducts)
  • severe allergic reaction

* Probuphine has a boxed warning from the FDA regarding the risk of complications with implant placement and removal. Methadone has a boxed warning regarding the risk of long QT syndrome and respiratory depression. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Effectiveness

Probuphine and methadone have different approved uses, but they’re both used to treat opioid dependence.

These drugs haven’t been directly compared in clinical studies. But separate studies have found both Probuphine and methadone to be effective for treating opioid dependence.

Costs

Probuphine is a brand-name drug. There are currently no generic forms of the Probuphine implant available. Methadone is available in brand-name forms (Methadose and Dolophine) and in generic forms. Brand-name medications usually cost more than generics.

Both the brand-name and generic forms of methadone generally cost less than Probuphine. The actual price you’ll pay for any drug depends on your insurance plan, your location, and the pharmacy you use.

Like methadone (described above), the drug naltrexone has uses similar to those of Probuphine. Here’s a comparison of how Probuphine and naltrexone are alike and different.

Uses

Probuphine is used to treat opioid dependence (also called opioid use disorder) in people ages 16 years and older. It’s used in people who’ve remained stable on another treatment that contained buprenorphine for at least 3 months. The dosage of buprenorphine in this other treatment shouldn’t have been more than 8 mg per day.

Naltrexone is used to prevent relapse (starting to use a drug after attempting to quit using it). It’s used in people who were dependent on opioids but have successfully stopped using opioids. These people shouldn’t have any opioids in their body for at least 7 to 10 days before starting naltrexone.

Naltrexone is also used to treat alcohol dependence. It’s used in people who are able to abstain from (avoid) alcohol, without needing to stay in a medical facility, before they start treatment with Naltrexone.

Probuphine and naltrexone should each be used as part of a complete treatment plan, which includes counseling or behavioral therapy.

Drug forms and administration

Probuphine comes as implants that are inserted under the skin of the inner side of your upper arm.

Each Probuphine dose (made up of four 80-mg implant rods) contains a total of 320 mg of buprenorphine. The implant rods remain in your arm for up to 6 months at a time.

Naltrexone comes in these two forms:

• a tablet that’s taken by mouth, which is available in generic forms
• a solution that’s given by injection into your muscle (an intramuscular injection), which is available in a brand-name form (Vivitrol)

The naltrexone tablets are typically taken once a day. They come in three strengths: 25 mg, 50 mg, and 100 mg.

The Vivitrol injection is given once every 4 weeks by a healthcare provider at a medical facility. Each injection contains 380 mg of naltrexone.

Side effects and risks

Probuphine and buprenorphine contain different drugs. Therefore, each medication can cause some similar and some different side effects. Below are examples of these side effects.

More common side effects

These lists contain examples of more common side effects that can occur with Probuphine, with buprenorphine, or with both drugs (when taken individually).

The side effects that you have from Naltrexone may also differ based on the form of naltrexone you’re taking.

• Can occur with Probuphine:
  • reactions at the site of your implant, which may cause pain, redness, and itchiness
  • constipation
  • headache
  • pain in your mouth and throat
  • back pain
  • depression
• Can occur with naltrexone:
  • pain at your injection site (when using Vivitrol)
  • common cold
  • insomnia (trouble sleeping)
  • anxiety
  • nervousness
  • belly pain
  • stomach cramps
  • low energy level
  • joint pain
  • muscle pain
• Can occur with both Probuphine and naltrexone:
  • toothache
  • nausea
  • vomiting
  • headache

Serious side effects

These lists contain examples of serious side effects that can occur with Probuphine, with naltrexone, or with both drugs (when taken individually).

• Can occur with Probuphine:
  • severe complications from implant placement or removal, including implant movement, infection, nerve damage, or blood clots*
  • respiratory depression (slow and weak breathing)
  • central nervous system depression (slowed brain function)
  • adrenal gland problems
  • increased blood pressure in your brain
  • orthostatic hypotension (low blood pressure when you stand up quickly)
  • increased blood pressure in your biliary tract (an area of your body that includes your liver, gallbladder, and bile ducts)
• Can occur with naltrexone:
  • severe injection site reactions (when using Vivitrol)
  • depression and having suicidal thoughts or behaviors
  • pneumonia
• Can occur with both Probuphine and naltrexone:
  • liver damage, including hepatitis (inflammation in your liver)
  • severe allergic reaction

* Probuphine has a boxed warning from the FDA regarding the risk of complications with implant placement and removal. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Effectiveness

Probuphine and naltrexone have different approved uses, but they’re both used to treat opioid dependence (also called opioid use disorder).

