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Probuphine Side Effects

Generic name: buprenorphine

Medically reviewed by Philip Thornton, DipPharm. Last updated on Apr 19, 2023.

Note: This document contains side effect information about buprenorphine. Some dosage forms listed on this page may not apply to the brand name Probuphine.

Applies to buprenorphine: film, tablet. Other dosage forms:

Warning

Buccal mucosa route (Film)

Addiction, Abuse, and MisuseBuprenorphine exposes 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 buprenorphine, and monitor all patients regularly for the development of these behaviors or conditions.Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to: complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacists, and consider other tools to improve patient, household, and community safety.Life-Threatening Respiratory DepressionSerious, life-threatening, or fatal respiratory depression may occur with use of buprenorphine. Monitor for respiratory depression, especially during initiation of buprenorphine or following a dose increase. Misuse or abuse of buprenorphine by chewing, swallowing, snorting or injecting buprenorphine extracted from the buccal film will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death.Accidental ExposureAccidental exposure to even one dose of buprenorphine, especially by children, can result in a fatal overdose of buprenorphine.Neonatal Opioid Withdrawal SyndromeProlonged use of buprenorphine 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.Risks from Concomitant Use with Benzodiazepines or Other CNS DepressantsReserve concomitant prescribing of buprenorphine 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.

Serious side effects of Probuphine

Along with its needed effects, buprenorphine (the active ingredient contained in Probuphine) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking buprenorphine:

Less common

Rare

Incidence not known

Get emergency help immediately if any of the following symptoms of overdose occur while taking buprenorphine:

Symptoms of overdose

Other side effects of Probuphine

Some side effects of buprenorphine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

Rare

For Healthcare Professionals

Applies to buprenorphine: buccal film, compounding powder, injectable solution, subcutaneous solution extended release, subdermal implant, sublingual tablet, transdermal film extended release.

Cardiovascular

Common (1% to 10%): Circulatory collapse, circulatory disorders, ECG prolonged QT, flushing, hot flush, hypertension, hypotension, orthostatic hypotension, palpitations, tachycardia, vasodilatation, vasodilation

Uncommon (0.1% to 1%): Angina pectoris, bradycardia, cyanosis, heat stroke, myocardial infarction, pallor, second degree atrioventricular block

Rare (0.01% to 0.1%): Hot flushes

Frequency not reported: Atrial fibrillation, coronary artery disease, fainting, fall in blood pressure, increased blood pressure, prolonged QTc, Wenckebach block

Postmarketing reports: Heart rate/rhythm disorders, hypotension, orthostatic hypotension

Circulatory disorders included hypotension and rarely, circulatory collapse.

Dermatologic

Very common (10% or more): Sweating (up to 13%), erythema, hyperhidrosis/sweating, pruritus

Common (1% to 10%): Cellulitis, diaphoresis, exanthema, excoriation, generalized pruritus, laceration, rash, subcutaneous abscess, urticaria

Uncommon (0.1% to 1%): Acne, alopecia, dry skin, exfoliative dermatitis, macular rash, scratch, skin lesion, skin mass

Very rare (less than 0.01%): Pustules, vesicles

Frequency not reported: Angioedema (Quincke's edema)/angioneurotic edema, contact dermatitis, skin discoloration, urticaria/hives

Postmarketing reports: Angioneurotic edema, hyperhidrosis, pruritus, rash

Endocrine

Frequency not reported: Decreased blood testosterone

Opioids:

-Postmarketing reports: Adrenal insufficiency, androgen deficiency

Cases of adrenal insufficiency have been reported with opioid use, more often when used beyond 1 month. Cases of androgen deficiency have occurred with prolonged opioid use.

Gastrointestinal

According to some authorities, females reported nausea and vomiting 10% to 15% more frequently than males.

Dental decay included caries, tooth fracture, and tooth loss.

Cases of dental caries, some severe (i.e., tooth fracture, tooth loss), have been reported after the use of transmucosal buprenorphine-containing products. Reported events included cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss.

