buprenorphine hydrochloride

Administer Buprenorphine Sublingual Tablets sublingually as a single daily dose. ( 2.1 ) • Strongly consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) at the time Buprenorphine Sublingual Tablets are initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose. ( 2.2 ) • To avoid precipitating withdrawal, induction with Buprenorphine Sublingual Tablets should be undertaken when objective and clear signs of withdrawal are evident. ( 2.3 ) • Buprenorphine and naloxone sublingual film or buprenorphine and naloxone sublingual tablets are generally initiated after two days of Buprenorphine Sublingual Tablet titration. ( 2.4 ) • Administer Buprenorphine Sublingual Tablets as directed in the Full Prescribing Information. ( 2.3 , 2.4 , 2.5 ) • Buprenorphine Sublingual Tablets must be administered whole. Do not cut, chew, or swallow Buprenorphine Sublingual Tablets. ( 2.5 ) • When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal. ( 2.9 ) 2.1 Important Dosage and Administration Instructions Buprenorphine Sublingual Tablets are administered sublingually as a single daily dose. Buprenorphine Sublingual Tablets do not contain naloxone and is preferred for use only during induction. Following induction, buprenorphine and…

The following serious adverse reactions are described elsewhere in the labeling: • Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] • Respiratory and CNS Depression [see Warnings and Precautions ( 5.2 , 5.3 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.6 )] • Opioid Withdrawal [see Warnings and Precautions ( 5.7 , 5.10 )] • Hepatitis, Hepatic Events [see Warnings and Precautions ( 5.8 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] • Orthostatic Hypotension [see Warnings and Precautions ( 5.16 )] • Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions ( 5.17 )] • Elevation of Intracholedochal Pressure [see Warnings and Precautions ( 5.18 )] Adverse events commonly observed with administration of buprenorphine are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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…

Buprenorphine Sublingual Tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions ( 5.9 )] . Hypersensitivity to buprenorphine. ( 4 )

Clinical Presentation: The manifestations of acute overdose include pinpoint pupils, sedation, hypotension, hypoglycemia, respiratory depression, and death. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose: In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully. When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluids, vasopressors, and other supportive measures should be employed as indicated. In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. An opioid overdose reversal agent may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary. The long duration of action of Buprenorphine Sublingual Tablets should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose. Insufficient duration of monitoring may put patients at risk.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Table 3 includes clinically significant drug interactions with Buprenorphine Sublingual Tablets. Table 3. Clinically Significant Drug Interactions with Buprenorphine Sublingual Tablets 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 ( 5.2 , 5.3 )] . If concomitant use is warranted, strongly consider recommending or prescribing an opioid overdose reversal agent, as is recommended for all patients on buprenorphine treatment for opioid use disorder [see Warnings and Precautions ( 5.2 )]. Examples: Benzodiazepines and other sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. 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 Buprenorphine Sublingual Tablets is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology ( 12.3 )], 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 Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets 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 ( 12.3 )], 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 ( 12.3 )], 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 Buprenorphine Sublingual Tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets and atazanavir with and without ritonavir, and reduce dose of Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets 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 Buprenorphine Sublingual Tablets for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Buprenorphine Sublingual Tablets 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 recommending or prescribing an opioid overdose reversal agent, as is recommended for all patients on buprenorphine treatment for opioid use disorder [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 , 5.3 )]. Examples: cyclobenzaprine, metaxalone. 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 Buprenorphine Sublingual Tablets are used concomitantly with anticholinergic drugs. • Benzodiazepines : Use caution in prescribing Buprenorphine Sublingual Tablets for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse. ( 7 ) • CYP3A4 Inhibitors and Inducers : Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over- or under- dosing. ( 7 ) • Antiretrovirals: Patients who are on chronic buprenorphine treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Monitor patients taking buprenorphine and atazanavir with and without ritonavir, and reduce dose of buprenorphine if warranted. ( 7 ) • Serotonergic Drugs : Concomitant use may result in serotonin syndrome. Discontinue Buprenorphine Sublingual Tablets if serotonin syndrome is suspected. ( 7 )