BUPRENORPHINE

brands

Class

• Mu opioid receptor partial agonist

BUPRENORPHINE commonly prescribed for

(Bold for FDA approved)

How BUPRENORPHINE works

• Binds with strong affinity to the mu opioid receptor, preventing exogenous opioids from binding there and thus preventing the pleasurable effects of opioid consumption

• Because buprenorphine is a partial agonist, it can cause immediate withdrawal in a patient currently taking opioids (i.e., reduces receptor stimulation in the presence of a full agonist) but can relieve withdrawal if a patient is already experiencing it (i.e., increases receptor stimulation in the absence of a full agonist)

• Buprenorphine is also an antagonist at the kappa opioid receptor

• In combination with naloxone: naloxone is a mu opioid receptor antagonist and can therefore block the effects of buprenorphine; however, because naloxone has poor sublingual bioavailability, it does not interfere with buprenorphine’s effects when used properly. Naloxone does have good parenteral bioavailability; thus, if one tries to administer the buprenorphine/ naloxone formulation intravenously, naloxone will prevent any rewarding effects from buprenorphine.

How long until BUPRENORPHINE works

• Effects on withdrawal can be immediate

• Effects on reducing opioid use disorder/ dependence can take many months of treatment

Notable Side Effects

• Headache, constipation, nausea

• Oral hypoesthesia, glossodynia

• Orthostatic hypotension

Life Threatening Side Effects

• Respiratory depression

• Hepatotoxicity

weight gain

unusual

sedation

common

What to do about BUPRENORPHINE side effects

• Wait

• Reduce dose

• Switch to another agent

usual dosage range

• Sublingual: 8–32 mg/day

• Sublocade injection: maintenance dose is 100–300 mg monthly

• Brixadi injection, weekly: maintenance dose is 24–32 mg weekly

• Brixadi injection, monthly: maintenance dose is 64–128 mg monthly

Dosage Forms

• Sublingual tablet 2 mg, 8 mg

• Sublingual tablet (with naloxone) 2 mg/0.5 mg, 8 mg/2 mg

• Zubsolv sublingual tablet (with naloxone) 0.7 mg/0.18 mg, 1.4 mg/0.36 mg, 2.9 mg/0.71 mg, 5.7 mg/1.4 mg, 8.6 mg/2.1 mg, 11.4 mg/2.9 mg

• Sublingual film (with naloxone) 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, 12 mg/3 mg

• Sublocade monthly injection 100 mg/0.5 mL, 300 mg/1.5 mL

• Brixadi weekly injection 8 mg/0.16 mL, 16 mg/0.32 mL, 24 mg/0.48 mL, 32 mg/0.64 mL

• Brixadi monthly injection 64 mg/0.18 mL, 96 mg/0.27 mL, 128 mg/0.36 mL

long term use

• Maintenance treatment may be required; typical maintenance period is up to 2 years but may need to be indefinite

habit forming

• Buprenorphine is a Schedule III drug

• Can cause physical dependence

Renal Impairment

• Dose adjustment not necessary

Hepatic Impairment

• In patients with moderate to severe impairment, plasma levels of buprenorphine can be higher and half-life can be longer; thus, these patients should be monitored for signs and symptoms of toxicity or overdose

• For severe impairment, the dose should be reduced

• Hepatic impairment results in reduced clearance of naloxone, so patients with severe impairment should not take buprenorphine/naloxone combinations; caution is warranted for patients with moderate impairment

Cardiac Impairment

• Use with caution

Elderly

• Use with caution

• Some patients may tolerate lower doses better

• Monitor patients for sedation or respiratory depression

Children and Adolescents

• Safety and efficacy have not been established

Pregnancy

• Controlled studies have not been conducted in pregnant women

• Buprenorphine may be preferable to methadone in pregnant women

• Neonatal opioid withdrawal syndrome has been reported following use of buprenorphine during pregnancy

• In animal studies, adverse events have been observed at clinically relevant doses; no clear teratogenic effects were seen, but increases in skeletal abnormalities were observed in rats and rabbits given daily buprenorphine at doses 5.4 and 10.8 times the maximum human recommended dose

• Not generally recommended for use during pregnancy, especially during first trimester

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed