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Probuphine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on March 28, 2023.

1. How it works

  • Probuphine is a brand (trade) name for a buprenorphine implant that may be used for the maintenance treatment of opioid dependence.
  • Probuphine (buprenorphine) is a partial opioid agonist which means it binds to and activates opioid receptors (particularly mu receptors) but less strongly than full agonists do. This means it can reduce cravings and withdrawal symptoms in a person with an opioid use disorder without producing euphoria. Some forms of buprenorphine can be used to provide pain relief because activating mu opioid receptors also relieves pain.
  • Probuphine belongs to the class of medicines known as narcotic analgesics. It may also be called an opioid analgesic.
  • Probuphine has been discontinued. This information is kept for historical purposes only.

2. Upsides

  • Probuphine may be used for the maintenance treatment of opioid dependence in people who have already demonstrated prolonged clinical stability on low-to-moderate dosages (8mg/day or less) of sublingual/buccal buprenorphine dosage forms, such as Subutex or Suboxone.
  • Acceptable dosages of sublingual/buccal buprenorphine that allow Probuphine to be considered include Subutex 8mg or less, Suboxone 8mg/2mg or less, Bunavail 4.2mg/0.7mg or less, Zubsolv 5.7mg/1.4mg or less. People should not be tapered to a lower dosage of any one of these medications for the sole purpose of transitioning to Probuphine.
  • Probuphine is used as part of a complete treatment program that includes counseling and psychosocial support.
  • Probuphine is inserted just under the skin of the upper arm (8 to 10cm from the medial epicondyle) by a healthcare provider certified to perform buprenorphine insertions.
  • Probuphine lasts for 6 months which eliminates the need for daily dosing of sublingual tablets or once-monthly administration of buprenorphine injection.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Gastrointestinal effects (such as nausea, vomiting, upper abdominal pain, or constipation), dental conditions, pain, tiredness, headaches, depression, and implant site-related side effects (such as pain, itching, infection, or swelling) are the most common side effects reported.
  • Respiratory depression (severe difficulty with breathing) can also occur with Probuphine. More likely to occur in the elderly, debilitated, or those with pre-existing breathing problems.
  • May cause sleepiness or dizziness and affect a person's ability to drive or operate machinery. Avoid alcohol.
  • May also cause vertigo, adrenal suppression, and serious liver effects. Liver function may need monitoring.
  • May cause a severe lowering of blood pressure, or a sudden drop in blood pressure when going from sitting to standing.
  • Rare but serious complications such as nerve damage and migration have occurred because of incorrect Probuphine implant insertion. Because of this Probuphine is only available through a restricted program called the Probuphine REMS Program. This involves a live training program on insertion and removal procedures and certification once competency has been demonstrated, meaning that Probuphine can only be inserted and removed by a healthcare provider certified to perform insertions.
  • Probuphine is not suitable for people that are new to opioid dependence treatment or for those who have not achieved prolonged clinical stability while being maintained on sublingual/buccal buprenorphine 8mg per day or less.
  • May only be prescribed by healthcare providers that meet certain qualifying requirements and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe or dispense this product for the treatment of opioid dependence. These healthcare providers have been assigned a unique identification number that must be written on every prescription.
  • The insertion site should be examined one week following the insertion for signs of infection, problems with wound healing, or evidence of implant extrusion from the skin.
  • Probuphine implants need to be removed and replaced after 6 months. New implants should be inserted in the other arm as long as it is an area that has not been previously used. If there is a delay between removing old implants and inserting new ones, sublingual buprenorphine may be given as cover.
  • Probuphine is only recommended to be inserted once into each arm. Repeated reinsertions into previously used administration sites have not been studied. After 6 months of implants in one arm and 6 months of implants in the other arm, people should be transitioned back to sublingual buprenorphine for continued treatment.
  • Patients who require or request regular supplemental dosing with sublingual/buccal buprenorphine should be reevaluated because the amount of buprenorphine delivered by Probuphine may not be enough for them to achieve stable maintenance. The occasional supplemental dose is considered OK.
  • Probuphine has a high potential for abuse, similar to other opioid analgesics. The risk may be higher in those with a personal or family history of substance or alcohol abuse or with a psychiatric disorder.
  • Probuphine may be addictive and cause psychological dependence and withdrawal symptoms, particularly when used for long periods.
  • May interact with several other drugs including other opioids, benzodiazepines, and other central nervous system depressants resulting in profound sedation, respiratory depression, and sometimes death. May also interact with drugs metabolized through CYP hepatic enzyme systems (such as CYP3A4 or CYP2D6) or drugs that also release serotonin (such as antidepressants, antipsychotics, and tramadol). There is a risk of heart rhythm disorders (such as QT prolongation) associated with Probuphine, particularly when used with other drugs that prolong the QT interval.
  • May not be suitable for some people such as those with liver disease, the elderly or frail, with a history of drug or alcohol abuse, with psychiatric disorders, previous head injury or raised intracranial pressure, a history of seizure disorders, with certain gastrointestinal conditions, respiratory disease, physically dependent on full agonists, or certain other concomitant conditions. Use during pregnancy may cause withdrawal symptoms in the newborn baby.
  • Probuphine should not be stopped suddenly. Sublingual/buccal buprenorphine should be used if implants are removed without replacement or on discontinuing Probuphine because of the risk of withdrawal.
  • Probuphine is not available as a generic.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Probuphine is a buprenorphine implant that lasts for 6 months and may be considered in people who are stable on sublingual/buccal forms of buprenorphine providing they meet certain other criteria. Insertion and removal of Probuphine must be done by a certified healthcare provider and it is not recommended to be inserted more than once into each arm (at least 6 months apart). Probuphine has been discontinued in the United States.

