Buprenorphine + Naloxone

Sublingual
Opioid dependence

Severe: Contraindicated.

May be taken with or without food. Place under the tongue & allow to dissolve completely.

Severe resp insufficiency, acute alcoholism or delirium tremens. Severe hepatic impairment. Concomitant admin w/ opioid antagonists (naltrexone, nalmefene).

Patient w/ head injury, intracranial lesions, other circumstances where cerebrospinal pressure may be increased, history of seizure; hypotension, prostatic hypertrophy, urethral stenosis; myxoedema, hypothyroidism, adrenal cortical insufficiency (e.g. Addison's disease); biliary tract dysfunction. Severe renal and moderate hepatic impairment. Debilitated patients. Pregnancy and lactation.

Influenza, infection, pharyngitis, rhinitis, depression, anxiety, nervousness, abnormal thinking, decreased libido, migraine, hypertonia, dizziness, paraesthesia, somnolence, amblyopia, lacrimal disorder, HTN, vasodilatation, cough, diarrhoea, abdominal pain, vomiting, flatulence, dyspepsia, pruritus, urticaria, rash, back pain, arthralgia, myalgia, muscle spasms, urine abnormality, erectile dysfunction, chest pain, asthenia, pyrexia, chills, malaise, pain, peripheral oedema, abnormal LFT, decreased wt, injury.

PO: C

This drug may cause drowsiness, dizziness or impaired thinking, if affected, do not drive or operate machinery.

Monitor LFTs prior to and periodically during treatment; resp and mental status, CNS depression, symptoms of withdrawal, signs of addiction.

Symptoms: Resp depression, amblyopia, miosis, somnolence, hypotension, nausea, vomiting, and speech disorders. Management: Supportive and symptomatic treatment. Assure a patent airway and assisted or controlled ventilation.

Concomitant admin w/ benzodiazepines may result to death due to resp depression. May increase CNS depression w/ other CNS depressants and other opioid derivatives (e.g. methadone, antitussives, analgesics), barbiturates, clonidine, neuroleptics, anxiolytics other than benzodiazepines, sedative H₁-receptor antagonists, certain antidepressants. May reduce plasma levels w/ CYP3A4 inducers (e.g. phenobarbital, carbamazepine). May exaggerate effects w/ MAOIs.
Potentially Fatal: Blocked pharmacological effects w/ opioid antagonists (naltrexone, nalmefene).

May enhance sedative effect w/ alcohol.

Description:
Mechanism of Action: Buprenorphine is a partial agonist/antagonist at the µ- and kappa-opioid receptor of the brain. Its activity is attributed to its slowly reversible properties w/ the µ-opioid receptors which, over a prolonged period may minimise the need of addicted patients for drugs. Naloxone, a potent antagonist at the µ-opioid receptors, produces marked opioid antagonist effects and opioid withdrawal, thus deterring IV abuse.
Pharmacokinetics:
Absorption: Buprenorphine: Absorbed through the buccal mucosa. Time to peak plasma concentration: 90 min. Naloxone: Absorbed from the GI tract.
Distribution: Buprenorphine: It crosses the placenta, enters breast milk (small amounts). Plasma protein binding: Approx 96%. Naloxone: Extensively distributed into body tissues and fluids, particularly the brain; crosses the placenta. Plasma protein binding: Approx 32-45%.
Metabolism: Buprenorphine: Hepatically metabolised via oxidation by CYP3A4 isoenzyme to active metabolite N-dealkylbuprenorphine (norbuprenorphine), and via conjugation to glucuronide metabolites. Naloxone: Hepatically metabolised via glucuronide conjugation, w/ naloxone-3-glucuronide as major metabolite.
Excretion: Buprenorphine: Mainly via faeces (as unchanged drug); urine (as metabolites). Elimination half-life: 20 to >36 hr. Naloxone: Via urine (as metabolites).

Source: National Center for Biotechnology Information. PubChem Database. Buprenorphine, CID=644073, https://pubchem.ncbi.nlm.nih.gov/compound/Buprenorphine (accessed on Jan. 22, 2020)

Source: National Center for Biotechnology Information. PubChem Database. Naloxone, CID=5284596, https://pubchem.ncbi.nlm.nih.gov/compound/Naloxone (accessed on Jan. 22, 2020)

Store between 20-25°C.

Analgesics (Opioid)

N07BC51 - buprenorphine, combinations ; Belongs to the class of drugs used in the management of opioid dependence.

Anon. Buprenorphine and Naloxone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/03/2016.

Buckingham R (ed). Buprenorphine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2016.

Buckingham R (ed). Naloxone Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2016.

Buprenorphine Hydrochloride and Naloxone Hydrochloride Dehydrate Tablet (Actavis Pharma, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 07/03/2016.

Joint Formulary Committee. Buprenorphine with Naloxone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/03/2016.