These drugs haven’t been directly compared in clinical studies. But separate studies have found both Probuphine and naltrexone (tablets and injection) to be effective for treating opioid dependence.

Costs

Probuphine and Vivitrol (the injectable form of naltrexone) are both brand-name drugs. There are currently no generic forms of the Probuphine implant or the Vivitrol injection. However, naltrexone tablets are available in generic forms. Brand-name medications usually cost more than generics.

Probuphine and Vivitrol generally cost about the same. Generic naltrexone tablets will be less expensive than either Probuphine or Vivitrol. The actual price you’ll pay for either drug depends on your insurance plan, your location, and the pharmacy you use.

The Food and Drug Administration (FDA) approves prescription drugs such as Probuphine to treat certain conditions. Probuphine may also be used off-label for other conditions. Off-label use is when a drug that’s approved to treat one condition is used to treat a different condition.

Probuphine for opioid dependence

Probuphine is FDA-approved to treat opioid dependence in people ages 16 years and older. Opioid dependence is now called opioid use disorder by healthcare professionals.

Probuphine is meant to be used as part of a complete treatment regimen that includes counseling or behavioral therapy.

What is opioid dependence?

Opioid dependence is also called opioid use disorder. This is a chronic (ongoing) disorder that can be caused by using opioids on a regular basis.

When someone is physically dependent on opioids, their body needs to continue receiving opioids in order for them to feel normal. When someone who is dependent on opioids stops taking opioids, they can have opioid withdrawal symptoms, such as anxiety, sweating, and diarrhea.

Who can take Probuphine?

Probuphine is used to treat opioid dependence in people who’ve been stable on another treatment that contains buprenorphine. Being stable on treatment means that:

• using the same dose of buprenorphine for at least 3 months has been effective to treat their opioid dependence
• no additional buprenorphine (above their treatment dose) was needed

The stable dose of buprenorphine that was used should’ve been taken by mouth, either under your tongue (sublingual administration) or on the inside of your cheek (buccal administration). The stable dose shouldn’t have been more than 8 mg of buprenorphine per day.

Examples of medications that contain buprenorphine and that are taken by mouth include:

• buprenorphine (generic forms)
• buprenorphine/naloxone (Suboxone, Bunavail, Zubsolv, generic forms)

Probuphine shouldn’t be used by people who:

• haven’t used buprenorphine therapy in the past
• aren’t able to abstain from (avoid) illicit drug use
• aren’t willing to participate in counseling or behavioral therapy
• within the past 90 days have either been hospitalized or had crises caused by drug misuse or mental health problems, such as hallucinations

Effectiveness for opioid dependence

Probuphine has been found effective in treating opioid dependence. A clinical study looked at people who had been successfully treating their opioid dependence with an oral form of buprenorphine. These included sublingual forms (which dissolve when placed under your tongue) and buccal forms (which dissolve when placed inside your cheek).

The people in this 6-month study either received the Probuphine implant or continued their usual buprenorphine oral dose. Throughout the study, 63% of people using Probuphine did not misused opioids. Of those who continued their oral buprenorphine dose, 64% had the same result.

Probuphine for other conditions

In addition to the use listed above, Probuphine may be used off-label. Off-label drug use is when a drug that’s approved for one use is used for a different one that’s not approved.

Probuphine for depression (off-label use)

Probuphine isn’t approved to treat depression, but it may sometimes be used off-label for this condition.

A review of several clinical studies found that buprenorphine (the active drug in Probuphine) may be effective, when given in low doses, in people who failed many other types of depression treatment. However, more studies are needed to determine buprenorphine’s role in treating depression.

If you have questions about treatment options for depression, talk with your doctor.

Probuphine for anxiety (off-label use)

Probuphine isn’t approved to treat anxiety, but sometimes it’s been used off-label for this condition.

A small clinical study found that people who took buprenorphine (the active drug in Probuphine) had fewer symptoms of anxiety after 1 week of treatment. However, it’s important to note that there wasn’t a comparison group (people with anxiety who weren’t taking buprenorphine) in this study.

If you have questions about treatment options for anxiety, talk with your doctor.

Probuphine and children

Probuphine is approved for use in children ages 16 years and older. It’s not approved for use in children younger than 16 years of age since it’s not known whether Probuphine is safe or effective for children of these ages.

Probuphine is meant to be used as part of a complete treatment plan for opioid dependence. This drug should be used in combination with counseling or therapy. Using these treatments together can help you be successful in staying on track with your treatment plan.

Forms of counseling or behavioral therapy that may be used with Probuphine include:

• inpatient hospital treatment programs
• individual or group therapy
• family therapy
• group homes

Talk with your doctor for more information about counseling or behavioral therapy programs that can help you reach your treatment goals.