5. Tips

  • Probuphine must be inserted and removed by a qualified and certified healthcare provider. Probuphine is only recommended to be inserted twice (once in each arm). This is done using a minor surgical procedure.
  • Your healthcare provider will cover the area where Probuphine was inserted with two bandages. The first is left on for 24 hours and the bottom one for three to five days.
  • To qualify for Probuphine, you must demonstrate prolonged clinical stability. To determine this, your doctor will assess several different factors, such as how long you have been free from illicit opioid drug use, the stability of your living environment, your participation in recommended behavioral or peer support programs, your compliance with clinic visits, and your social support system.
  • Your healthcare provider will give you a Patient identification card to carry with you. This will record the date the implants were inserted and the date they should be removed. Schedule an appointment with your healthcare provider before the removal date.
  • Even though a Probuphine implant lasts for 6 months, you will need to be seen at least every month for counseling and psychosocial support.
  • If you notice that part of the implant has come out of your skin, ring your healthcare provider as soon as possible and schedule an appointment. Place the expelled part of the implant into a plastic bag and take it with you. Your healthcare provider will instruct you on what will happen next. Do not try to remove the implants yourself.
  • Probuphine implants may only be inserted once into each arm (at least six months apart). There is no experience with reinserting them into an arm that has previously had an implant. Once you have finished your course of Probuphine you will need to be transferred onto another form of buprenorphine.
  • While you have Probuphine inserted you should not need any more than the occasional supplemental dose of buprenorphine. If you require more regular dosing of supplemental buprenorphine then you should see your healthcare provider because Probuphine may not be the right dosage form for you.
  • When used to treat drug addiction, it is important that you take advantage of any social support and counseling services offered to you as withdrawal from opioids is a long and often difficult process and a successful outcome is dependent upon a multi-targeted approach.
  • Always talk to your doctor or pharmacist before buying anything over-the-counter to check if it is compatible with Probuphine.
  • Tell your doctor if you experience any difficulty with breathing or shortness of breath after Probuphine has been inserted, especially within the first 24 to 72 hours of initiating therapy. Also tell them if you have any bleeding or signs of infection at the insertion site, an allergic reaction, or numbness or weakness in your arm.
  • Probuphine should not be removed suddenly without any buprenorphine cover. This helps to minimize any withdrawal symptoms which include restlessness, runny nose and eyes, muscle pain, and insomnia.
  • Rise carefully from a sitting to a standing position to minimize blood pressure-lowering effects from Probuphine which may result in dizziness increasing your risk of falls.
  • Probuphine may cause constipation. Talk to your doctor about taking laxatives as a preventive against constipation if you are prescribed Probuphine.
  • Probuphine may cause androgen deficiency that may cause symptoms such as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. Talk to your doctor if this happens to you.
  • Always talk to your doctor or pharmacist before buying anything over-the-counter to check if it is compatible with Probuphine. If Probuphine is administered with other drugs that also release serotonin, such as tramadol, lithium, or antidepressants, a condition called serotonin syndrome may develop. Symptoms include agitation or restlessness, sweating, diarrhea, headache, confusion, rapid heart rate, high blood pressure, dilated pupils, loss of muscle coordination, twitching muscles, or muscle rigidity. See your doctor immediately.
  • If you are a woman of childbearing age you should use adequate contraception to ensure you do not become pregnant while Probuphine is inserted. If you inadvertently become pregnant, tell your doctor straight away as there is a risk your baby may be born with neonatal withdrawal syndrome which will need to be treated. Do not breastfeed while taking Probuphine.
  • Do not drive or operate machinery if you are prescribed Probuphine because it may impair your ability to perform these tasks unless you are tolerant to its effects.
  • You should not drink alcohol while you are prescribed Probuphine because it may impair your ability to concentrate and also increase the risk of side effects such as respiratory depression.

