Global Awareness

On Cracking Addiction this week

The kinetics of first dose differ from that of steady state for all doses of both LAIB products. Troublesome symptoms of relative overdosing tend to abate within the first few days after weekly LAIB, and after the first two weeks of monthly LAIB as the plasma buprenorphine concentration rapidly falls to trough levels. Symptoms of withdrawal or craving associated with relative underdosing may emerge in the second half of a treatment window for both LAIB products early on in the journey to steady state. As steady state is achieved one can expect a reduction in the intensity of symptoms associated either with underdosing or overdosing.

It is important to warn patients that their experience of sublingual buprenorphine will be different to that of LAIB. Patients may interpret any symptom, including those of relative overdosing, or symptoms associated with any comorbid medical or psychiatric condition as opioid withdrawal. It is important to educate the patient regarding the symptoms of relative overdosing, and opioid withdrawal and to emphasise the need for adequate clinical assessment prior to diagnosing opioid withdrawal.

Dr Ferghal Armstrong has developed a useful mnemonic to conceptualise the symptoms of opioid withdrawal is “Army Finds” which demotes the following.

• Aches and pains
• Rhinorrhoea
• Mood disturbance
• Yawning
• Fever
• Insomnia
• Nausea and vomiting
• Diarrhoea
• Sweating

Buprenorphine demonstrates high avidity for the mu receptor. Therefore, it displaces other opioids from that receptor. It is a partial agonist of the mu receptor. So therefore, having displaced other full mu-agonists from the opioid receptor, it only partially agonises that mu receptor thereby causing an opioid withdrawal effect known as precipitated withdrawal.
When starting buprenorphine, it is important for patients to be already in withdrawal to avoid a worse precipitated withdrawal. Withdrawal can occur six to 12 hours after short acting opioids, such as heroin, codeine or oxycodone. But it may take 24 to 48 hours or even longer to manifest after exposure to long-acting opioids, including methadone. If we are to avoid precipitated withdrawal during induction of buprenorphine, we must administer buprenorphine only after withdrawal from other opioids has occurred. Therefore, we must recognize the signs and symptoms of opiate withdrawal.

The following are listed as contra-indications for both Buvidal and Sublocade.

Child-Pugh C liver disease
Respiratory insufficiency
Hypersensitivity to either buprenorphine or excipients

Contra-indications that are unique to Buvidal include.

Children less than 16 years of age
Acute alcoholism or delirium tremens
Pregnancy and lactation

Contra-indications unique to Sublocade include.
Subjects less than 18 years of age Acute intoxication with alcohol or other CNS depressants Pregnancy and lactation

Regarding review of the patient on LAIB this will depend on the formulation of LAIB chosen and expected treatment effect. It is a useful idea to review the patient regularly post commencing LAIB treatment and until patient has achieved a steady state of buprenorphine within their system. It is useful to review the patient 1-2 weeks prior to their second LAIB injection to ensure that the patient is progressing well and to trouble shoot any potential problems before they become significant issues.

On Cracking Addiction this week

This episode of Cracking Addiction is the first of a two-part series on Suboxone.

Suboxone is a combination of buprenorphine and naloxone which is administered sublingually as a form of opioid substitution therapy. Suboxone comes in two strength a 2mg buprenorphine/0.5mg naloxone and 8mg buprenorphine/2mg naloxone strength. The naloxone is not absorbed buccally or orally and if taken as intended the patient is only administered a dose of buprenorphine. Hepatic first pass metabolism prevents access of the naloxone into the systemic circulation though this can be impaired in severe liver disease such as Child Pugh C liver cirrhosis. In general, however naloxone does not become systemically active if Suboxone is taken as intended sublingually but if it is injected naloxone would antagonise the effect of any opioids within a patient’s system which could lead to an acute withdrawal syndrome.

Suboxone is an effective form of opioid substitution therapy taking between 30 minutes to four hours to reach peak plasma concentration from time of administration. Suboxone has a peak plasma concentration of 8.45ng/mL and average plasma concentrations of 2.91 ng/mL and trough plasma levels of 1.61ng/mL. It takes on average around 5-6 days to get to a steady state of buprenorphine with Suboxone. Suboxone has a half life of between 13-46 hours.

Thus one can see some of the benefits that are available in using Suboxone for opioid substitution therapy.