Because Probuphine is given by a healthcare professional, it’s not likely that you’ll overdose on this drug. However, receiving more than the recommended dosage of Probuphine can lead to serious side effects.

Overdose symptoms

Symptoms of an overdose can include:

• sleepiness
• loss of coordination
• trouble thinking clearly
• pinpoint pupils (abnormally small pupils, which are the parts of your eyes that let light inside)
• sudden hypotension (drop in your blood pressure)
• respiratory depression (slow and weak breathing)
• death

What to do in case of overdose

If you think you’ve taken too much of this drug, call your doctor. You can also call the American Association of Poison Control Centers at 800-222-1222 or use their online tool. But if your symptoms are severe, call 911 or go to the nearest emergency room right away.

Naloxone: A lifesaver

Naloxone (Narcan, Evzio) is a drug that can quickly reverse overdoses from opioids, including heroin. An opioid overdose can make it hard to breathe. This can be fatal if not treated in time.

If you or someone you love is at risk for an opioid overdose, talk with your doctor or pharmacist about naloxone. Ask them to explain the signs of an overdose and show you and your loved ones how to use naloxone.

In most states, you can get naloxone at a pharmacy without a prescription. Keep the drug on hand so you can easily access it in case of an overdose.

There’s not much known about the safety of Probuphine use during pregnancy. In animal studies, harm to the fetus was seen after pregnant females were given buprenorphine (the active drug in Probuphine). However, animal studies don’t always predict what will happen in humans.

Treatment guidelines recommend that pregnant women with opioid dependence (also called opioid use disorder) receive treatment for this condition. Buprenorphine (the active drug in Probuphine) is recommended as a safe treatment option for pregnant woman.

Risks of Probuphine treatment during pregnancy

One risk of Probuphine treatment during pregnancy is neonatal opioid withdrawal syndrome (NOWS). This is a serious withdrawal syndrome that occurs in babies whose mothers took opioids during pregnancy. But because it’s expected when a pregnant mother is taking a drug such as Probuphine, your baby’s doctor can prepare for it.

Symptoms of NOWS can include:

• diarrhea
• poor feeding
• irritability
• excessive crying

The benefits of treating opioid use disorder in pregnancy should be weighed against the risks of NOWS. The benefits of treatment should also be weighed against the risk of not treating opioid dependence.

What you can do

If you have opioid use disorder and you’re pregnant or considering becoming pregnant, talk with your doctor about your treatment options. Your doctor can discuss the benefits and risks of treatment with you.

If you’re already using Probuphine and you become pregnant, let your doctor know about your pregnancy as soon as possible. But don’t stop taking Probuphine unless your doctor tells you to.

It’s not known exactly how safe Probuphine is to take during pregnancy. If you or your sexual partner can become pregnant, talk with your doctor about your birth control needs while you’re using Probuphine.

Probuphine is probably safe to use as directed by your doctor while you’re breastfeeding.

The American College of Obstetricians and Gynecologists (ACOG) recommends that most women who are on stable treatment for opioid use disorder with a medication, such as Probuphine, breastfeed their children.

Only small amounts of Probuphine pass into breastmilk. However, if you breastfeed while you’re taking Probuphine, you should monitor your child closely for any trouble breathing or increased sleepiness. If your child has either of these side effects, call 911 right away.

It’s also important that you have other options besides breast milk available to feed your child. These options can include items such as baby food (if the child is old enough) or formula milk. You can use these items to feed your child in case you have a relapse (return to using or misusing a drug after you’ve attempted to stop using it). Feeding your child with these other options if you relapse will prevent your child from being exposed to drugs other than Probuphine.

There are some exceptions to the recommendations given by ACOG for breastfeeding. Because of this, it’s important to talk with your doctor about whether it’s safe for you to breastfeed your child while you’re taking Probuphine.

As with all medications, the cost of Probuphine can vary. The actual price you’ll pay depends on your insurance plan and the healthcare facility where you receive your Probuphine doses.

Your insurance company may require you to get prior authorization before they approve insurance coverage for Probuphine. This means that your doctor will need to send a request to your insurance company asking them to cover the drug. Your insurance company will review the request and let you and your doctor know if your plan will cover Probuphine.

If you’re not sure whether you’ll need to get prior authorization for Probuphine, contact your insurance company.

Financial and insurance assistance

If you need financial support to pay for Probuphine, or if you need help understanding your insurance coverage, contact your insurance company.

For more information about cost assistance, visit RxAssist.org. This website lists programs that offer financial assistance for prescription medications.

