Drug information of Buprenorphine

Mechanism of effect

 Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at mu and delta opioid receptors in CNS and antagonistic effects at kappa opioid receptor.

Pharmacodynamic

Buprenorphine is a synthetic opioid analgesic and thebaine derivative, with a longer duration of action than morphine. Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues.

In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Buprenorphine may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur.

Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Pharmacological effects peaks at 15 minutes and persists for 6 hours or longer when given intramuscularly. When given intravenously, the time to onset and peak effect are shortened.

Pharmacokinetics

Bioavailability: 79%

Onset: IM, 15 min

Duration: 4-10 hr

Peak plasma time: <2 min

Peak plasma concentration: 18 ng/mL

Protein bound: 96%

Vd: 97-187 L/kg

Metabolism: Liver (N-dealkylation)

Metabolites: Norbuprenorphine (N-dealkylbuprenorphine)

Half-life: 2.2 hr

Excretion: Urine, feces

Drug indications

Pain

Dosage

Usual Adult Dose for Opiate Dependence

Treatment should be initiated when objective and clear signs of moderate opioid withdrawal appear AND not less than 4 hours after the patient has last used heroin or other short-acting opioids OR not less than 24 hours after 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

MAINTENANCE:

-Adjust 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

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.

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

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

Maximum dose: 900 mcg every 12 hours.

Transdermal System:

Opioid-Naive and Opioid Non-Tolerant:

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

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

Maximum dose: 20 mcg/hr

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

Usual Pediatric Dose for Opiate Dependence

Treatment should be initiated when objective and clear signs of moderate opioid withdrawal appear AND not less than 4 hours after the patient has last used heroin or other short-acting opioids OR not less than 24 hours after last use of methadone or other long-acting opioids:

16 years or older:

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 dal

MAINTENANCE:

-Adjust 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.

Drug contraindications

hypersensitivity to this drug

Side effects

depression , Anxiety , Insomnia , nausea , vomiting , Seizures , vertigo , hallucinations

Interactions

Pregabalin , Doxepin , Midazolam , Hydroxyzine , fentanyl , Amiodarone , Erythromycin , Ondansetron , Isoniazid , Buspirone , Paroxetine , Dofetilide , Phenelzine , Quinidine , isocarboxazid , methylene blue , Nefazodone , Tryptophan , Venlafaxine , Carbamazepine , Ketoconazole , escitalopram , Linezolid , lithium , Sotalol , Fluvoxamine , Fluoxetine , Phenobarbital , Phenytoin , Granisetron , Trazodone , Tranylcypromine , Duloxetine , Disopyramide , Rizatriptan , Sertraline , Sodium Oxybate , Prochlorperazine , Tapentadol , rasagiline , propoxyphene , Pentazocine , Amphetamine , Dolasetron , vandetanib , sparfloxacin , Butalbital and Acetaminophen , Promazine , Chloral hydrate , Halofantrine , Grepafloxacin , Molindone , Alvimopan , Perampanel , Paraldehyde , Butorphanol , Acetaminophen and benzhydrocodone , Tasimelteon , Ramelteon , Secobarbital , Tolcapone , Temazepam , Clorazepate , Quazepam , Cariprazine , Oxymorphone , Lorlatinib , Ethchlorvynol , bedaquiline , Blonanserin , lasmiditan , Nabilone , Rufinamide , stiripentol , ethotoin

Alerts

• Partial agonist at the mu opioid receptor and a schedule controlled opioid exposes users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids owing to the larger amount of active opioid present.
• Serious, life-threatening, or fatal respiratory depression reported; may occur more frequently in elderly or debilitated patients, or in conditions associated with hypoxia or hypercapnia (even moderate therapeutic doses).
• Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy.
• Accidental exposure reported, including fatalities.
• Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension.
• Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients.
• QTc prolongation observed in healthy individuals at 40 mcg/hr; avoid in patients with history of long QT syndrome or coadministration with class IA (eg, quinidine, procainamide, disopyramide) or class III (eg, sotalol, amiodarone, dofetilide) antiarrhythmics.
• Respiratory depressant effects of opioids may include carbon dioxide retention and lead to elevated CSF pressure.
• Can cause severe hypotension; caution with depleted blood volume or coadministration of drugs that that affect vasomotor tone (eg, phenothiazines), vasodilators, or antihypertensives.
• Cases of cytolytic hepatitis and hepatitis with jaundice observed in individuals receiving buprenorphine SL for opioid dependence treatment; increased risk for overdose with moderate or severe hepatic impairment .
• Anaphylactic reactions reported.
• Caution in severe renal impairment.
• Severe hepatic impairment can cause increased buprenorphine plasma levels and prolonged half-life, but not in subjects with mild hepatic impairment; dose adjustment recommended in patients with moderate or severe hepatic; consider reducing the dose by half and closely monitor for signs and symptoms of toxicity and overdose.
• May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus.
• Similar to other opioids, may aggravate seizure disorders by lowering seizure threshold.
• Patients with cancer who have oral mucositis may absorb buprenorphine more rapidly than intended and have higher plasma levels of buprenorphine.
• Special risk groups may experience increased adverse reactions; caution with alcoholism, delirium tremens, adrenocortical insufficiency, CNS depression, debilitation, kyphoscoliosis associated with respiratory compromise, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, severe impairment of hepatic, pulmonary or renal function, and toxic psychosis.
• Prescribers should discuss with patients importance and benefits of management of opioid addiction throughout pregnancy.
• Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency.
• Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible.

Points of recommendation

To make sure this medicine is safe for you, tell your doctor if you have:

• If you have an allergy to buprenorphine or any other part of buprenorphine injection.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood; or stomach or bowel block or narrowing.
• If you have liver disease.
• If you or a family member have a long QT on ECG.
• If you are taking any of these drugs: Butorphanol, nalbuphine, or pentazocine.
• If you are using another drug that has the same drug in it.
• If you are taking any of these drugs: Certain drugs to treat a heartbeat that is not normal like amiodarone, disopyramide, dofetilide, procainamide, quinidine, or sotalol.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are taking any of these drugs: Linezolid or methylene blue.

 

• This medicine may cause withdrawal symptoms if you are dependent or addicted to narcotics. Talk with your doctor.
• Do not take buprenorphine injection with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
• Very bad and sometimes deadly liver problems have happened with this medicine. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Long-term use of an opioid drug like buprenorphine injection may lead to lower sex hormone levels. This may lead to signs like change in sex ability in men, no menstrual period in women, lowered interest in sex, or fertility problems. Call your doctor if you have any of these signs.
• This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking this medicine.
• If you are 65 or older, use buprenorphine injection with care. You could have more side effects.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.
• Tell your doctor if you are breast-feeding or plan to breast-feed. This medicine passes into breast milk and may harm your baby.

Related drugs

fentanyl , Methadone , Normethadone , Pethidine , Oxycodone , morphine , codeine , Tapentadol , Butorphanol