Buprenorphine

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Generic Name: Buprenorphine Brand Name(s): Generics only. No brands available. Avability: Rx Pregnancy Category: N

Uses

What is Buprenorphine used for?

Buprenorphine is used to treat opioid (narcotic) dependence/addiction. Buprenorphine belongs to a class of drugs known as mixed opioid agonist-antagonists. It helps prevent withdrawal symptoms caused by stopping other opioids. It is used as part of a complete treatment program for drug abuse (such as compliance monitoring, counseling, behavioral contract, lifestyle changes).

How should I take Buprenorphine?

Your doctor will place 4 medicated implants under the skin of your upper arm. Each implant releases buprenorphine into your blood slowly and continuously over 6 months. After 6 months, your doctor will remove the implants. Your doctor may insert new implants in your other arm if you need to continue treatment. Follow your doctor’s instructions for proper care of the place where the implants were inserted or removed. Consult your doctor for details.

If you suddenly stop using this medication, you may have withdrawal symptoms (such as restlessness, watering eyes, runny nose, nausea, sweating, muscle aches). To help prevent withdrawal reactions, your doctor may direct you to take another medication. Withdrawal is more likely if you have used buprenorphine for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.

Do not remove the buprenorphine implants by yourself. This may cause severe withdrawal symptoms.

How do I store Buprenorphine?

Buprenorphine is best stored at 20° to 25°C. Protect from prolonged exposure to light. Retain in carton until time of use. Do not freeze.

There may be different brands of Buprenorphine that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.

You should not flush Buprenorphine down the toilet or pour them into a drain unless instructed to do so. It is important to properly discard this product when it is expired or no longer needed. Consult your pharmacist for more details about how to safely discard your product.

Precautions & warnings

What should I know before using Buprenorphine?

Before using buprenorphine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), liver disease, mental/mood disorders (such as confusion, depression), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged prostate), skin problems (such as scleroderma, skin infections, excessive scarring).

This drug may make you dizzy or drowsy. Alcohol or marijuana can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana. Alcohol also increases your risk for breathing problems.

Buprenorphine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using buprenorphine, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/”water pills”) or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using buprenorphine safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially confusion, dizziness, drowsiness, slow/shallow breathing, and QT prolongation (see above).

Before using this medication, women of childbearing age should talk with their doctor(s) about the benefits and risks. Tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, use this medication for the shortest possible time. Tell the doctor right away if you notice any symptoms in your newborn baby such as slow/shallow breathing, irritability, abnormal/constant crying, vomiting, or diarrhea.

This drug passes into breast milk and may rarely have undesirable effects on a nursing infant. Tell the doctor right away if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breast-feeding.

Is it safe during pregnancy or breast-feeding?

There are no adequate studies in women for determining risk when using this Buprenorphine during pregnancy or while breastfeeding. Please always consult with your doctor to weigh the potential benefits and risks before taking Buprenorphine. Buprenorphine is pregnancy risk category N according to the US Food and Drug Administration (FDA).

FDA pregnancy risk category reference below:

  • A=No risk,
  • B=No risk in some studies,
  • C=There may be some risk,
  • D=Positive evidence of risk,
  • X=Contraindicated,
  • N=Unknown

Side effects

What side effects can occur from Buprenorphine?

Drowsiness, dizziness, lightheadedness, constipation, or headache may occur. Itching, pain, or redness at the insertion/removal site may also occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

To prevent constipation, eat a diet adequate in fiber, drink plenty of water, and exercise. Consult your pharmacist for help in selecting a laxative (such as a stimulant type with stool softener).

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Severe (possibly fatal) breathing problems can occur if this medication is abused, injected, or mixed with other depressants (such as alcohol, benzodiazepines including diazepam, other opioids).

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as agitation, confusion, hallucinations), stomach/abdominal pain, signs of your adrenal glands not working well (such as unusual tiredness, weight loss).

Get medical help right away if you have any very serious side effects, including: fainting, fast/irregular heartbeat, severe dizziness, slow/shallow breathing, unusual drowsiness/difficulty waking up.

