Pharmaceutical compositions
Pharmaceutical compositions are provided which comprise effective amounts of analgesic to treat a subject, including to reduce or eliminate an adverse effect associated with the analgesic.
1. A bi-layer tablet comprising (a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof; and (b) a controlled-release layer that comprises an opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.
2. The bi-layer tablet of claim 1 , wherein the opioid analgesic agent is hydrocodone bitartrate or oxycodone hydrochloride.
3. The bi-layer tablet of claim 1 , comprising from 1% to 20% by weight of the promethazine or a pharmaceutically acceptable salt thereof; from 10% to 80% by weight of the acetaminophen or a pharmaceutically acceptable salt thereof; and from 1% to 20% by weight of the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof.
4. A method for alleviating an adverse effect associated with administration of an opioid analgesic agent to a subject, the method comprising administering to the subject a bi-layer tablet comprising: (a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof; and (b) a controlled-release layer that comprises the opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.
5. A method for treating pain in a subject suffering from or susceptible to pain, the method comprising administering to the subject a bi-layer tablet comprising: (a) an immediate-release layer that comprises promethazine or a pharmaceutically acceptable salt thereof; and (b) a controlled-release layer that comprises an opioid analgesic agent and a non-opioid analgesic agent, wherein the non-opioid analgesic agent is acetaminophen or a pharmaceutically acceptable salt thereof, wherein the opioid analgesic agent is hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, wherein about 90% of the promethazine or a pharmaceutically acceptable salt thereof is released in about 1 minute to about 20 minutes following administration and about 100% of the promethazine or a pharmaceutically acceptable salt thereof is released within about 1 hour following administration, and wherein the hydrocodone, oxycodone, or a pharmaceutically acceptable salt thereof, is released within about 20 minutes to about 180 minutes following administration.
6. The bi-layer tablet of claim 1 , wherein the opioid analgesic agent is the hydrocodone or a pharmaceutically acceptable salt thereof.
7. The bi-layer tablet of claim 1 , wherein the opioid analgesic agent is the oxycodone or a pharmaceutically acceptable salt thereof.
8. The bi-layer tablet of claim 1 , comprising from 5 to 13 mg of the promethazine or a pharmaceutically acceptable salt thereof, from 310 to 330 mg of the acetaminophen or a pharmaceutically acceptable salt thereof, and from 6 to 8 mg of the hydrocodone or a pharmaceutically acceptable salt thereof.
9. The bi-layer tablet of claim 1 , comprising about 12.5 mg of the promethazine or a pharmaceutically acceptable salt thereof, about 325 mg of the acetaminophen or a pharmaceutically acceptable salt thereof, and about 7.5 mg of the hydrocodone or a pharmaceutically acceptable salt thereof.
10. The bi-layer tablet of claim 1 , comprising the promethazine or a pharmaceutically acceptable salt thereof, the acetaminophen or a pharmaceutically acceptable salt thereof, and the hydrocodone or a pharmaceutically acceptable salt thereof in a mass ratio of about (1 to 2):(40 to 45):(1 to 2).
11. The bi-layer tablet of claim 1 , comprising the promethazine or a pharmaceutically acceptable salt thereof, the acetaminophen or a pharmaceutically acceptable salt thereof, and the hydrocodone or a pharmaceutically acceptable salt thereof in a mass ratio of about (1.67):(43.33):(1).
12. The bi-layer tablet of claim 1 , further comprising an opioid antagonist or an additional agent for reducing abuse and/or diversion.
13. The bi-layer tablet of claim 12 , wherein the opioid antagonist is nalmefene, naloxone, or naltrexone.