Short- or Long-Acting Opioids: Which Is Best for Which Patient?

When a physician decides that an opioid analgesic is indicated for pain control, one of the next decisions to be made is whether to prescribe a short- or long-acting preparation. Although this seemingly should be a relatively straightforward decision, I’ve seen the wrong choice made many times and the effect is has on patients. There are guidelines to follow, however, that can help ensure timely and effective pain control.

Most oral opioids, including morphine, hydromorphone, oxycodone, oxymorphone, tramadol, and tapentadol, are now available in both short-acting (SA) and extended-, continuous-, or sustained-release (SR) forms. Of the commonly prescribed opioids, codeine and hydrocodone are available only in SA forms. An extended-release form of the latter is in development. For the short-acting agent meperidine, now widely contraindicated because of its poor adverse event profile and relative impotence, there is no call to develop a long-acting version.

Two opioids, methadone and levorphanol, are only available in pharmacologically long-acting forms, determined by their respective half-lives. (The SR nature of otherwise short-acting opioids is the result of an embedded delivery system that releases a pill’s active ingredient over time.) Once, levorphanol and methadone were the only long-acting opioids available. Today, levorphanol is rarely prescribed. It is used so infrequently that when the FDA recently introduced its Risk Evaluation and Mitigation Strategy (REMS) program covering all the LA and SR opioids, it overlooked levorphanol despite its ongoing availability in the US.
 
Fentanyl and buprenorphine differ from the other opioids in several ways. Both are available in oral forms that are absorbed through the buccal mucosa. The SA forms of fentanyl (Actiq, Fentora, Onsolis) have a rapid onset of action and are only FDA approved for the treatment of breakthrough pain in patients with cancer who are already taking opioids. Oral buprenorphine (Subutex, Suboxone) is only indicated for managing opioid dependence. Both fentanyl and buprenorphine are available in ER forms as transdermal patches (Duragesic, Butrans) that are indicated for controlling moderate to severe pain.

Decision Guidelines
There are a few basic rules that make it easy to decide whether to choose an SA, LA, or SR preparation when an opioid is indicated:
• For acute pain, always start with an SA opioid. Since it usually takes several days for LA and SR opioids to produce optimal analgesia, they make no sense for a patient in acute distress. Furthermore, if the initial SA dose does not provide sufficient relief, you can titrate quickly by prescribing additional doses. With LA and SR formulations, it takes a few days to determine if the dosage is sufficient.
• Opioid-naive patients should always be started on an SA opioid. You don’t yet know how the patient will tolerate and metabolize the drug. It is much safer, therefore, to prescribe an SA formulation that will be cleared from the patient’s body relatively quickly. 
• Once you know that the SA opioid is working and have decided that continued opioid therapy is indicated, it’s time to consider switching to an LA or SR opioid. The decision is primarily based on the frequency and timing of the pain, and how often the patient needs the opioid to control it. For patients whose pain is present throughout the day with little fluctuation (except when taking the opioid), and therefore need the SA opioid multiple times daily, a nLA or SR drug will usually provide more stable analgesia and is preferable. My rule of thumb is that if a patient needs to take an SA opioid more than twice daily every day, switch to a nLA or SR opioid.

Caveats
Here are a few caveats to keep in mind when starting treatment with an LA or SR opioid:
• Because of the time needed for an LA or SR opioid to establish analgesia, provide the patient with a prescription for an SA opioid (“rescue” medication) to manage breakthrough pain. This also provides coverage should you find in a few days that the LA/SR dosage needs adjustment. Once the LA or SR opioid has had enough time to provide sustained analgesia, the need for additional SA opioid is a useful guide to determine whether you need to increase the dose of the LA or SR. Ideally, when the pain is being controlled, the patient should rarely need the SA opioid.
• There is no fail-safe guide to which LA or SR drug to choose. All are effective. Some doctors prefer to prescribe the SR form of the SA drug that the patient started with. This rationale is logical, as the physician can get a clear idea of what SR dosage will be needed based on the patient’s response to the SA dosage.
There are only 2 scenarios that would lead me to choose against this rule: 
• The first instance is if the patient has trouble taking an oral opioid because of problems with swallowing or vomiting. In that case, I’d choose the transdermal fentanyl patch.  Because the SA forms of fentanyl are only indicated for breakthrough pain in patients already taking an opioid, it would not be possible to convert from one of these rapid-acting agents to the patch. Conversion from other opioids to transdermal buprenorphine can be difficult because of its potential to cause withdrawal.
• My second exception concerns methadone, which I find to be the most effective of all the LA or SR opioids. I frequently prescribe this when the patient needs prolonged pain control.