Although this medication is used to prevent withdrawal reactions, it may rarely cause narcotic withdrawal symptoms, including diarrhea, severe mental/mood changes (such as anxiety, irritability, trouble sleeping), muscle stiffness or shakiness. This is more likely when you first start treatment or if you have been using long-acting opioids such as methadone. If such symptoms occur, tell your doctor right away.

This drug may rarely cause serious (possibly fatal) liver disease. Get medical help right away if you have any symptoms of liver damage, such as: nausea/vomiting that doesn’t stop, loss of appetite, severe stomach/abdominal pain, yellowing eyes/skin, dark urine.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Not everyone experiences these side effects. There may be some side effects not listed above. If you have any concerns about a side-effect, please consult your doctor or pharmacist.

Interactions

What drugs may interact with Buprenorphine?

Some products that may interact with this drug are: naltrexone, certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol).

Many drugs besides buprenorphine may affect the heart rhythm (QT prolongation), such as amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, among others.

The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is used with other products that may also affect breathing or cause drowsiness. Tell your doctor or pharmacist if you are taking other products such as alcohol, marijuana, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), and other narcotic pain relievers (such as codeine, hydrocodone).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Deaths have occurred when buprenorphine has been misused by injecting it (“shooting up”), especially when used in combination with benzodiazepines (such as diazepam) or other depressants such as alcohol or additional opioids.

Buprenorphine may interact with other drugs that you are currently taking, which can change how your drug works or increase your risk for serious side effects. To avoid any potential drug interactions, you should keep a list of all the drugs you are using (including prescription drugs, nonprescription drugs and herbal products) and share it with your doctor and pharmacist. For your safety, do not start, stop, or change the dosage of any drugs without your doctor’s approval.

Does food or alcohol interact with Buprenorphine?

Buprenorphine may interact with food or alcohol by altering the way the drug works or increase the risk for serious side effects. Please discuss with your doctor or pharmacist any potential food or alcohol interactions before using this drug.

What health conditions may interact with Buprenorphine?

Buprenorphine may interact with your health condition. This interaction may worsen your health condition or alter the way the drug works. It is important to always let your doctor and pharmacist know all the health conditions you currently have.

Dosage

The information provided is not a substitute for any medical advice. You should ALWAYS consult with your doctor or pharmacist before using this Buprenorphine.

What is the dose of Buprenorphine for an adult?

Usual Adult Dose for Opiate Dependence – Maintenance

MAINTENANCE: This drug should be used as part of a complete treatment plan to include counseling and psychosocial support.

SUBLINGUAL Tablets:

Following 2-day induction: Adjust dose in 2 to 4 mg increments/decrements to a level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms

-Target dose: 16 mg sublingually once a day; range 4 to 24 mg/day

-Maximum dose: 24 mg/day; higher doses have not shown a clinical advantage

Comment: Buprenorphine with naloxone is the preferred drug for maintenance treatment; unsupervised maintenance treatment with buprenorphine should be limited to those who cannot tolerate buprenorphine-naloxone.

EXTENDED-RELEASE SUBCUTANEOUS Injection (Sublocade[R]):

Following a minimum of 7-days of treatment with a transmucosal product delivering the equivalent of 8 to 24 mg buprenorphine per day:

-Initial dose: 300 mg subcutaneously once a month for 2 months

-Maintenance dose: 100 mg subcutaneously once a month

-Maintenance dose may be increased to 300 mg monthly for those tolerating lower dose and demonstrating a less than satisfactory clinical response, e.g. self-reported illicit opioid use or positive urine drug screens

Comments:

-Initiating therapy with subcutaneous injections has not been studied; subcutaneous injections should only be initiated following induction and dose-adjustment with a transmucosal buprenorphine-containing product.

-Monthly doses should allow for a minimum of 26 days between doses; occasional delays in dosing of up to 2 weeks are not expected to have a clinically significant impact on treatment effect.

SUBDERMAL IMPLANT (Probuphine[R]): For use in opioid-tolerant patients who meet ALL of the following criteria:

-Achieved and sustained prolonged clinical stability on transmucosal buprenorphine as evidenced by a stable dose for 3 months or longer without any need for supplemental dosing or dose adjustments.

