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Knowing Opioid Medication Formulations and Eliminating Confusion
Knowing Opioid Medication Formulations and Eliminating Confusion Opioid medications are also known as narcotics and are often used for pain management. They work by binding to opioid receptors and are highly addictive, which may produce feelings of euphoria, warmth, and relaxation.1 Common side effects associated with opioids involve the central nervous system including sedation, respiratory depression, and mental confusion; the gastrointestinal system including nausea, vomiting, and constipation; and other side effects related to physical dependence and tolerance.2 Prolonged exposure to opioids will lead to opioid abuse and withdrawal symptoms upon discontinuation. According to the Centers for Disease Control and Prevention, 3 of 4 prescription drug overdoses are caused by inappropriate opioid use. Drug overdoses also contribute to high mortality rates. The current death rates associated with opioid overdose have more than tripled compared with the data in 1990.2 Opioid misuse is widespread and represents serious problems for health care practitioners. There are multiple means to abuse opioids, and they may include overingesting pills or capsules, chewing or crushing the tablets into powder for snorting, dissolving content for injection, and altering the integrity of the pill or its purpose for illicit use. Several commercial opioid medications are formulated in “abuse-deterrent” dosage forms to prevent misusage. The Table lists some of these newer
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products that are available. However, many of these products are not proven to decrease abuse. In fact, they may redirect abusers to other opioids or heroin. The costs of these new formulations are generally higher than traditional opioids. One should note that potential overdose
PRESCRIPTION PAD Timothy Nguyen, PharmD, BCPS is possible if the integrity of these formulations is altered. As always, advise patients to avoid alcohol while taking opioid medications. A Risk Evaluation and Mitigation Strategy (REMS) was implemented and aimed to reduce the misuse of long-acting opioids.3 There are a number of opioids that are required under the REMS program. The REMS program offers training to prescribers and educational materials to patients as needed. It is important for health care practitioners to educate the public about the overdose risks and use reversal medication naloxone when needed.
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Table. Selected Opioid Formulations and Related Medications4,5 Ingredients Buprenorphine and naloxone
New Brand Name Bunavail (BioDelivery Sciences, Raleigh, NC)
Comments
Other familiar names: Suboxone For maintenance treatment of opioid dependence Buccal film (CIII) Has a unique adhesive “inside the cheek” delivery system Improves absorption & plasma concentrations of buprenorphine Can be delivered at a lower dose, which may help reduce the potential for misuse and diversion & lessens the incidence of side effects
Zubsolv (Orexo Formulated so that it blocks some of the “high” if crushed for US, New York, NY) snorted or injected. Fentanyl
Lazanda (Depomed Other familiar names: Actiq, Duragesic, Fentanyl, Fentora, Inc., Newark, CA) Abstral Nasal spray formulation Absorbed a little faster than fentanyl lozenge but has a similar onset for pain relief Not equivalent with other products so do not substitute
Hydrocodone
Zohydro ER (Zogenix Inc., Ireland)
Other familiar names: Vicodine, Lortab, Norco (these products contains APAP) LA formulation, designed “abuse-deterrent” but many argue it is not Contains w10 times more than Vicodine The only ER hydrocodone dosage form available without APAP (this eliminates concern APAP liver toxicity) Creation of a prodrug that does not exert a significant analgesic effect until it has been metabolized within the GI tract
Hydromorphone
Exalgo (Mallinckrodt Pharm., Hazelwood, MO)
Other familiar names: Dilaudid ER formulation Once daily dosing Very potent opioids
Palladone (Purdue ER hydromorphone Off the market because alcohol caused the drug to release Pharma. L.P., too fast Stamford, CT) Oxycodone
OxyContin (Purdue Other familiar names: Roxicodone, Percocet (also contains APAP), Percodan (also contains ASA), others available in Pharma. L.P., combination with ibuprofen Stamford, CT) ER, reformulated with tamper-resistant Harder to cut or chew Break into clumps if crushed or turn into a thick gel so can’t snorted or injected OxyContin “OP”
“OP” are hard to crush or chew
Oxecta (Pfizer Inc., Tamper-resistant New York, NY) IR oxycodone formulated to discourage crush, chew, snort, or inject, it breaks into chunks instead of powder, also contains sodium laurel sulfate which irritates the nose if snorted, caution not to use in feeding tubes, it can clog the line. Aversion techniques involving incorporation of substances that will result in unpleasant side effects if higher dose is ingested or dosage form is manipulated prior to ingestion continued 866
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Volume 10, Issue 10, November/December 2014
Table. (continued ) Ingredients
