Buprenorphine/ Naloxone

Registered South African indications:

• Opioid dependance

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe hepatic impairment
• Severe respiratory insufficiency
• Acute alcoholism
• Delirium tremens
• Coadministration with opioid antagonists

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Respiratory insufficiency 
• Kyphoscoliosis
• Abrupt withdrawal
• Adolescents
• Hypotension
• Head injury
• Intracranial lesions
• History of seizures
• Prostatic hypertrophy
• Urethetric stenosis
• Hypothyroidism
• Myxoedema
• Adrenal cortical insufficiency
• Biliary tract dysfunction
• Debilitated patients
• Galactose intolerance

Forms avail. in SA and covered in this monograph: slt

Opioid dependance

Buprenorphine/ Naloxone
2/0.5 (mg)
8/2 (mg)

• Oral (slt): Initial: 1-2 tab (2/0.5mg), dly; 1-2 additional tab may be required on Day 1; Max: 3 tab (8/2mg)/24hrs

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To be taken when symptoms of withdrawal begin but not less than 6hrs after the last use of opioids or 24hrs after use of methadone

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If coadministered with methadone, the dose of methadone should be reduced to a max of 30mg, dly

Not established for use in children below 15 years

Pregnancy

• Caution; not recommended
• There are no adequate data from the use of Buprenorphine/Naloxone in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown
• Towards the end of pregnancy, buprenorphine may induce respiratory depression in the newborn infant even after a short period of administration. Long-term administration of buprenorphine during the last three months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed for several hours to several days after birth
• Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in neonates
• Furthermore, the use of buprenorphine/naloxone during pregnancy should be assessed by the physician. Buprenorphine/naloxone should be used during pregnancy only if the potential benefit outweighs the potential risk to the foetus

Breastfeeding

• Caution; not recommended
• It is unknown whether naloxone is excreted in human breast milk. Buprenorphine and its metabolites are excreted in human breast milk
• In rats, buprenorphine has been found to inhibit lactation. Therefore, breastfeeding should be discontinued during treatment with Buprenorphine/Naloxone

Fertility

• Animal studies have shown a reduction in female fertility at high doses (systemic exposure >2.4 times the human exposure at the maximum recommended doses of 24 mg buprenorphine)

Renal Impairment

• Severe: Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated

Elderly

• Caution; no information available

Porphyria Information

• Naloxone: Probably porphyrinogenic (PRP)
• Buprenorphine: Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - In competition

Central Nervous System Disorders

• Headache
• Migraine
• Dizziness
• Hypertonia
• Paraesthesia
• Somnolence
• Amnesia
• Hyperkinesia
• Seizure
• Speech disorder
• Tremor
• Syncope
• Insomnia
• Anxiety
• Depression
• Decreased libido 
• Nervousness
• Abnormal thinking 
• Abnormal dreams
• Agitation
• Apathy
• Depersonalisation
• Drug dependence
• Euphoric mood
• Hostility
• Hallucination

Cardiovascular Disorders

• Angina pectoris
• Bradycardia
• Myocardial infarction
• Palpitations
• Tachycardia

Respiratory Disorders

• Cough
• Asthma
• Dyspnoea
• Yawning
• Bronchospasm
• Respiratory depression

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting
• Abdominal pain
• Diarrhoea
• Dyspepsia
• Flatulence
• Mouth ulceration
• Tongue discolouration

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Hepatic necrosis
• Hepatorenal syndrome

Genitourinary Disorders

• Urine abnormality
• Albuminuria
• Dysuria
• Haematuria
• Nephrolithiasis
• Urinary retention
• Erectile dysfunction
• Amenorrhoea
• Ejaculation disorder
• Menorrhagia
• Metrorrhagia

Endocrine and Metabolic Disorders

• Decreased appetite
• Hyperglycaemia
• Hyperlipidaemia
• Hypoglycaemia

Musculoskeletal Disorders

• Back pain
• Arthralgia
• Muscle spasms
• Myalgia
• Arthritis

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Pruritus
• Rash
• Urticaria
• Acne
• Alopecia
• Exfoliative dermatitis 
• Dry skin
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Leukocytosis
• Leukopenia
• Lymphadenopathy
• Thrombocytopenia
• Hypersensitivity
• Anaphylactic shock
• Influenza
• Infection
• Pharyngitis
• Rhinitis
• Urinary tract infection
• Vaginal infection

Sensory Disorders

• Amblyopia
• Lacrimal disorder
• Conjunctivitis
• Miosis
• Vertigo

Others

• Drug withdrawal syndrome
• Neonatal drug withdrawal syndrome

• CYP3A4 inhibitors
• CYP3A4 inducers
• Central nervous system depressants
• Benzodiazepines
• Opioid antagonists
• Monoamine oxidase inhibitors

None routine. Specific cases may require

• Hepatic function

• Treatment must be under the supervision of a physician experienced in the management of opiate dependence/addiction
• Medical withdrawal: After a satisfactory stabilisation has been achieved, and if the patient agrees, the dosage may be reduced gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. Patients should be monitored following medical withdrawal because of the potential for relapse

Buprenorphine
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ and κ (kappa) opioid receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible properties with the μ-opioid receptors which, over a prolonged period, might minimise the need of addicted patients for drugs.

Naloxone
Naloxone is an antagonist at μ-opioid receptors. When administered orally or sublingually in usual doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect because of its almost complete first pass metabolism. However, when administered intravenously to opioid-dependent persons, the presence of naloxone in the buprenorphine/naloxone combination product, produces marked opioid antagonist effects and opioid withdrawal, thereby deterring intravenous abuse.

COMBINATION PREPARATIONS

Naloxone/ Buprenorphine

Tablet sublingual 0.5mg/2mg

• Suboxone (Adcock Ingram) originator

Tablet sublingual 2mg/8mg

• Suboxone (Adcock Ingram) originator