6. Response and effectiveness

  • Each dose consists of four Probuphine implants that are inserted just under the skin on the inner side of the upper arm.
  • Each Probuphine implant contains 74.2mg of buprenorphine (equivalent to 80mg of buprenorphine hydrochloride). The rods are 26mm in length and 2.5mm in diameter.
  • 63% of people assigned to Probuphine only had no evidence of illicit drug use throughout a 6-month period compared to 64% of people assigned sublingual buprenorphine.
  • Report any failure to locate non-palpable implants using MRI or ultrasound to 1-844-859-6341.

7. Interactions

Medicines that interact with Probuphine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Probuphine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Probuphine include:

  • anticholinergic drugs, such as benztropine
  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that inhibits or induces CYP3A4. Inhibitors include erythromycin, ketoconazole, and ritonavir. Inducers include rifampin, carbamazepine, or phenytoin.
  • any medication that may cause drowsiness, such as amphetamines, first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, methadone, or morphine)
  • benzodiazepines (eg, diazepam, lorazepam) or other central nervous system depressants, such as barbituates or sedatives
  • diuretics, such as bendofluazide or furosemide
  • HIV medications such as atazanavir, efavirenz, nevirapine, or ritonavir
  • mixed agonists/antagonists and partial agonist opioids, such as butorphanol, nalbuphine, or pentazocine
  • muscle relaxants, such as methocarbamol, cyclobenzaprine, carisoprodol, metaxalone, tizanidine, or baclofen.
  • naloxone and naltrexone
  • QT-prolonging medications such as amiodarone and flecainide
  • rifampin
  • St. John's Wort.

Any medication that releases serotonin (such as amitriptyline, tramadol, or St. John's Wort) may interact with Probuphine and cause serotonin syndrome, a potentially fatal condition that occurs when levels of serotonin get too high in your body. Symptoms can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever, and seizures).

Avoid drinking alcohol or taking illegal or recreational drugs while taking Probuphine.

Note that this list is not all-inclusive and includes only common medications that may interact with Probuphine. You should refer to the prescribing information for Probuphine for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Probuphine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: March 28, 2023.