Buprenorphine Hydrochloride

FDA Drug Information • Also known as: Belbuca, Buprenorphine Hydrochloride

Brand Names: Belbuca, Buprenorphine Hydrochloride
Dosage Form: POWDER
Product Type: BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUPRENORPHINE HYDROCLORIDE INJECTION Addiction, Abuse, and Misuse Because the use of Buprenorphine HCl 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 and reassess all patients regularly for the development of these behaviors and conditions (see WARNINGS ). Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of buprenorphine HCl, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression proper dosing and titration of buprenorphine HCl are essential (see WARNINGS ) . Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death Reserve concomitant prescribing of buprenorphine HCl and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. (see WARNINGS , PRECAUTIONS ). Neonatal Opioid Withdrawal Syndrome If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery (see WARNINGS ).

Description

DESCRIPTION Buprenorphine Hydrochloride Injection is a partial opioid agonist. The chemical name of buprenorphine hydrochloride is 21-(Cyclopropyl-7α-[( S )-1-hydroxy-1,2,2- trimethylpropyl]-6,14- endo -ethano-6,7,8,14-tetrahydrooripavine hydrochloride. Buprenorphine hydrochloride is a white powder, weakly acidic and with limited solubility in water. Buprenorphine HCl Injection is a clear, sterile, injectable agonist-antagonist analgesic intended for intravenous or intramuscular administration. Each mL of Buprenorphine HCl Injection contains 0.324 mg buprenorphine hydrochloride (equivalent to 0.3 mg buprenorphine), 50 mg anhydrous dextrose, water for injection and HCl to adjust pH. Buprenorphine hydrochloride has the molecular formula, C 29 H 41 NO 4 HCl, and the following structure: Molecular weight: 504.10 chemical structure

What Is Buprenorphine Hydrochloride Used For?

INDICATIONS AND USAGE Buprenorphine HCl Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see WARNINGS: Addiction, Abuse, and Misuse ] reserve Buprenorphine HCl Injection for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia. Buprenorphine HCl Injection should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Dosage and Administration

DOSAGE AND ADMINISTRATION Buprenorphine HCl should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration consistent with individual patients treatment goals [see WARNINGS ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Buprenorphine HCl for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Buprenorphine HCl. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ] . Inspect Buprenorphine HCl for particulate matter and discoloration prior to administration. Dosing Adults and Pediatric Patients over 12 years of Age The initial starting dose is 1 mL buprenorphine HCl (0.3 mg buprenorphine) given by deep intramuscular or slow (over at least 2 minutes) intravenous injection at up to 6-hour intervals, as needed. Repeat once (up to 0.3 mg) if required, 30 to 60 minutes after initial dosage, giving consideration to previous dose pharmacokinetics, and thereafter only as needed. In high-risk patients (e.g., elderly, debilitated, presence of respiratory disease, etc.) and/or in patients where other CNS depressants are present, such as in the immediate postoperative period, the dose should be limited to the minimum required. Extra caution should be exercised with the intravenous route of administration, particularly with the initial dose. Occasionally, it may be necessary to administer single doses of up to 0.6 mg to adults depending on the severity of the pain and the response of the patient. This dose should only be given I.M. and only to adult patients who are not in a high-risk category [see WARNINGS and PRECAUTIONS ] . At this time, there are insufficient data to recommend single doses greater than 0.6 mg for long-term use. Pediatric Patients Buprenorphine HCl has been used in pediatric patients 2 to 12 years of age at doses between 2 to 6 micrograms/kg of body weight given every 4 to 6 hours. There is insufficient...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS The most frequent side effect in clinical studies involving 1,133 patients was sedation which occurred in approximately two-thirds of the patients. Although sedated, these patients could easily be aroused to an alert state. Other less frequent adverse reactions occurring in 5 to 10% of the patients were: Nausea Dizziness/Vertigo Occurring in 1 to 5% of the patients: Sweating Headache Hypotension Nausea/Vomiting Vomiting Hypoventilation Miosis The following adverse reactions were reported to have occurred in less than 1% of the patients: CNS Effect: confusion, blurred vision, euphoria, weakness/fatigue, dry mouth, nervousness, depression, slurred speech, paresthesia. Cardiovascular: hypertension, tachycardia, bradycardia. Gastrointestinal: constipation. Respiratory: dyspnea, cyanosis. Dermatological: pruritus. Ophthalmological: diplopia, visual abnormalities. Miscellaneous: injection site reaction, urinary retention, dreaming, flushing/warmth, chills/cold, tinnitus, conjunctivitis, Wenckebach block, and psychosis. Other effects observed infrequently include malaise, hallucinations, depersonalization, coma, dyspepsia, flatulence, apnea, rash, amblyopia, tremor, and pallor. The following reactions have been reported to occur rarely: loss of appetite, dysphoria/agitation, diarrhea, urticaria, and convulsions/lack of muscle coordination. Allergic Reactions: Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the postmarketing experience of buprenorphine HCl injection and other buprenorphine-containing products. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to buprenorphine HCl injection. In the United Kingdom, buprenorphine HCl was made available under monitored release regulation during the first year of sale, and yielded data from 1,736 physicians on 9,123 patients (17,120 administrations). Data on 240 children under the age of 18 years were included in this monitored release program. No important new adverse effects attributable to buprenorphine HCl were observed. Postmarketing Experience 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. Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY: Pharmacodynamics ] . Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ] . Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

Warnings and Precautions

WARNINGS Addiction, Abuse, and Misuse Buprenorphine HCl contains buprenorphine, a Schedule III controlled substance. As an opioid, buprenorphine HCl exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed buprenorphine HCl. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing buprenorphine HCl, and reassess all patients receiving buprenorphine HCl for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of buprenorphine HCl for the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as buprenorphine HCl, but use in such patients necessitates intensive counseling about the risks and proper use of buprenorphine HCl along with the frequent reevaluation for signs of addiction, abuse, and misuse. Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing buprenorphine HCl. Strategies to reduce these risks include proper product storage and control practices for a C-III drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory depression and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of buprenorphine HCl, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of buprenorphine HCl are essential. Overestimating the buprenorphine HCl dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for...

Contraindications

CONTRAINDICATIONS Buprenorphine HCl Injection is contraindicated in patients with: Significant respiratory depression [See WARNINGS ] . Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [See WARNINGS ]. Known or suspected gastrointestinal obstruction, including paralytic ileus [See WARNINGS ] . Hypersensitivity to buprenorphine (e.g. anaphylaxis) or any other ingredient in Buprenorphine HCl Injection [See WARNINGS ].

Overdosage

OVERDOSAGE Clinical Presentation Acute overdose with buprenorphine HCl can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Treatment of Overdose In the case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to buprenorphine overdose, administer an opioid antagonist. The healthcare provider must remember that buprenorphine is a long-acting depressant (36 to 48 hours), whereas the antagonists act for much shorter periods (one to three hours). Because the duration of opioid reversal is expected to be less than the duration of action of buprenorphine in buprenorphine HCl injection, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information. In an individual physically dependent on opioids, the administration of the usual dose of an opioid antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to...

How Supplied

HOW SUPPLIED Buprenorphine Hydrochloride Injection is supplied in amber glass vials of 1 mL (0.3 mg buprenorphine). NDC 0143-9246-05 ; carton of 5 vials. Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F). [USP Controlled Room Temperature]. Protect from prolonged exposure to light. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For Product Inquiry call 1-877-845-0689. Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised April 2024 PIN444-WES/5

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.