Very common (10% or more): Nausea (up to 50%), constipation (up to 14%), abdominal pain (up to 11.7%), diarrhea (up to 10.3%), dry mouth, vomiting

Common (1% to 10%): Dyspepsia, flatulence, gastroenteritis, gastrointestinal disorder, increased lipase, oral herpes, stomach discomfort, tooth abscess, tooth disorder, tooth infection, toothache, upper abdominal pain, viral gastroenteritis

Uncommon (0.1% to 1%): Tongue discoloration, mouth ulceration

Rare (0.01% to 0.1%): Diverticulitis, dysphagia, ileus, pyrosis/heartburn

Very rare (less than 0.01%): Retching

Frequency not reported: Abdominal discomfort, abdominal distention

Postmarketing reports: Dental decay, nausea, vomiting

Genitourinary

Common (1% to 10%): Dysmenorrhea, erectile dysfunction, urinary aberration, urinary retention, urinary tract infection

Uncommon (0.1% to 1%): Albuminuria, amenorrhea, dysuria, ejaculation disorder, hematuria, intermenstrual bleeding, menorrhagia, micturition disorders, urinary hesitation, urinary incontinence, vaginal infection

Rare (0.01% to 0.1%): Decreased erection, sexual dysfunction

Postmarketing reports: Urinary retention

Hematologic

Common (1% to 10%): Anemia, lymphadenopathy

Uncommon (0.1% to 1%): Leukocytosis, leukopenia, thrombocytopenia

Hepatic

Increased ALT (greater than 3 times the upper limit of normal [3 x ULN]) and increased AST (greater than 3 x ULN) have been reported in up to 12.4% and up to 11.4% of patients, respectively.

Increased hepatic enzymes included increased hepatic enzymes, abnormal liver function test, and elevated ALT, AST, GGT, alkaline phosphatase, and/or bilirubin.

The spectrum of hepatic abnormalities ranged from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy.

Very common (10% or more): Increased ALT (12.4%), increased AST (up to 11.4%)

Common (1% to 10%): Abnormal liver enzymes, abnormal liver function tests, increased GGT, increased hepatic enzymes

Uncommon (0.1% to 1%): Hepatic necrosis, hepatitis

Rare (0.01% to 0.1%): Biliary colic

Frequency not reported: Abnormal hepatic function, abnormal liver function test, acute hepatitis, cholecystitis, cytolytic hepatitis, hepatic abnormalities, hepatitis with jaundice, hepatorenal syndrome, increased intracholedochal pressure, increased transaminases, jaundice

Postmarketing reports: Elevated hepatic transaminases, hepatic encephalopathy, hepatic failure, hepatic necrosis, hepatitis, hepatorenal syndrome, jaundice

Hypersensitivity

Common (1% to 10%): Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction

Rare (0.01% to 0.1%): Anaphylactic reaction

Very rare (less than 0.01%): Serious allergic reactions

Frequency not reported: Anaphylactic shock, anaphylactoid reaction, drug hypersensitivity

Postmarketing reports: Anaphylactic shock, anaphylaxis

Cases of acute and chronic hypersensitivity to this drug have been reported in clinical trials and during postmarketing experience. The most common signs/symptoms included rashes, hives, and pruritus; cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported.

Allergic reaction included oropharyngeal swelling and swollen tongue.

Serious allergic reactions have been reported; in some cases, delayed allergic reactions occurred with marked signs of inflammation.

Local

Application site reaction included erythema, edema, pruritus, or rash at the application site.

Application site skin reactions included common signs/symptoms of contact dermatitis (irritative/allergic), erythema, edema, pruritus, rash, vesicles, and pain/burning sensation at the application site. In some cases, late-onset local allergic reactions (allergic contact dermatitis) occurred with marked signs of inflammation.

In rare cases, severe application site skin reactions with signs of marked inflammation (including burn, discharge, and vesicles) have occurred.

Cases of injection site abscess, ulceration, and necrosis have been reported after treatment initiation. Some cases required debridement and antibiotic treatment.

