Managing LAIB: Dosing

Cracking Addiction this week

Once a patient has commenced on an LAIB it is important to be able to manage doses as well as knowing how to wean and or cease LAIB if required.

Dose titration of Buvidal
Because of the wide range of dosing options dose titration of Buvidal may occur. The following should guide considerations regarding dosing and titration. Buvidal doses should be maintained if the patient remains abstinent from opioids, and is not experiencing cravings, withdrawals or side effects. Dose reduction should occur if the patient experiences side effects, or is concerned about treatment, or otherwise wishes to cease treatment. The dose of Buvidal should be Increased if the patient experiences persistent drug use, cravings or withdrawal symptoms, but is free of side effects.

Top up doses for Buvidal
After induction, Buvidal weekly 8 mg doses can be administered at least 24 hours after the last injection to a maximum cumulative dose of 32mg per week.

Choice of Buvidal dosing
Patients may prefer monthly doing of Buvidal to facilitate a less intense therapeutic monitoring regimen. However, some patients may benefit from remaining on a Buvidal weekly schedule either by choice, or because of a desire for more frequent clinical review. This might be indicated for psychosocial reasons (trauma complex psychological comorbidity), medical comorbidities (cardio-respiratory disease, hepato-renal disease), or the concomitant use of other hypno-sedatives, including benzodiazepines, alcohol or other drugs.

Top-up doses for Sublocade
"Top up" dosing on top of Sublocade can be provided in the form of sublingual buprenorphine. The recommended maximum dose is eight mg daily for a maximum of 14 days.

Sublocade maintenance
After the recommended loading dose of Sublocade 300 mg monthly for first two months the usual maintenance dose is 100 mg monthly. High dose maintenance with Sublocade 300 mg provides no proven additional efficacy but does risk a higher incidence of adverse events. Nonetheless high dose Sublocade maintenance may be considered for patients who have previously stabilised on high doses of SL BPN (e.g. 24 to 32mg daily), or who experience cravings or unsanctioned opioid use during the first 2 months of induction.

Dose titration
Dose titration refers to the process refining doses after induction, which usually takes place during early maintenance. Post titration, doses of LAIB should be maintained if the patient is abstinent, without cravings, withdrawals and side effects, and if the patient is satisfied. Doses of LAIB might be reduced if the patient experiences side effects or if the patient has concerns, or if the patient wants to cease treatment. Doses of LAIB might be increased if the patient experiences persistent drug use, cravings or withdrawal symptoms without side effects. Doses of LAIB may need to be increased if patients are co-administered CYP 3A4 enzyme inducers such as carbamazepine and upon cessation of treatment with such medication the dose of LAIB may need to reduce.

Timing tolerances
During the LAIB maintenance phase it is important to consider dose timing tolerances. Buvidal weekly has a timing tolerance of 7 days +/- 2 days and therefore can be administered every five to nine days. Buvidal monthly has a timing tolerance of 4 weeks +/- 1 week, which means it can be administered every three to five weeks. Sublocade at both the 100 mg and 300 mg dose has a timing tolerance of 28 days – 2 days, + 14 days, so therefore can be administered every 26 to 42 days.

Delayed dosing
If it can be anticipated that, for whatever reason, the next dose of LAIB can only be scheduled outside the relevant timing window of that LAIB then dosing with interim sublingual buprenorphine may be used until the next LAIB dose can be administered. In the case of Buvidal the dose of sublingual buprenorphine should be calculated according to the standard dosing equivalency chart. In the case of Sublocade then a dose of at least 8 mg daily of sublingual buprenorphine may be used for a maximum of 14 days. This dose may be titrated according to clinical need.

Missed doses
The long tail associated with all LAIB needs to be considered when managing missed doses of LAIB. After steady state has been reached some patients may still feel well controlled after three weeks of Buvidal weekly, after three months of Buvidal monthly, after two months of Sublocade 100 mg, and after five months of Sublocade 300 mg. Clinical judgement is required to determine whether or not a patient needs to be re-inducted as per usual protocols or whether or not the previous dose of LAIB can be continued.

Switching

Switching from Buvidal weekly to monthly or vice versa.

Switching between weekly or monthly doses of Buvidal should be performed with due consideration of the dosing chart above. During switches the patient should be monitored for cravings and withdrawals and doses should be titrated as needed.

Switching from Sublocade to Buvidal
When switching from Sublocade 300mg monthly to Buvidal the patient should be transferred to high dose Buvidal (either 32 mg weekly or 128 mg monthly). During this process, the patient should be monitored closely for withdrawals or cravings. It should be noted that if that patient has been stabilised on Sublocade 300 mg then delayed withdrawal (even up to five months after cessation of Sublocade) may occur. When switching from Sublocade 100mg monthly, the patient should be transferred to moderate doses of Buvidal (24 mg weekly, or 96 mg monthly). Whilst the patient should be monitored for withdrawals, they are less likely to occur when switching from Sublocade 100 mg as compared to a switch to Buvidal from Sublocade 300 mg.

Switching from Buvidal to Sublocade
Patients who have been stabilised on Buvidal but need to switch to Sublocade should be transferred to Sublocade 100 mg. The two 300 mg "induction doses" of Sublocade are not required unless the patient was experiencing significant withdrawals or cravings despite being stabilised on Buvidal 128 mg monthly.

Cessation: Withdrawing from depot injections
Patients can have many reasons for wishing to cease treatment with LAIB. Treatment failure may unfortunately be one of those reasons. Treatment failure can be characterised by ongoing cravings, withdrawals, and persistent illicit opioid use despite maximal doses of LAIB at steady state with optimized psychosocial interventions. Further therapeutic options can include the following: abstinence, a desire to transfer to sublingual buprenorphine or methadone. At LAIB steady state buprenorphine plasma concentrations decrease slowly over time which means that therapeutic levels may be maintained for extended periods of time.