The opioid agonists methadone and buprenorphine have been the mainstays of opioid dependence treatment in Australia for decades—but the required daily trips to the pharmacy have been particularly difficult for many patients, both because they can add to the stigma they perceive, and because of the disruption to their daily activities—especially as rates of problematic opioid use are higher in rural and regional areas.
However, two long-acting injectable buprenorphine formulations are now approved for the treatment of opioid dependence which may help address these barriers to treatment, according to Dr Adam Straub, addiction medicine and general medicine physician.
Methadone is a full opioid agonist that activates all three opioid receptors, and the bigger the dose, the bigger the effect. Methadone usually takes several weeks to achieve the appropriate dosage and comes with some risks.
Over-sedation and respiratory depression can occur if it’s used in combination with other sedating substances such as benzodiazepines, alcohol and gabapentinoids, Dr Straub says.
Prolonged QTC syndrome is a rare adverse effect that’s more likely to occur in doses over 100 mg.
Methadone also interacts with anything that involves the cytochrome P450 system (e.g. furosemide, amiodarone, sotalol or carbamazepine).
Two long-acting injectable buprenorphine formulations, Buvidal and Sublocade, were listed on the PBS in 2020 for the treatment of opioid dependence.
They now make up around 25% of all medication assisted treatment for opioid dependence (MATOD) in Australia, Dr Straub says.
Both products have much longer half-lives, Dr Straub says. Buvidal Weekly has a half-life of three to five days, while Buvidal Monthly has a half-life of 19 to 25 days. Sublocade has a half-life of 43 to 60 days.
Benefits include greater convenience with shorter wait-times, less frequent visits to clinics or pharmacies and reduced feelings of stigma, Dr Staub says.
“They don’t have to sit in our waiting rooms that often, with the concerns about ‘who else is around me, who’s seeing me here to see that doctor. Do they know why I’m here?’”
“People don’t have to worry about going back to the pharmacy every few days or every week. They can travel if they need to.”
But patients do need to be aware that the injectables are difficult to reverse.
“Once they’re in, they don’t come out,” Dr Straub says.
Sublocade comes in two monthly doses: a 300mg dose in 1.5mL, and a 100mg dose in 0.5 mL with a 19-gauge needle.
Sublocade is a simpler dosing regimen, Dr Staub says. Typically, it starts with two 300mg loading doses, one month apart. Depending on the patient, they can continue at that dose or reduce to a 100mg maintenance dose.
Sublocade requires at least 26 days between doses.
Buvidal comes as a pre-filled syringe with doses between 0.16mL and 0.64mL and uses a fine 25-gauge needle, Dr Straub says.
“Buvidal is a little bit more complex, but it has a bit more finesse capability,” Dr Staub says.
“You’re able to titrate up and down depending on the patient and where they are in their opioid agonist treatment.
Another difference is that Buvidal is authorised to initiate directly, without first stabilising on sublingual buprenorphine.
Buvidal Weekly takes about 24 hours to reach peak concentration, Dr Straub says.
Compared with sublingual buprenorphine it has a lower likelihood of precipitated withdrawal—but the risk increases if the injection is given before the patient is in withdrawal. “That can happen if you give it a little bit too early or if your patient hasn’t told you the last time they actually dosed,” Dr Straub notes.
If possible, patients should be in mild to moderate withdrawal with clear signs of withdrawal present before initiating Buvidal, he says.
“Ideally, at least six hours after the last dose of short acting opioid.”
Again, patients should be in mild to moderate withdrawal first.
“If you can, have your patient delay that injection as long as possible before that first dose,” Dr Straub says.
“Buvidal Weekly’s slow onset to peak concentration time allows for adjustment around longer acting opioids with reduced risk of precipitated withdrawal.”
Methadone is a very long-acting full opioid agonist, so it does increase the risk of withdrawal, Dr Straub says. National guidelines recommend tapering methadone to 30mg per day before commencing weekly Buvidal.
“Ideally, our patient should wait at least 24 hours after their last methadone dose before they have their first injection.”
Patients can move from weekly to monthly injections whenever they feel comfortable, he says, noting that you can top-up the monthly with weekly doses if needed.
Ideally, patients would be transitioned through sublingual buprenorphine before moving to long-acting injectable buprenorphine, Dr Straub says.
“That being said, not every patient can tolerate the withdrawal effects when reducing methadone. We need to be prepared for the eventuality that they may not make it down to 30mg to facilitate the smoothest transfer. It may benefit the patient and the prescriber to involve local addiction medicine services to help guide the transition in these instances.”
Discuss the risks and benefits of each product with the patient, and the tailoring that’s possible with dosing of MATOD products, Dr Straub says.
Each patient’s previous experience with opioid agonist treatments and their social circumstances should be considered, he says.
“Is this somebody who’s going to have a hard time getting to and from the chemist? Do we need to delay the doses in between? Do we need to make sure we have as much coverage as we can?
“Is it somebody who wants to have a lot more control over their dose, and do we need them on weekly doses because they want to fiddle with it really finely? We need to think about all those things.”
Patients will feel vulnerable if changes are made to medications they’ve been using for a long time, so it’s important to plan for the conversation, consider what else is going on in their life, including psychosocial issues, he says. “The important thing is to have an open and frank conversation without judgment, knowing that the person in front of you is scared and vulnerable.”
Pharmacists in most places in can administer the medications, but check to make sure there is an appropriate dispensing location.
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