Subutex Side Effects Center

Last updated on RxList: 2/7/2022
Subutex Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Subutex?

Subutex (buprenorphine) is an opioid (narcotic) medication used to treat narcotic addiction. The brand name Subutex is discontinued, but generic versions may be available.

What Are Side Effects of Subutex?

Common side effects of Subutex include:

Dosage for Subutex

Subutex sublingual tablet is administered sublingually as a single daily dose.

What Drugs, Substances, or Supplements Interact with Subutex?

Subutex may interact with

    • other narcotics,
    • sedatives,
    • tranquilizers,
    • sleeping pills,
    • muscle relaxers,
    • or other medicines that can make you sleepy or slow your breathing,
    • conivaptan,
    • imatinib,
    • isoniazid,
    • nefazodone,
    • antibiotics,
    • antifungals,
    • heart or blood pressure medications,
    • or HIV/AIDS medicines

    Tell your doctor all medications and supplements you use.

    Subutex During Pregnancy and Breastfeeding

    It is unknown if Subutex will harm a fetus. This drug may cause addiction or withdrawal symptoms in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant before using Subutex. This drug can pass into breast milk and may harm a nursing baby. Do not breastfeed while using Subutex. Withdrawal symptoms may occur if you suddenly stop taking this medication.

    Additional Information

    Our Subutex (buprenorphine) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

    This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Prescription Drug Abuse: Addiction, Health Risks, and Treatments See Slideshow
Subutex Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Call your doctor at once if you have:

  • opioid withdrawal symptoms--shivering, goose bumps, increased sweating, feeling hot or cold, runny nose, watery eyes, diarrhea, muscle pain;
  • noisy breathing, sighing, shallow breathing, breathing that stops during sleep;
  • slow heartbeat or weak pulse;
  • a light-headed feeling, like you might pass out;
  • chest pain, trouble breathing;
  • low cortisol levels-- nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness; or
  • liver problems--nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Common side effects may be more likely to occur, such as:

  • constipation, nausea, vomiting;
  • headache;
  • increased sweating;
  • sleep problems (insomnia); or
  • pain anywhere in your body.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Subutex Professional Information

SIDE EFFECTS

The following serious adverse reactions are described elsewhere in the labeling:

  • Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
  • Respiratory and CNS Depression [see WARNINGS AND PRECAUTIONS]
  • Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
  • Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
  • Opioid Withdrawal [see WARNINGS AND PRECAUTIONS]
  • Hepatitis, Hepatic Events [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
  • Elevation of Cerebrospinal Fluid Pressure [see WARNINGS AND PRECAUTIONS]
  • Elevation of Intracholedochal Pressure [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of SUBUTEX was supported by clinical trials using SUBUTEX, SUBOXONE (buprenorphine/naloxone sublingual tablet) and other trials using buprenorphine sublingual solutions. In total, safety data were available from 3214 opioid–dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction.

Few differences in adverse event profile were noted between SUBUTEX or buprenorphine administered as a sublingual solution.

The following adverse events were reported to occur by at least 5% of patients in a 4–week study (Table 1).

Table 1. Adverse Events ≥ 5% by Body System and Treatment Group in a 4–week study

Body System / Adverse Event (COSTART Terminology) N (%) N (%)
SUBUTEX 16 mg/day N=103 Placebo N=107
Body as a Whole
Asthenia 5 (4.9%) 7 (6.5%)
Chills 8 (7.8%) 8 (7.5%)
Headache 30 (29.1%) 24 (22.4%)
Infection 12 (11.7%) 7 (6.5%)
Pain 19 (18.4%) 20 (18.7%)
Pain Abdomen 12 (11.7%) 7 (6.5%)
Pain Back 8 (7.8%) 12 (11.2%)
Withdrawal Syndrome 19 (18.4%) 40 (37.4%)
Cardiovascular System
Vasodilation 4 (3.9%) 7 (6.5%)
Digestive System
Constipation 8 (7.8%) 3 (2.8%)
Diarrhea 5 (4.9%) 16 (15.0%)
Nausea 14 (13.6%) 12 (11.2%)
Vomiting 8 (7.8%) 5 (4.7%)
Nervous System
Insomnia 22 (21.4%) 17 (15.9%)
Respiratory System
Rhinitis 10 (9.7%) 14 (13.1%)
Skin and Appendages
Sweating 13 (12.6%) 11 (10.3%)

The adverse event profile of buprenorphine was also characterized in the dose–controlled study of buprenorphine solution, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose–controlled study.

