Tips for starting medication in patients with opioid use disorder

Key takeaways:

• Buprenorphine for OUD is arguably safer to prescribe than common medications for other conditions, such as insulin, a presenter said.
• Patients can remain on buprenorphine for the rest of their lives.

SAN DIEGO — “Now more than ever,” physicians need to manage opioid use disorder with pharmacological treatment in the primary care setting, according to a speaker at the ACP Internal Medicine Meeting.

Previous research has shown that most patients with opioid use disorder (OUD) do not receive life-saving medication, and many primary care physicians are hesitant to prescribe it.

One barrier was the X wavier that physicians were required to obtain in order to prescribe medication — buprenorphine, specifically — for OUD. That requirement has since been waived, “so you are all ready to prescribe,” Ann R. Garment, MD, FACP, a clinical associate professor of medicine at New York University Grossman School of Medicine and medical director of the Primary Care Addiction Medicine Clinic, told attendees at the meeting.

Garment, who is also section chief of general and hospital medicine at NYC Health & Hospitals/Bellevue, said it is “personally satisfying” to help patients address their OUD, but it is also “needed on the population level.”

There have been three waves of opioid-related overdose deaths in the United States, she explained.

“The first started around 1999 when pain became to be considered as a vital sign. There was a lot of emphasis on addressing pain, and with that came this tremendous rise in prescriptions of opioids,” she said. “Then around 2010, when legislation went into effect that caused more restrictions on prescribing opioids, you saw a big increase in recreational heroin use. We are now unfortunately in the third wave of overdose deaths, which are largely due to synthetic opioids. What we’re really talking about here is fentanyl.”

Medication options for OUD

There are three medications for OUD: buprenorphine, methadone and naltrexone.

Buprenorphine is a partial agonist that is “incredibly safe” and can be prescribed by any PCP in the outpatient setting, Garment said.

“I’m going to argue that buprenorphine is safer to prescribe than coumadin and insulin. It is a no-brainer,” she said. “Everyone should feel they can prescribe this medication.”

The reason why buprenorphine is a safe medication is because it is a partial agonist with a “ceiling effect” that prevents patients who take higher doses from experiencing an escalation in opioid effects, Garment said.

“You’re not going to see respiratory depression. You’re not going to see overdose and death,” she said. “This is a medication that is going to treat opioid use disorder, but you are not going to get bad side effects from it.”

Buprenorphine is also “a very sticky medication” with a high affinity for opioid receptors, Garment said.

“If you are taking buprenorphine and you decide you’re going to go out and use some heroin, the buprenorphine is going to be more tightly bound to your opioid receptors than that heroin would be, and it will block the heroin from those receptors,” she said. “And so, there’s some built-in protection in there. It is harder to use recreational opioids on top of buprenorphine if you already have buprenorphine in your system.”

Finally, buprenorphine is considered safe because most formulations are combined with naloxone, which helps prevent overdoses if patients attempt to use buprenorphine recreationally.

“If you wanted to try to get high from buprenorphine ... you could theoretically take it, crush it up and inject it,” Garment said. “The reason it is co-formulated with naloxone is because if you did that with buprenorphine and naloxone, the naloxone would then cancel out the buprenorphine and you would not be able to use it that way.”

Methadone, a full agonist for OUD, is another medication option. Most physicians do not prescribe it since it can only be dispensed at opioid treatment programs (OTPs), which “have very strict regulations,” Garment said. Methadone for OUD cannot be dispensed at an outside pharmacy.

The third medication option for OUD, naltrexone, is a full antagonist.

Most naltrexone doses are prescribed as a monthly long-acting injectable, as current evidence suggests that the oral formulation “is not great compared to injectables,” Garment said.

The drug is associated with several potential adverse events, including injection site reaction and potential mood changes, as well as dizziness and nausea, especially with the first dose, Garment said. There are also questions about liver function abnormalities, “but that really is literature that has much more to do with oral naltrexone and higher doses and is really not seen with this injectable,” she said.

In addition, “there are two big challenges” with naltrexone, according to Garment.

One is loss of tolerance to opioids, making patients potentially at risk for overdose “if they go back to using the way that they had before,” she said.

It is also difficult to start patients on naltrexone since they must fully detox before receiving the treatment, which Garment said takes at least 7 to 10 days. In contrast, buprenorphine typically requires a withdrawal period of 1 to 2 days before initiation, and methadone requires no withdrawal.

Clinical pearls for prescribing buprenorphine

Garment urged attendees to start buprenorphine “as soon as possible for anyone who is interested.”

Buprenorphine is available as a tablet or film. While most patients receive a combination product with naloxone, a monotherapy product is available for those who have a reaction to naloxone.

Injectable buprenorphine is also now available as a monthly injection, which many insurance companies cover. However, since the injectable is a controlled substance that requires refrigeration, physicians will need to keep it in a locked refrigerator. Garment said that her patients who received injectable buprenorphine “like the fact that they do not need to take medication every day.”

“They stopped thinking about their opioid use disorder every day. They just feel normal,” she said. “It’s really an exciting alternative that’s on the horizon for mass availability.”

Before patients can take their first dose of buprenorphine “they must be in mild to moderate opioid withdrawal” in order to avoid experiencing precipitated withdrawal, Garment said.

“For most patients, the conversation I’m having is, ‘wait until you feel really bad. Wait until you have goosebumps and some diarrhea, and your eyes are dripping and you kind of want to jump out of your skin. That’s when you can start this medication.’”

Typically, this takes about 12 hours for patients who are using a short-acting opioid and 24 hours for those on a long-acting opioid analgesic.

For patients who want to switch from methadone to buprenorphine, the withdrawal period between medications is about 72 hours, according to Garment. Most patients should be down to 30 mg or 40 mg of methadone, she added.

For patients who use heroin with fentanyl, the amount of time that it takes the drugs to get out of their system “is very variable,” so physicians “need to go based on symptoms,” Garment said.

When selecting a starting dose for buprenorphine, Garment suggested prescribing an 8 mg sublingual film that patients can cut in half. The general idea, she said, “is to take a little bit and see how you feel.”

“If you feel good, that’s your dose,” she said. “If you don’t feel good after a few hours, take some more and see how you feel.”

Garment encouraged physicians to have an office staff member call the patient the day after initiation to check in, then follow up in the clinic or over the phone in about 1 week to adjust doses if necessary.

Most patients will need around 16 mg daily, Garment said, adding “there is no goal to get them on the lowest dose possible.”

“The goal you’re aiming for is the dose that makes them comfortable and least likely to use other opioids,” she said.

Patients do not need a urine toxicology screen or other laboratory tests before receiving buprenorphine, according to Garment. If patients receive a urine toxicology screen and test positive for other drugs, she said this is not a reason to discontinue buprenorphine.

“If your patient is using other drugs, whether it’s benzos or stimulants, you absolutely can and should continue prescribing buprenorphine,” she said. “It is fine to be using other drugs with this because it is better to be using buprenorphine and other drugs than to be using, for example, heroin and other drugs.”

Patients should remain on buprenorphine treatment for at least 1 year, “if not forever,” she said.

If patients insist on discontinuing buprenorphine, Garment warned that the relapse rate is very high.

“This is a chronic health condition just like diabetes, just like hypertension. Most people will need lifelong treatment, and that’s totally okay,” she said. “We have great long-term data now showing that buprenorphine taken over the long term is perfectly safe and is a lot better than using other opioids long term.”

Garment said that patients who still have opioid cravings while receiving buprenorphine should consider switching to naltrexone.