Very common (10% or more): Administration site reactions (up to 20.7%), application site pruritus (up to 15%), implant site pain (up to 13%), implant site pruritus (up to 12%), implant site erythema (10.4%), application site erythema, application site reaction, application site skin reactions

Common (1% to 10%): Application site irritation, application site rash, implant site edema, implant site hematoma, implant site hemorrhage, injection site bruising, injection site erythema, injection site induration, injection site inflammation, injection site mass, injection site pain, injection site pruritus, injection site reaction, injection site swelling, injection site ulcer

Uncommon (0.1% to 1%): Injection site cellulitis, injection site discomfort, injection site edema, injection site infection, injection site urticaria, local swelling

Rare (0.01% to 0.1%): Administration site reactions

Frequency not reported: Application site dermatitis, application site skin discoloration

Postmarketing reports: Injection site abscess, injection site mass, injection site necrosis, injection site ulceration

Metabolic

Cases of hypoglycemia have been reported in patients taking opioids; most reports were in those with at least 1 predisposing risk factor (e.g., diabetes).

Common (1% to 10%): Anorexia, decreased appetite/appetite loss, increased blood glucose

Uncommon (0.1% to 1%): Dehydration, hyperglycemia, hyperlipidemia, hypoglycemia

Opioids:

-Postmarketing reports: Hypoglycemia

Musculoskeletal

Very common (10% or more): Back pain (up to 16%)

Common (1% to 10%): Arthralgia, bone pain, increased blood creatine phosphokinase, joint swelling, leg cramps, ligament sprain, muscle spasms, muscle twitching, muscular weakness, musculoskeletal pain, myalgia, neck pain, pain in extremity

Uncommon (0.1% to 1%): Arthritis, muscle cramps, muscle strain

Frequency not reported: Ankle fracture, muscle aches, muscle weakness, osteoarthritis

Nervous system

Very common (10% or more): Headache (up to 34%), dizziness (up to 15%), somnolence (up to 13%), drowsiness, sedation, sleep, vertigo

Common (1% to 10%): Dysgeusia/taste disturbance, hypertonia, hypoesthesia, lethargy, migraine, paresthesia, speech disorders, syncope, tremor

Uncommon (0.1% to 1%): Abnormal coordination, amnesia, coma, concentration impairment, disturbance in attention, dysarthria, dysgeusia/parageusia, exhaustion, hyperkinesia, impaired speech, lack of muscle coordination, memory impairment, paresthesia (e.g., pricking/burning skin sensation), procedural dizziness, seizure, slurred speech, tinnitus

Rare (0.01% to 0.1%): Balance disorder, convulsions, disequilibrium, impaired concentration, numbness, seizures, speech disorder

Very rare (less than 0.01%): Involuntary muscle contractions, muscle fasciculation

Frequency not reported: Cerebrovascular accident, depressed level of consciousness, dysgeusia, gait disturbance, hyperalgesia, loss of consciousness, mental impairment, postural dizziness, sleep apnea syndrome, sleepiness, transient ischemic attack

Postmarketing reports: Coma, convulsions, dizziness, headache, neonatal tremor, somnolence, vertigo

Opioids:

-Postmarketing reports: Serotonin syndrome, hyperalgesia, allodynia

According to some authorities, females reported dizziness and headache 10% to 15% more frequently than males.

In clinical studies involving 1133 patients, sedation occurred in about two-thirds of the patients.

Serotonin syndrome (a potentially life-threatening condition) has been reported during concomitant use of opioids with serotonergic drugs.

Hyperalgesia and allodynia have been reported with opioid therapy of any duration.

Ocular

Common (1% to 10%): Amblyopia, lacrimal disorder, lacrimation disorders, miosis, mydriasis, runny eyes, tears disturbance

Uncommon (0.1% to 1%): Blurred vision, conjunctivitis, diplopia, dry eye, visual impairment

Rare (0.01% to 0.1%): Eyelid edema, visual disturbance

Frequency not reported: Visual abnormalities

Postmarketing reports: Miosis

Other

The most common adverse events reported were those related to withdrawal symptoms (e.g., abdominal pain, headache, pain, diarrhea, nausea, muscle aches, anxiety, sweating).

