Drug Facts
Composition & Profile
Identifiers & Packaging
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; VIAL LABEL Buprenorphine HCl Injection 0.3 mg (base)/mL Container Label NDC 0143- 9246 -01 Rx only Buprenorphine HCl Injection 0.3 mg (base)/mL FOR IM or IV USE 1 mL vial Protect from light Buprenorphine HCl Injection 0.3 mg (base)/mL Container Label; CARTON NDC 0143- 9246 -05 Rx only 5 x 1 mL vials Buprenorphine HCl Injection 0.3 mg/mL* FOR INTRAMUSCULAR OR INTRAVENOUS USE carton
- 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
- VIAL LABEL Buprenorphine HCl Injection 0.3 mg (base)/mL Container Label NDC 0143- 9246 -01 Rx only Buprenorphine HCl Injection 0.3 mg (base)/mL FOR IM or IV USE 1 mL vial Protect from light Buprenorphine HCl Injection 0.3 mg (base)/mL Container Label
- CARTON NDC 0143- 9246 -05 Rx only 5 x 1 mL vials Buprenorphine HCl Injection 0.3 mg/mL* FOR INTRAMUSCULAR OR INTRAVENOUS USE carton
Overview
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
Indications & 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 & 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 experience to recommend a dose in infants below the age of two years, single doses greater than 6 micrograms/kg of body weight, or the use of a repeat or second dose at 30 to 60 minutes (such as is used in adults). Since there is some evidence that not all pediatric patients clear buprenorphine faster than adults, fixed interval or “round-the-clock” dosing should not be undertaken until the proper inter-dose interval has been established by clinical observation of the child. Healthcare providers should recognize that, as with adults, some pediatric patients may not need to be remedicated for 6 to 8 hours. Safety and Handling Buprenorphine HCl is supplied in sealed vials and poses no known environmental risk to health care providers. Accidental dermal exposure should be treated by removal of any contaminated clothing and rinsing the affected area with water. Buprenorphine HCl is a potent opioid, and like all drugs of this class has been associated with abuse and dependence among healthcare providers. To control the risk of diversion, it is recommended that measures appropriate to the health care setting be taken to provide rigid accounting, control of wastage, and restriction of access. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Warnings & 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 opioid taper [see Dosage and Administration ] . Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of buprenorphine HCl with benzodiazepines or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Monitor patients closely for signs and symptoms of respiratory depression and sedation. Neonatal Opioid Withdrawal Syndrome Use of buprenorphine HCl for an extended period of time during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a extended period of time of the risk of neonatal opioid withdrawal syndrome and ensure that management by neonatology experts will be available at delivery [see WARNINGS , PRECAUTIONS: Information for Patients , Pregnancy ]. Opioid-Induced Hyperalgesia and Allodynia Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This condition differs from tolerance, which is the need for increasing doses of opioids to maintain a defined effect [see DEPENDENCE ]. Symptoms of OIH include (but may not be limited to) increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Cases of OIH have been reported, both with short-term and longer-term use of opioid analgesics. Though the mechanism of OIH is not fully understood, multiple biochemical pathways have been implicated. Medical literature suggests a strong biologic plausibility between opioid analgesics and OIH and allodynia. If a patient is suspected to be experiencing OIH, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching the patient to a different opioid moiety) [see DOSAGE and ADMINISTRATION , WARNINGS ]. Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of buprenorphine HCl in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. Patients with Chronic Pulmonary Disease : Buprenorphine HCl-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages of buprenorphine HCl [see WARNINGS ] . Elderly, Cachectic, or Debilitated Patients : Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating buprenorphine HCl and when buprenorphine HCl is given concomitantly with other drugs that depress respiration [see WARNINGS ]. Alternatively, consider the use of non-opioid analgesics in these patients. Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the 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. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. Severe Hypotension Buprenorphine HCl may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume, or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of buprenorphine HCl. In patients with circulatory shock, buprenorphine HCl may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of buprenorphine HCl in patients with circulatory shock. Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), buprenorphine HCl may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with buprenorphine HCl. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of buprenorphine HCl in patients with impaired consciousness or coma. QTc Prolongation Thorough QT studies with buprenorphine products have demonstrated QT prolongation ≤ 15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors. The risk of combining buprenorphine with other QT-prolonging agents is not known. Consider these observations in clinical decisions when prescribing Buprenorphine HCl to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia. Anaphylactic/Allergic Reactions Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. Buprenorphine HCl is contraindicated in patients with a history of hypersensitivity to buprenorphine. Risks of Use in Patients with Gastrointestinal Conditions Buprenorphine HCl is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The buprenorphine in buprenorphine HCl injection may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Increased Risk of Seizures in Patients with Seizure Disorders The buprenorphine in buprenorphine HCl injection may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during buprenorphine HCl therapy. Risks Driving and Operating Machinery Buprenorphine HCl may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of buprenorphine HCl and know how they will react to the medication [see PRECAUTIONS: Information for Patients ].
Boxed 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 ).
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 ].
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).
Similar Drugs
Related medications based on brand, generic name, substance, active ingredients.