You’ll receive Probuphine from your healthcare provider. For each dose of the drug, your doctor will insert four 1-inch Probuphine implant rods into your arm.

Probuphine comes as implants that are inserted under the skin of your upper arm. The implants are inserted on the side of your upper arm that’s closest to your body. After the skin heals, you shouldn’t be able to easily see that the implants are in your arm.

Your doctor will insert your Probuphine implants at a healthcare facility. Before inserting the implants, they’ll sterilize (clean to remove germs) your skin over the injection site.

Then your doctor will give you a local anesthetic drug in the area where they plan to inject the Probuphine implants. Local anesthesia is used to stop you from feeling pain during the implant insertion. It’s only used to numb the area directly around the implant site. It won’t make any other areas of your body feel numb.

After the implant area is sterilized (cleaned) and anesthetized (numbed), your healthcare provider will make a small incision (cut) in your skin. They’ll place the implant rods inside the incision, underneath your skin.

A small bandage and pressure dressing will be placed over the area of your implants. The pressure dressing is used to decrease the amount of bruising that happens after the insertion. You should keep this on for about 24 hours. You should keep the smaller bandage on your skin for about 3 to 5 days after the insertion.

After it’s given

Before you leave your insertion appointment, your doctor will give you a patient identification (ID) card. This card shows the date when you received your Probuphine implant and which arm the implant is placed in. You should keep this card with you in your wallet or purse.

After leaving your insertion appointment, you should apply an ice pack to the area of your implant. You can do this for about 40 minutes, every couple of hours. You should do this for the first 24 hours after implant insertion, or longer as needed.

Your doctor will recommend that you to come back to their office a week after your implant was inserted. At this appointment, they’ll check to make sure that you aren’t having any complications from the implant, such as infection or movement of the implant.

When to start using Probuphine

You and your doctor will determine the appropriate time for you to begin treatment with Probuphine. Be sure to keep all appointments with your doctor so they can help you successfully treat your condition.

To help make sure that you don’t miss an appointment, try setting a reminder on your phone.

Probuphine is used to treat opioid dependence, which is now called opioid use disorder by healthcare providers.

What is opioid use disorder?

Opioid use disorder is a chronic (long-term) disorder that causes you to be physically dependent on opioids (strong pain relievers). With dependence, a person’s body needs to have opioids in order for them to feel normal. If the person suddenly stops taking the opioids, they can have opioid withdrawal symptoms. These symptoms can include diarrhea, anxiety, and sweating.

Physical dependence on opioids can be caused by using opioids on a regular basis. It can also be caused by misusing opioids. Misusing a drug means that you’re taking it more often or at a higher dose than your doctor prescribed for you.

What Probuphine does

Probuphine contains the drug buprenorphine, which has similar activity in your body as other opioids. But it also has some differences compared to other opioids.

Buprenorphine is considered a “partial agonist” because it activates (turns on) the same nerve pathways in your brain as other opioids do. Because it’s a partial agonist, it has a “ceiling effect.” This means that the drug’s effects don’t keep increasing as you take higher doses. The effects have a “ceiling” in that they don’t increase past a certain a point.

Because buprenorphine has some of the same effects as other opioids, it helps prevent opioid cravings and withdrawal symptoms. However, it’s less likely that taking buprenorphine will make you feel “high” or lead to misusing the drug than it is if you use other opioids.

How long does it take to work?

Probuphine will begin reducing opioid cravings and preventing withdrawal symptoms within the first day after you’ve had the implant inserted.

Here are answers to some frequently asked questions about Probuphine.

Can my primary care doctor give me the Probuphine implant?

They possibly can. Only specially certified healthcare providers can prescribe and insert Probuphine implants. These providers must complete special training and have experience with certain surgical procedures. Certification for prescribing and inserting Probuphine is regulated by the U.S. federal government.

If you’re considering using Probuphine, talk with your doctor. If they’re not certified to prescribe and insert Probuphine, they can refer you to a healthcare provider who is.

Why do I need to carry a patient ID card while I’m taking Probuphine?

You’ll be given a patient identification (ID) card while you’re using Probuphine so that your other healthcare providers will know that you have the implant.

The ID card will show the date when you had your Probuphine implant inserted. It will also show the date when you should have the implant removed. The card includes the location of your implant so that your healthcare provider can easily and safely remove the implant when needed.

Also, the ID card will let your other healthcare providers know that you have a semipermanent (lasts over a period of time but isn’t permanent) device that releases buprenorphine into your body. This is important because having buprenorphine in your body could affect options for pain treatment that you may need.