-Currently receiving buprenorphine maintenance (with or without naloxone) at doses of 8 mg/day or less, or equivalent transmucosal product (e.g. Bunavail[R] buprenorphine 4.2 mg/naloxone 0.7 mg per day or less; or Zubsolv[R] buprenorphine 5.7 mg/naloxone 1.4 mg per day or less)

-Patients should not be tapered to a lower dose for the sole purpose of transitioning to the implant.

Insert 1 dose subdermally in the inner side of the upper arm

-Remove at the end of the sixth month

Comments:

-Implant insertions and removals should be performed by certified healthcare providers.

-Each dose consists of 4 implants; each implant contains 74.2 mg of buprenorphine

-After 1 insertion in each arm, most patients should be transitioned back to transmucosal products for continued treatment as there is no experience with inserting additional implants into other sites in the arm or into a previously-used site.

There is no maximum recommended duration for maintenance therapy as indefinite treatment may be required; when the decision is made to discontinue, doses should be tapered.

Usual Adult Dose for Pain

Initial dose: 0.3 mg deep IM or slow IV (over at least 2 minutes); may repeat this dose once after 30 to 60 minutes if needed; then, 0.3 mg IV/IM every 6 hours as needed

-A single 0.6 mg IM dose may be given to patients who are not in a high risk category (see Warnings)

Maximum single dose: 0.3 mg (IV) or 0.6 mg (IM)

Comments:

-Use extra caution with IV administration, especially the first dose.

-Monitor closely for respiratory depression, especially within the first 24 to 72 hours.

-Use the lowest effective dose for the shortest duration consistent with the individual patient’s treatment goals.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.

Usual Adult Dose for Chronic Pain

BUCCAL Film:

Opioid-Naive and Opioid Non-Tolerant:

As Initial Opioid Analgesic: 75 mcg buccally once a day, or if tolerated every 12 hours for at least 4 days; then increase to 150 mcg every 12 hours

-Titrate individually in increments of 150 mcg every 12 hours no more frequently than every 4 days to a dose that provides adequate analgesia and minimizes adverse reactions

Maximum dose: 900 mcg every 12 hours

-Doses of 600 mcg, 750 mcg, and 900 mcg should only be used following titration from lower doses

CONVERSION from Other Opioids to BUCCAL Film: To reduce the risk of opioid withdrawal, taper patients to no more than 30 mg/day oral morphine mg equivalents (MME) before beginning therapy

Discontinue all around-the-clock opioid drugs when initiating buccal film

For opioid dose of less than 30 MME/day prior to taper:

-Initial dose: 75 mcg buccally once a day, or every 12 hours

For opioid dose between 30 and 89 MME/day prior to taper:

-Initial dose: 150 mcg buccally every 12 hours

For opioid dose between 90 and 160 MME/day prior to taper:

-Initial dose: 300 mcg buccally every 12 hours

For opioid doses greater than 160 MME/day: Consider alternate analgesics as buccal film may not provide adequate analgesia

Conversion from Methadone: Close monitoring will be of particular importance as methadone has a long half-life and accumulates in the plasma; no specific conversion is provided with an understanding that there is wide interpatient variability.

TRANSDERMAL System:

Opioid-Naive and Opioid Non-Tolerant:

As Initial Opioid Analgesic: Apply 5 mcg/hr patch transdermally; change every 7 days

-Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; minimal titration interval is 72 hours

Maximum dose: 20 mcg/hr

-Transdermal patches of 7.5, 10, 15, and 20 mcg/hour are only for use in patients who are opioid-tolerant

CONVERSION from Other Opioids to TRANSDERMAL System:

Discontinue all other around-the-clock opioid drugs when initiating therapy

-For prior opioid dose of less than 30 oral morphine mg equivalents (MME) per day: Initiate with 5 mcg/hr patch applied transdermally at next dosing interval

-For prior opioid dose between 30 and 80 MME/day: Taper around-the-clock opioids for up to 7 days to no more than 30 MME/day; then, initiate with 10 mcg/hr patch applied transdermally at next dosing interval; may use short-acting analgesics as needed until analgesic efficacy is attained

-For prior opioid dose greater than 80 MME/day: Consider an alternate analgesic as transdermal therapy may not provide adequate analgesia

Conversion from Methadone: Close monitoring will be of particular importance as methadone has a long half-life and accumulates in the plasma; no specific conversion is provided with an understanding that there is wide interpatient variability.

