Vivitrol (extended-release naltrexone)

Vivitrol is naltrexone in a syringe, given once a month in your butt. That’s the whole pitch. If you’ve read the naltrexone post, you already know what the drug does in your brain. This one is about why the injection version is sometimes the right move and sometimes a waste of money.

The active ingredient is the same molecule. The dose is 380mg suspended in a slow-release microsphere formulation, which is a fancy way of saying tiny plastic-ish beads that dissolve over a month and let the drug out gradually. You get it injected into the gluteal muscle, it releases over about four weeks, and during that time you have therapeutic levels of naltrexone in your system whether you remember to think about it or not. That’s the entire reason this product exists. Adherence. The pill works fine if you take the pill. The pill doesn’t work if it stays in the drawer.

Why the shot beats the pill, sometimes

For alcohol use disorder, the daily pill works fine if you take it. The trouble is the people who most need this medication are often in the worst part of their drinking, and the worst part of your drinking is not when you’re great about remembering daily medications. Studies show that about half of people prescribed daily naltrexone are still taking it at three months. The other half drift off, usually after a bad week, and the medication can’t help them if it’s sitting next to the ibuprofen in a kitchen drawer.

Vivitrol removes that step entirely. You show up at the clinic on the same day each month, somebody injects you, and you don’t think about it again until the next appointment. For guys who are pattern-strong and pill-weak, it’s a real upgrade. For guys whose wives have been checking the pill bottle, it removes the daily conversation entirely, which sometimes turns out to be the actual selling point because the daily conversation was its own weight on the marriage.

For opioid use disorder, the math is different and the stakes are higher. Vivitrol is one of three FDA-approved medications for opioid use disorder. The other two are buprenorphine, a partial opioid agonist that goes by the brand Suboxone, and methadone, the full agonist that requires going to a clinic. Vivitrol is the antagonist, meaning it blocks the receptors entirely instead of activating them. Which one is right for you depends on a long conversation, but the short version is that Vivitrol works if you can get through the seven-to-ten day washout period needed before the first dose, and stay engaged enough to come back every month for the next year or two. If either of those is shaky, buprenorphine is usually a better bet, because Suboxone lets you start almost immediately and doesn’t punish you for missing a day.

The washout problem

You cannot start Vivitrol while you have opioids in your system. If you do, you’ll go into precipitated withdrawal within hours, and it is genuinely worse than regular withdrawal. We’re talking projectile vomiting, full body tremors, soaking sweats, gut cramps, and the kind of misery that makes people swear they’re never going through that again. For alcohol patients, this is not relevant. For opioid patients, it’s the main hurdle.

Practically, this means a guy coming off heroin or fentanyl needs to be opioid-free for at least seven days, sometimes ten or fourteen, before the first injection. Those are the exact days when people relapse. We sometimes admit guys to an inpatient unit just to bridge that window, not because the medical management of it is hard, but because being home with the phone and the dealer’s number in it and a week of misery to get through is asking too much of somebody who has been losing this fight for years. We also use clonidine and comfort meds to help take the autonomic edge off, the sweating and gut cramps and racing heart. It’s still hard. It’s the hardest part of the protocol and it’s the reason a lot of patients can’t make it to Vivitrol even when they want to.

What’s nice to hear about this one

If we’re being honest, the Vivitrol math at its best is pretty good. The kind of guy who comes in having been through detox four times, longest stretch clean was eleven months, tried buprenorphine and hated the foggy feeling, wife already took the kids back to her parents once and warned him there isn’t a third time, can get through the washout in a partner inpatient program, take his first injection on day eight, and come in monthly for two years. About eighteen months in, the appointments start to feel pro forma. Not because he’s slipping, but because he kind of forgot he had a problem. That’s the result you want. The drug stops being the thing, the marriage stops being the thing, the work and the new job and the kid’s basketball games are the thing. That’s a real arc. Nobody’s running an ad about it because the arc is boring to watch, but it’s a real arc.

If the pill keeps ending up in the kitchen drawer instead of in your mouth, the injection solves the part of the problem your willpower can’t.

Side effects and the injection itself

The injection is into the gluteal muscle and it stings going in. There’s a lot of liquid going into the muscle and it is not subtle. Some patients get a knot at the injection site that lasts a few days. Rarely it gets infected and we have to deal with it, which usually means antibiotics and a couple of days of warm compresses, not anything dramatic. The drug itself has the same side effect profile as oral naltrexone… occasional nausea, occasional headache, very rarely some elevation in liver enzymes that we monitor with periodic labs.

The injections alternate cheeks. You’ll learn to schedule your appointment for a day you’re not planning to ride a bike or sit on a hard surface for long, which is funnier than it sounds the first time a patient asks if it’ll affect his weekend.

Where the field gets this wrong

Most patients who get Vivitrol get it because they walked into a clinic that already prescribes it and asked. Most patients who would benefit from it never hear about it, because their primary care doctor doesn’t prescribe injections, their addiction counselor is suspicious of medications in general, and the rehab they went to twelve years ago handed them a coffee mug and a list of meetings. The treatment landscape in this country is still organized around the idea that the work is going to AA and the medication is optional and slightly suspect, instead of the actual evidence, which is that medication-assisted treatment outperforms abstinence-only by a wide margin and the right answer is usually both at once.

The X:BOT trial, which compared Vivitrol head-to-head with buprenorphine for opioid use disorder, is worth knowing about. Once patients actually started Vivitrol, the two drugs performed about the same. The catch was that fewer patients made it through the washout to start the injection in the first place. So if you can get there, the data is solid. The whole hard part is getting there.

Cost

List price is around $1,500 per injection. Insurance often covers it, especially since the ACA pushed addiction parity rules. Medicaid in Oregon and Washington usually covers it for opioid use disorder, sometimes more grudgingly for alcohol use disorder. If you’re paying cash, this gets expensive fast, and the math stops making sense pretty quickly compared to the generic pill. There’s a manufacturer copay program that drops the cost substantially for commercial insurance patients. Use it. It’s one of the few patient-assistance programs that actually does what it says on the box without making you spend three hours on the phone.

On the autonomy piece

The honest version of this conversation is that nobody picks Vivitrol over the pill because they enjoy needles. They pick it because the daily decision has been killing them, or because the pill kept getting forgotten, or because the wife checking the bottle had turned into its own marital event. Patients should get the option laid out honestly. If you want the pill, you get the pill, my job is the take, your job is the choice. The most I’ll do is name the pattern… if you’ve already missed a week of pills twice in the last two months, that’s the data, and the data says the injection is going to do more for you than the pill will. Disapproving yes, if you want to keep trying the pill anyway. The appointment isn’t mine.

Bottom line

Vivitrol is the right answer when the pill is the problem. Same drug, fewer decisions, one appointment a month instead of thirty pill bottle moments. For opioid use disorder, you need to get through the washout first, which is the hard part. For alcohol, you can start it pretty much right away. It is a tool that solves a specific problem, the daily decision, and it solves it well. It doesn’t solve every problem… it doesn’t make you want to be sober, that part is still yours.

Sources

1. Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-1513. PMID 21529928.
2. Garbutt JC, Kranzler HR, O’Malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-1625. PMID 15811981.
3. Lee JD, Nunes EV, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT). Lancet. 2018;391(10118):309-318. PMID 29150198.