Opioid Analgesics: What's New?

Oral oxymorphone

Oxymorphone has been available in suppository and injectable forms (Numorphan) for many years, but based on my experience, these formulations are rarely prescribed. In fact, I cannot recall a case in which either form was used. There are now 2 new oral formulations of oxymorphone-an immediate-release (Opana) and an extended-release formulation (Opana ER).

Oxymorphone is a metabolite of oxycodone, which is available in immediate-release (Percolone, Roxico- done, OxyIR) and extended-release (OxyContin) forms and in immediate-release form in combination with non-opioid analgesics, including acetaminophen (Percocet), aspirin (Percodan), and ibuprofen (Combunox). Some clinicians may view the lack of availability of oxymorphone in combination with 1 of these other analgesics as a negative, but I would disagree. Actually, when prescribing immediate-release oxycodone, I usually prefer the single drug to the others. This avoids the risk of overdose of the combined medication if the dose of opioid needs to be increased, a frequent issue because many patients develop tolerance to the analgesic effects of opioids.

Oxymorphone is formed when oxycodone is metabolized through the hepatic cytochrome P-450 2D6 enzyme system. A certain amount of analgesia is provided by oxycodone and an additional amount is given by oxymorphone. The exact percentage of analgesia provided by each is unclear and probably varies among individuals.¹

Although the exact equianalgesic dose is unclear, dosing of oxymorphone is similar to the recommended dosing of oxycodone. The immediate-release formulation of oxymorphone is available in 5- and 10-mg doses; the recommended starting dosage is 5 to 10 mg every 4 to 6 hours (Opana package insert). The extended-release formulation is available in 5-, 10-, 20-, and 40-mg tablets and should be prescribed on a schedule of once every 12 hours (Opana ER package insert). As with oxycodone, I would recommend that all patients first take the immediate-release formulation of oxymorphone. Patients with continuous or frequent pain who need to take the medication multiple times during the day can then be switched to the extended-release form after proper dosing has been determined.

I am unaware of any published head-to-head studies comparing oral oxymorphone and the oxycodone formulations. It is thus impossible to predict, with one possible exception, which one will provide better analgesia to patients. The one exception is in patients who are taking a drug such as paroxetine (Paxil) or fluoxetine (Prozac), which inhibits the 2D6 isoenzyme. In these patients, oxymorphone would appear to be a better choice.

With regard to the drug's potential for the development of abuse and psychological dependence in patients, there is nothing to indicate that oxymorphone markedly differs from oxycodone or the other opioids.

Fentanyl buccal tablet

The fentanyl buccal tablet (FBT) (Fentora) resembles another fentanyl preparation that has been available for several years, the oral transmucosal fentanyl citrate (OTFC) lozenge (Actiq).

The major differences between these 2 drugs are that the new formulation has greater bioavailability and works more quickly. This is because compared with OTFC, more of the fentanyl is absorbed through the buccal mucosa and less is swallowed and absorbed through the GI tract. Approximately twice as much fentanyl is absorbed through the buccal mucosa with FBTs as with OTFCs.²

The new formulation has the additional minor benefit of being a tablet, unlike the older formulation, which is a lozenge on a plastic stick. Some patients feel self-conscious about having a plastic stick protruding from their mouth.

Both formulations are FDA-approved for the treatment of breakthrough pain in patients with cancer who are already taking and are tolerant of a strong opioid such as morphine (MS Contin, Oramorph, Roxanol), methadone (Dolophine, Methadose), transdermal fentanyl (Duragesic), or hydromorphone (Dilaudid) (see Fentora and Actiq package inserts). I have occasionally used the older formulation off-label in patients with chronic pain conditions who were taking 1 of these other medications but who had episodes of breakthrough pain so severe that they were unable to wait for the relief provided by an oral medication that was swallowed. Neither FBT nor OTFC should be used for the management of acute or postoperative pain, or as the primary opioid analgesic.

Both formulations should be used only up to 4 times daily. In patients who require more frequent administration, the dosage of the primary analgesic should be increased. FBT is available in 100-, 200-, 400-, 600-, and 800-µg tablets. Treatment should be started at the lowest dose, which should then be titrated if needed.

Tramadol extended-release tablet

Tramadol extended-release tablet (Ultram ER) is the once-daily dosing formulation of immediate-release tramadol (Ultram). Readers of this column are aware that tramadol has been highlighted as a useful medication in several recent pain guidelines, including those on the treatment of neuropathic pain and on musculoskeletal pain in patients with cardiovascular disease.^3,4

Despite this, I am not a strong supporter of the use of either form. Tramadol is a combination medication that includes a weak µ-opioid receptor agonist and a weak serotonin-norepinephrine reuptake inhibitor (SNRI).⁵ The major portion of the analgesia it provides appears to be caused by the latter action, and it is not surprising that tramadol has been found to be useful in pain conditions for which other drugs having SNRI actions, such as the tricyclic antidepressants duloxetine (Cymbalta) and venlafaxine (Effexor), are also effective. I prefer to prescribe duloxetine or venlafaxine instead of tramadol for 2 reasons. First, since they have stronger SNRI actions, they are more likely to have greater analgesic effects. Second, because tramadol contains an opioid, there is a risk of abuse and psychological dependence, although less than the risk associated with stronger opioids.

If a clinician chooses to prescribe extended-release tramadol, the immediate-release form should be started first and used to titrate the dosage before switching to the extended-release form.

Dr King is in the private practice of pain medicine in New York and is clinical professor of psychiatry at the New York University School of Medicine.

References:

References

1.

Prommer E. Oxymorphone: a review.

Support Care Cancer.

2006;14:109-115.

2.

Darwish M. Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate.

J Clin Pharmacol.

2007;47:343-350.

3.

Finnerup NB, Otto M, McQuary HJ. Algorithm for neuropathic pain treatment: an evidence based proposal.

Pain.

2005;118:289-305.

4.

Antman EM, Bennett JS, Daugherty A, et al. Use of nonsteroidal anti-inflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association.

Circulation.

2007;115:1634-1642.

5.

Hair PI, Curran MP, Keam SJ. Tramadol extended- release tablets in moderate to moderately severe chronic pain in adults.

CNS Drugs.

2007;21:259-263.