Comments:

-The buccal film and transdermal system should be prescribed by healthcare providers knowledgeable in the use of potent opioids for chronic pain; these products are not for use as as-needed analgesics.

-Monitor patients closely for respiratory depression, especially within 24 to 72 hours after initiating therapy and with dose increases.

-If pain level increases after dose stabilization, attempt to identify source of increased pain before increasing dose; rescue medication with an immediate-release analgesic may be needed.

-Because of the risks of opioid addiction, abuse, and misuse, this drug should be reserved for patients for whom alternative treatment options have not or are not expected to be tolerated; or have not or are not expected to provide adequate analgesia.

-Upon discontinuation, use a gradual downward titration; for patients on transdermal system, may need to switch to an immediate-release opioid.

Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.

Usual Adult Dose for Opiate Dependence – Induction

Treatment should be initiated when objective and clear signs of moderate opioid withdrawal appear, and

-at least 4 hours have elapsed since last use of heroin or other short-acting opioids

-at least 24 hours have elapsed since last use of methadone or other long-acting opioids

INDUCTION:

Day 1: 8 mg sublingually once a day (may give in 2 to 4 mg increments, if preferred)

Day 2: 16 mg sublingually once a day

Comments:

-This drug should be used as part of a complete treatment plan to include counseling and psychosocial support.

-Buprenorphine (without naloxone) is the preferred drug for induction.

-Adequate treatment doses should be given as soon as possible as gradual induction over several days has led to higher dropout rates

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

Transdermal:

-Severe hepatic impairment: Consider analgesics that permit more flexibility in dosing

Buccal Film:

-Severe hepatic impairment: Reduce starting dose and titration dose by one-half (i.e. from 150 mcg to 75 mcg)

Sublingual Tablets:

-Mild hepatic impairment: No adjustment recommended

-Moderate hepatic impairment: Use with caution and close monitoring

-Severe hepatic impairment: Consider reducing the starting and titration dose by one-half; monitor closely for signs and symptoms of toxicity

Extended-release subcutaneous injection:

-Moderate to severe hepatic impairment: Not recommended

-For patients developing moderate to severe hepatic impairment while on treatment, monitor for signs and symptoms of toxicity or overdose for several months.

Implant:

-Moderate to severe hepatic impairment: Not recommended

-For patients developing moderate to severe hepatic impairment while on treatment, monitor for signs and symptoms of toxicity or overdose, if signs and symptoms of toxicity or overdose are observed, the implant should be removed.

Dose Adjustments

Elderly: Initiate therapy at the low end of the dosing range and titrate slowly to account for increased sensitivity to drug

Oral Mucositis (buccal film): Reduce starting dose and dose titration by one-half in patients with known or suspected oral mucositis

Parenteral:

-Reduce dose by one-half in patients at high risk for respiratory depression, including, but not limited to patients with respiratory diseases, patients in the immediate postoperative period, the elderly, debilitated patients, and those concomitantly receiving CNS depressants.

CYP450 Inhibitors or Inducers:

-Monitor patients starting or stopping CYP450 3A4 inhibitors or inducers for potential over or under dosing

Unstable Patients undergoing Treatment for Opioid Dependence:

-Some patients may need more intensive behavioral treatment environment; decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.

DISCONTINUATION:

-Abrupt discontinuation is not recommended; when therapy is ending, taper gradually while monitoring for signs and symptoms of withdrawal; if signs and symptoms of withdrawal develop, raise dose to previous level and taper more slowly.

-Patients undergoing treatment for opioid dependence should be advised of the potential to relapse.

-Patients receiving extended-release subcutaneous injection should be monitored for several months following discontinuation for signs and symptoms of withdrawal due to characteristics of the formulation; after steady-state has been achieved (4 to 6 months), detectable levels of buprenorphine may be present for 12 months or longer.

What is the dose of Buprenorphine for a child?