Table 2. Adverse Events (≥ 5%) by Body System and Treatment Group in a 16–week Study

Body System /Adverse Event (COSTART Terminology) Buprenorphine Dose*
Very Low* (N=184) Low* (N=180) Moderate* (N=186) High* (N=181) Total* (N=731)
N (%) N (%) N (%) N (%) N (%)
Body as a Whole
Abscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%)
Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%)
Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%)
Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%)
Flu Syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%)
Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%)
Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%)
Injury Accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%)
Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%)
Pain Back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%)
Withdrawal Syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%)
Digestive System
Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%)
Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%)
Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%)
Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%)
Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%)
Nervous System
Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%)
Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%)
Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%)
Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%)
Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%)
Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%)
Respiratory System
Cough Increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%)
Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 26 (4%)
Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%)
Skin and Appendages
Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%)
Special Senses
Runny Eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%)
*Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes:
"Very low" dose (1 mg solution) would be less than a tablet dose of 2 mg
"Low" dose (4 mg solution) approximates a 6 mg tablet dose
"Moderate" dose (8 mg solution) approximates a 12 mg tablet dose
"High" dose (16 mg solution) approximates a 24 mg tablet dose

Postmarketing Experience

The following adverse reactions have been identified during post approval use of buprenorphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most frequently reported post–marketing adverse events with SUBUTEX not observed in clinical trials, excluding drug exposure during pregnancy, was drug misuse or abuse.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life–threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in SUBUTEX.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Local reactions: Glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis.

DRUG INTERACTIONS

Table 3 includes clinically significant drug interactions with SUBUTEX.

Table 3. Clinically Significant Drug Interactions

Benzodiazepines or other Central Nervous System (CNS) Depressants
Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.
Intervention: Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or CNS depressant or decreasing to the lowest effective dose may be appropriate.

Before co–prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non–pharmacologic treatments [see WARNINGS AND PRECAUTIONS].

If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in treatment for opioid use disorder [see WARNINGS AND PRECAUTIONS].
Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids.
Inhibitors of CYP3A4
Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of SUBUTEX is achieved.

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see CLINICAL PHARMACOLOGY], potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine.

Intervention: If concomitant use is necessary, consider dosage reduction of SUBUTEX until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals.

If a CYP3A4 inhibitor is discontinued, consider increasing the SUBUTEX dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

Examples: Macrolide antibiotics (e.g., erythromycin), azole–antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir)
CYP3A4 Inducers
Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see CLINICAL PHARMACOLOGY], potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine.

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression.

Intervention: If concomitant use is necessary, consider increasing the SUBUTEX dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

If a CYP3A4 inducer is discontinued, consider SUBUTEX dosage reduction and monitor for signs of respiratory depression.

Examples: Rifampin, carbamazepine, phenytoin
Antiretrovirals: Non–nucleoside reverse transcriptase inhibitors (NNRTIs)
Clinical Impact: Non–nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects.
Intervention: Patients who are on chronic SUBUTEX treatment should have their dose monitored if NNRTIs are added to their treatment regimen.
Examples: efavirenz, nevirapine, etravirine, delavirdine
Antiretrovirals: Protease inhibitors (PIs)
Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post–marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly.
Intervention: Monitor patients taking SUBUTEX and atazanavir with and without ritonavir, and reduce dose of SUBUTEX if warranted.
Examples: atazanavir, ritonavir
Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs)
Clinical Impact: Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected.
Intervention: None
Serotonergic Drugs
Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue SUBUTEX if serotonin syndrome is suspected.
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5–HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Intervention: The use of SUBUTEX is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Examples: phenelzine, tranylcypromine, linezolid
Muscle Relaxants
Clinical Impact: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention: Monitor patients receiving muscle relaxants and SUBUTEX for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of SUBUTEX and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, strongly consider prescribing naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].
Diuretics
Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
Clinical Impact: The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when SUBUTEX is used concomitantly with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

SUBUTEX contains buprenorphine, a Schedule III controlled substance under the Controlled Substances Act.

Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in the treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Abuse

Buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. Healthcare professionals should contact their state professional licensing board or state–controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Patients who continue to misuse, abuse, or divert, buprenorphine products or other opioids should be provided or referred for more intensive and structured treatment.

Abuse of buprenorphine poses a risk of overdose and death. This risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines.

The healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed.

Proper assessment of the patient, proper prescribing practices, periodic re–evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs.

Dependence

Buprenorphine is a partial agonist at the mu–opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see WARNINGS AND PRECAUTIONS].

Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Subutex (Buprenorphine)

© Subutex Patient Information is supplied by Cerner Multum, Inc. and Subutex Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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