Asthenic conditions included muscle weakness, lethargy, fatigue, and malaise.

Accidental injury included fall.

Withdrawal symptoms included agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor, and gastrointestinal disorders.

During treatment of opioid use disorder, cases of drug withdrawal reactions consistent with insufficient drug dosing have been reported; cases often occurred at or after 2 weeks of treatment initiation and resolved upon dose increase.

In cases of IV or intentional misuse, local reactions (e.g., cellulitis, abscess) that were sometimes septic, potentially serious acute hepatitis, pneumonia, endocarditis, and other serious infections have been reported.

Very common (10% or more): Pain (up to 26%), withdrawal syndrome (up to 24%), infection (up to 22%), asthenia (up to 16%), drug withdrawal syndrome, tiredness

Common (1% to 10%): Abscess, accidental injury, accidental overdose, asthenic conditions, chest pain, chills, contusion, decreased weight, ear pain, edema, fall, fatigue, fever, increased weight, injury, limb injury, malaise, neonatal drug withdrawal syndrome, peripheral edema, pyrexia, road traffic accident, viral infection, weight loss

Uncommon (0.1% to 1%): Accidental injury (including fall), chills/cold, face edema, feeling cold, hypothermia, influenza-like illness, noncardiac chest pain, rigors, warmth, weariness

Rare (0.01% to 0.1%): Withdrawal symptoms

Very rare (less than 0.01%): Thoracic pain

Frequency not reported: Drug ineffective, drug interactions, drug tolerance, weakness

Postmarketing reports: Deaths, decreased weight, drug ineffective, drug interaction, drug misuse, drug withdrawal reactions, drug withdrawal syndrome, fatigue, fetal disorders, IV/intentional misuse, neonatal withdrawal syndrome, peripheral edema

Buprenorphine-naloxone sublingual tablets:

-Postmarketing reports: Peripheral edema

Psychiatric

Very common (10% or more): Insomnia (up to 28%), anxiety (up to 14%), depression (up to 13%)

Common (1% to 10%): Abnormal thinking, agitation, confusion, decreased libido, hallucinations, hostility, medical dependence, nervousness, paranoia

Uncommon (0.1% to 1%): Abnormal dreaming, affect lability, aggression, apathy, confusional state, depersonalization, disorientation, dreaming, euphoria/euphoric mood, euphoric mood, euphoric mood/euphoria, nightmare, psychosis, psychotic disorder, restlessness, sleep disorder

Rare (0.01% to 0.1%): Dysphoria, psychomimetic effects (e.g., hallucinations, anxiety, nightmares)

Very rare (less than 0.01%): Dependence, mood swings

Frequency not reported: Confusional state/confusion, depressed mood, drug dependence, mental status changes, psychotic disorder/psychosis

Postmarketing reports: Confusional state, drug abuse, drug dependence, hallucinations, neonatal feeding disorder

Renal

Uncommon (0.1% to 1%): Increased blood creatinine, nephrolithiasis

Respiratory

Very common (10% or more): Rhinitis (up to 15%), influenza syndrome (up to 10.2%)

Common (1% to 10%): Asthma, bronchitis, cough, dyspnea, hypoventilation, increased cough, influenza, nasal congestion, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngolaryngeal pain, pneumonia, sinus congestion, sinusitis, upper respiratory tract infection, yawning

Uncommon (0.1% to 1%): Apnea, asthma aggravated, hiccups, hyperventilation, hypoxia, respiratory depression, wheezing

Rare (0.01% to 0.1%): Respiratory failure

Frequency not reported: Abnormal respiration, acute sinusitis, bronchospasm, respiratory distress, rhinorrhea

Postmarketing reports: Asphyxia, bronchospasm, hypoventilation, respiratory depression

Opioids:

-Frequency not reported: Respiratory depression, sleep-related breathing disorders (including central sleep apnea, sleep-related hypoxemia)

Serious, life-threatening, or fatal respiratory depression has been reported with opioid use, even when used as recommended.

Frequently asked questions

Further information

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

Some side effects may not be reported. You may report them to the FDA.

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