For example, if you’re in an accident and you need emergency treatment for pain, your healthcare providers may need to adjust the pain medication they prescribe for you. This is because your body may not respond to pain medications as usual when you’re taking Probuphine.

Also, buprenorphine (the active drug in Probuphine) could interact with other medications you’re taking. Showing your ID card for Probuphine to all of your healthcare providers helps them to safely treat other conditions you may have.

Can Probuphine be used with antidepressants?

It may be used with certain antidepressants. Some antidepressants can increase your risk of serotonin syndrome if taken with Probuphine. Serotonin syndrome is a dangerous condition that’s caused by a buildup of too much serotonin (a brain chemical) in your body.

Symptoms of serotonin syndrome can include:

• fever
• anxiety
• confusion
• muscle spasms
• diarrhea
• seizures

Some antidepressants have a lower risk of serotonin syndrome than others. Talk with your doctor about which antidepressants are safe for you to take if you’re using Probuphine.

Can I use pain medications for fibromyalgia if I’m taking Probuphine?

You may be able to. However, many of the drugs used to treat fibromyalgia, such as gabapentin (Neurontin, Gralise), can interact with Probuphine. Talk with your doctor about which pain medications are safe to take for fibromyalgia while you’re using Probuphine.

This drug comes with several precautions.

FDA warning: Complications from implant placement and removal

This drug has a boxed warning. This is the most serious warning from the Food and Drug Administration (FDA). A boxed warning alerts doctors and patients about drug effects that may be dangerous.

With insertion and removal of Probuphine implants, there is risk of:

• implant movement, which could cause the implant to stick out of your skin or come out of your skin by itself
• nerve damage in your arm
• rare but serious complications from incorrect placement of the implant, such as life-threatening blood clots in your lungs or even death

Because of these risks, insertion and removal of Probuphine implants should only be done by specially certified healthcare providers.

Other precautions

Before taking Probuphine, talk with your doctor about your health history. Probuphine may not be right for you if you have certain medical conditions or other factors affecting your health. These include:

• History of serious allergic reaction. You shouldn’t take Probuphine if you’ve ever had a serious allergic reaction to buprenorphine or to any of the inactive ingredients in Probuphine. If you’re unsure of whether you’ve had a serious allergic reaction to any of the ingredients in Probuphine, talk with your doctor before using this drug.
• Breathing problems. Probuphine can cause respiratory depression (slow and weak breathing). This condition prevents your brain and other organs from getting the oxygen they need. If you have breathing problems, such as COPD or asthma, you may have a higher risk for life-threatening respiratory depression when using Probuphine. If you have breathing problems, talk with your doctor to find out if Probuphine is right for you.
• Liver damage or liver disease. Probuphine shouldn’t be taken by people with moderate or severe liver disease or liver damage. Probuphine can worsen liver problems, including hepatitis C, in people with these conditions. Liver problems can also cause your levels of Probuphine to get too high, which can cause serious side effects or overdose. If you have mild liver problems, your doctor will closely monitor your liver function during Probuphine treatment. If your liver function gets worse or if you have serious side effects due to liver problems, your doctor may recommend that you stop using Probuphine. Talk to your doctor about any liver problems you have to find out whether Probuphine is safe for you.
• Head injury or brain tissue damage. Probuphine can increase the pressure inside of your head, which can lead to serious and permanent brain damage. If you have a history of brain injury or brain tissue damage, Probuphine may not be right for you. Talk with your doctor to find out if Probuphine is safe for you.
• Intestinal damage or intestinal disease. Probuphine can cause intestinal side effects, such as constipation. These side effects can make it harder for your healthcare provider to treat intestinal problems you may have. If you have problems with your intestines, talk with your doctor about whether Probuphine is right for you.
• Bile duct damage or bile duct disease. Probuphine can increase pressure in your bile duct tract (an area of your body that includes your bile ducts, gallbladder, and liver). If you have problems with your bile duct, talk with your doctor about whether Probuphine is right for you.
• Dependence on opioids other than buprenorphine. Probuphine can cause severe opioid withdrawal symptoms if it’s taken by someone who is dependent on an opioid other than buprenorphine. If you’re taking opioids other than buprenorphine, Probuphine may not be right for you. Talk with your doctor to discuss an appropriate treatment plan.
• Pregnancy. It’s not known exactly how safe Probuphine is during pregnancy. For more information, please see the “Probuphine and pregnancy” section above.
• Breastfeeding. Taking Probuphine while breastfeeding is probably safe for most people. But talk with your doctor before breastfeeding while you’re using Probuphine. For more information, please see the “Probuphine and breastfeeding” section above.

Note: For more information about the potential negative effects of Probuphine, see the “Probuphine side effects” section above.