Pain Management in Hospice Patients: Buprenorphine (Subutex, Suboxone)
Posted by Dr. Jim Joyner
Buprenorphine (Subutex, Suboxone) tablets are now being used to treat severe pain, not just opioid addiction. Since 2002 Buprenorphine has been widely used to treat opioid addiction by preventing the symptoms of opioid withdrawal.
More recently it is being used to treat severe pain, although the tablets only have an FDA approved indication for addiction treatment at this time. Subutex contains buprenorphine alone, and Suboxone contains buprenorphine and naloxone. The naloxone is there to prevent opioid effects if patients try to inject it.
Buprenorphine is a strong opioid with analgesic properties similar to morphine, methadone, oxycodone, hydromorphone, and fentanyl. It has an advantage over these traditional full agonist opioids in that there is less risk for psychological or physical dependence and it results in fewer withdrawal symptoms when it is stopped. There is also less risk for psychotomimetic effects (delusions, hallucinations). The FDA has recognized the lower risk factor for abuse with Buprenorphine and has assigned it a Schedule III controlled drug classification as opposed to the more stringent Schedule II classification seen with other strong opioids.
Some subtle differences in Buprenorphine pharmacology may account for the decreased risks seen when comparing to more traditional strong opioids. Drugs such as Morphine, Methadone, Fentanyl and others are full-agonists at the mu opioid receptor which means they bind tightly to the drug receptor sites in the body. Withdrawal of therapy for drugs with complete and tight binding at their receptor sites is associated with significant withdrawal symptoms. Buprenorphine is a partial-agonist the mu opioid receptor and is actually an antagonist at the kappa opioid receptor. It essentially is loosely bound to the mu receptor. This partial agonist property and the mixed agonist-antagonist activity may result in a decreased potential for abuse, withdrawal, and psychotomimetic effects in patients using Buprenorphine.
Subutex and Suboxone are available in tablets for sublingual administration. They are not effective by the oral route. Strengths are 2mg and 8mg tablets. The dosage range is 2 to 16mg three to four times a day for pain (instead of once a day for addiction treatment). Unlike traditional full-agonist strong opioids (morphine, methadone, fentanyl, oxycodone, and hydromorphone), Buprenorphine seems to have a "ceiling dose" after which increased doses produce no increase in opioid agonist effects.
This was demonstrated in clinical trials at doses of 16 to 32mg. The onset of action of the tablets is about 15 minutes, with peak activity at 60 minutes and a duration of analgesic activity of 6 to 8 hours. There is also an injectable solution available for intramuscular or intravenous administration. This injectable solution carries an FDA approved indication for the treatment of severe pain. The IM/IV dosage is 0.3mg at six hour intervals as necessary. IV doses should be administered slowly over 2 minutes.
The cost of a 15 day supply of a mid-range dose of Subutex (4mg three times per day) is in the range of $360.00. This makes Subutex one of the highest, if not the highest cost opioid drug on the market. The role of Buprenorphine in the management of chronic pain is still being defined. It has some significant advantages including: a lower potential for psychotomimetic side effects, lower abuse potential, reduced potential for severe withdrawal reactions, and no requirement for a schedule II triplicate prescription. Due to the fact that its duration of action is only 6 to 8 hours, Burprenorphine does not have the characteristics of a desirable long acting opioid that one would use for maintenance therapy of severe chronic pain. The greatest negative is the extremely high cost which makes it an unrealistic option for most hospice organizations at this time. The evolving role for Buprenorphine in the management of pain may be one that is targeted at acute severe pain in the hospital and clinic setting.