Fentanyl, a synthetic opioid previously available for parenteral use in anesthesia (Sublimaze), has now been marketed in a controlled-release transdermal formulation (Duragesic - Janssen) for use in patients with chronic pain severe enough to require opioid analgesia. It is not recommended for treatment of postoperative pain because of the drug's slow onset and prolonged duration of action.

Transdermal fentanyl (Duragesic, and others) offers a convenient delivery system for patients with chronic pain1 but it has some drawbacks. One is that exposing the patch to heat, either from an external source, increased exertion or possibly high fever, could increase release of the drug, which might lead to an overdose and fatal respiratory depression.2 A recent article in the NY Times about this problem may have aroused the concerns of some patients using the patches.3First approved for marketing by the FDA in 19914, transdermal fentanyl provides continuous delivery of the drug for about 3...

The FDA has approved the partial opioid agonist buprenorphine in a transdermal formulation (Butrans – Purdue) for treatment of moderate to severe chronic pain. Buprenorphine has been available in the US for years in parenteral formulations for pain and in sublingual tablets for opioid dependence.1 Transdermal buprenorphine has been available in Europe for several years.2

Nalmefene (Revex - Ohmeda), an i methylene analog of naltrexone (Trexan), is a long-acting opioid antagonist that has been approved by the US Food and Drug Administration for reversal of postoperative opioid drug effects, including respiratory depression, sedation and hypotension and for management of known or suspected opioid overdose in the emergency department. The only other opioid antagonists available in the USA are naloxone (Narcan), which is also injectable but has a short duration of action, and naltrexone, which has a long duration of action but is marketed only for oral...

The Medical Letter review of Palladone (hydromorphone HCl) extended-release capsules (March 14, 2005) warned that a lethal dose could be released if the new formulation was taken with alcohol. Because of that risk, the FDA asked the manufacturer (Purdue) to withdraw the drug from the market (FDA News. July 13, 2005; FDC Reports – “The Pink Sheet” July 18, 2005; 67:3).

A once-daily extended-release (ER) oral formulation of the opioid analgesic hydromorphone hydrochloride (Palladone - Purdue Pharma) has been approved by the FDA for treatment of opioid-tolerant patients with persistent moderate to severe pain. Hydromorphone HCl, a semisynthetic congener of morphine and active metabolite of hydrocodone that has been used since the 1920s, is also available in immediate-release oral, injectable and suppository forms (Dilaudid, and others).

Fentanyl, a synthetic opioid previously available for parenteral use in anesthesia (Sublimaze, and others) and in a transdermal patch for chronic pain (Duragesic - Medical Letter, 34:97, 1992), has now also been marketed as a raspberry-colored lozenge on a plastic handle (Fentanyl Oralet - Abbott), which resembles a lollipop. The new formulation will probably be promoted mainly for premedication of children before anesthesia, but has also been approved by the US Food and Drug Administration (FDA) for preanesthetic use in adults and for use in anesthesia or 'monitored anesthesia care' in...

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

A new CDC guideline for prescribing opioids for pain recently became available. Nonopioid drugs for pain were reviewed in a previous issue.