Usual Pediatric Dose for Pain

2 to 12 years:

Initial dose: 2 to 6 mcg/kg IM or slow IV every 4 to 6 hours

-Some patients may not need to be remedicated for 6 to 8 hours; fixed interval or round the clock dosing should not be used until the proper inter-dose interval has been established

Over 12 years:

Initial dose: 0.3 mg deep IM or slow IV (over at least 2 minutes); may repeat this dose once after 30 to 60 minutes if needed; then, 0.3 mg IV/IM every 6 hours as needed

Maximum single dose: 0.3 mg

Comments:

-Use extra caution with IV administration, especially the first dose.

-Monitor closely for respiratory depression, especially within the first 24 to 72 hours.

-Use the lowest effective dose for the shortest duration consistent with the individual patient’s treatment goals.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.

Usual Pediatric Dose for Opiate Dependence – Maintenance

16 years or older:

MAINTENANCE: This drug should be used as part of a complete treatment plan to include counseling and psychosocial support.

SUBLINGUAL Tablets:

Following 2-day induction: Adjust dose in 2 to 4 mg increments/decrements to a level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms

-Target dose: 16 mg sublingually once a day; range 4 to 24 mg/day

-Maximum dose: 24 mg/day; higher doses have not shown a clinical advantage

Comment: Buprenorphine with naloxone is the preferred drug for maintenance treatment; unsupervised maintenance treatment with buprenorphine should be limited to those who cannot tolerate buprenorphine-naloxone.

SUBDERMAL IMPLANT (Probuphine[R]): For use in opioid-tolerant patients who meet ALL of the following criteria:

-Achieved and sustained prolonged clinical stability on transmucosal buprenorphine as evidenced by a stable dose for 3 months or longer without any need for supplemental dosing or dose adjustments.

-Currently receiving buprenorphine maintenance (with or without naloxone) at doses of 8 mg/day or less, or equivalent transmucosal product (e.g. Bunavail[R] buprenorphine 4.2 mg/naloxone 0.7 mg per day or less; or Zubsolv[R] buprenorphine 5.7 mg/naloxone 1.4 mg per day or less)

-Patients should not be tapered to a lower dose for the sole purpose of transitioning to the implant.

Insert 1 dose subdermally in the inner side of the upper arm

-Remove at the end of the sixth month

Comments:

-Implant insertions and removals should be performed by certified healthcare providers.

-Each dose consists of 4 implants; each implant contains 74.2 mg of buprenorphine

-After 1 insertion in each arm, most patients should be transitioned back to transmucosal products for continued treatment as there is no experience with inserting additional implants into other sites in the arm or into a previously-used site.

There is no maximum recommended duration for maintenance therapy as indefinite treatment may be required; when the decision is made to discontinue, doses should be tapered.

Usual Pediatric Dose for Opiate Dependence – Induction

16 years or older:

Treatment should be initiated when objective and clear signs of moderate opioid withdrawal appear, and

-at least 4 hours have elapsed since last use of heroin or other short-acting opioids

-at least 24 hours have elapsed since last use of methadone or other long-acting opioids

INDUCTION:

Day 1: 8 mg sublingually once a day (may give in 2 to 4 mg increments, if preferred)

Day 2: 16 mg sublingually once a day

Comments:

-This drug should be used as part of a complete treatment plan to include counseling and psychosocial support.

-Buprenorphine (without naloxone) is the preferred drug for induction.

-Adequate treatment doses should be given as soon as possible as gradual induction over several days has led to higher dropout rates.

Precautions

Safety and efficacy of the IM/IV parenteral product have not been established in patients younger than 2 years.

Safety and efficacy of sublingual tablets or implant for subdermal administration have not been established in patients younger than 16 years.

Safety and efficacy of buccal film, transdermal patch, or extended-release subcutaneous injection have not been established in patients younger than 18 years.

How is Buprenorphine available?

Buprenorphine is available in the following dosage forms and strengths:

  • Injectable solution,
  • Sublingual tablet,
  • Transdermal film, extended release,
  • Subcutaneous solution, extended release,
  • Compounding powder,
  • Subcutaneous implant,
  • Buccal film.

What should I do in case of an emergency or overdose?

In case of an emergency or an overdose, call your local emergency services or go to your nearest emergency room.

What should I do if I miss a dose?

If you miss a dose of Buprenorphine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your regular dose as scheduled. Do not take a double dose.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Review Date: August 29, 2018 | Last Modified: August 29, 2018

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