New Brand Name
Comments
Targiniq ER (Purdue FDA approved abuse-deterrent ER formulation of oxycodone & naloxone Pharma. L.P., Naloxone helps blocked the euphoric effects of oxycodone Stamford, CT) For severe pain daily around-the-clock dosing Oxycodone/ acetaminophen
Xartemis XR (Mallinckrodt Pharm., Hazelwood, MO)
Morphine and naltrexone
Embeda (Pfizer Inc., ER morphine pellets with naltrexone inner core New York, NY) Designed to limit abuse, however, may not work properly if crushed Creating a dosage form containing an opioid antagonist that will diminish the sense of euphoria experienced
Tapentadol
Some trials suggest that tapentadol may cause less GI side Nucynta ER effects in comparison with oxycodone or morphine (Janssen Pharm Inc., Titusville, NJ) A physical barrier that renders it impossible to chew, crush, or grind tablets
Other familiar names: Percocet Formulation includes biphasic IR and ER delivery of both oxycodone and APAP (OC/APAP ER). This allows for pain relief as quickly as within an hour while providing a long-lasting effect for several hours. Dosing is twice-daily. Advantages over IR OC/APAP formulation are: Improved adherence, decreased frequency of dosing & lessened pill burden Better control of breakthrough pain Improved quality of sleep due to less episodes of being awoken by pain & needing to take an additional dose during the night
Mu-opioid receptor antagonist Naloxone HCl
Evzio (Kaleo Inc., Richmond, VA)
Other familiar names: Narcan Mu-opioid receptor antagonist Handheld autoinjector device Subcutaneous or IM for opioid overdose
APAP ¼ acetaminophen; ASA ¼ aspirin; ER ¼ extended release; GI ¼ gastrointestinal; IM ¼ intramuscular; IR ¼ immediate release; LA ¼ long-acting.
References 1. Prescription Drug Abuse. http://www.drugabuse.gov/publications/ research-reports/prescription-drugs/opioids/what-are-opioids. Accessed April 16, 2014. 2. Policy Impact: prescription painkiller overdoses. CDC and prevention. http://www.cdc.gov/homeandrecreationalsafety/rxbrief. Accessed April 16, 2014. 3. http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ ucm163647.htm. Accessed July 18, 2014. 4. Lexi-Drugs online [Internet]. Hudson, OH: Lexi-Comp, Inc; 1978-2010. http://online.lexi.com. Accessed July 18, 2014. 5. Miromedex healthcare series. DRUGDEX system. Greenwood Village, CO: Truven Health Analytics; 2013. http://www.thomsonhc.com. Accessed July 18, 2014.
www.npjournal.org
Timothy Nguyen, PharmD, BCPS, CCP, FASCP is an Associate Professor at LIU Pharmacy (The Arnold & Marie Schwartz College of Pharmacy and Health Sciences), New York and Adjunct Clinical Pharmacology Professor, LIU’s Division of Physician Assistant Studies and Saint Peter’s University (Master of Science in Nursing). He can be reached at [email protected].
1555-4155/14/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2014.07.039
The Journal for Nurse Practitioners - JNP
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www.npjournal.org
products that are available. However, many of these products are not proven to decrease abuse. In fact, they may redirect abusers to other opioids or heroin. The costs of these new formulations are generally higher than traditional opioids. One should note that potential overdose
PRESCRIPTION PAD Timothy Nguyen, PharmD, BCPS is possible if the integrity of these formulations is altered. As always, advise patients to avoid alcohol while taking opioid medications. A Risk Evaluation and Mitigation Strategy (REMS) was implemented and aimed to reduce the misuse of long-acting opioids.3 There are a number of opioids that are required under the REMS program. The REMS program offers training to prescribers and educational materials to patients as needed. It is important for health care practitioners to educate the public about the overdose risks and use reversal medication naloxone when needed.
The Journal for Nurse Practitioners - JNP
865
JNP
Table. Selected Opioid Formulations and Related Medications4,5 Ingredients Buprenorphine and naloxone
New Brand Name Bunavail (BioDelivery Sciences, Raleigh, NC)
Comments
Other familiar names: Suboxone For maintenance treatment of opioid dependence Buccal film (CIII) Has a unique adhesive “inside the cheek” delivery system Improves absorption & plasma concentrations of buprenorphine Can be delivered at a lower dose, which may help reduce the potential for misuse and diversion & lessens the incidence of side effects
Zubsolv (Orexo Formulated so that it blocks some of the “high” if crushed for US, New York, NY) snorted or injected. Fentanyl
Lazanda (Depomed Other familiar names: Actiq, Duragesic, Fentanyl, Fentora, Inc., Newark, CA) Abstral Nasal spray formulation Absorbed a little faster than fentanyl lozenge but has a similar onset for pain relief Not equivalent with other products so do not substitute
Hydrocodone
Zohydro ER (Zogenix Inc., Ireland)
Other familiar names: Vicodine, Lortab, Norco (these products contains APAP) LA formulation, designed “abuse-deterrent” but many argue it is not Contains w10 times more than Vicodine The only ER hydrocodone dosage form available without APAP (this eliminates concern APAP liver toxicity) Creation of a prodrug that does not exert a significant analgesic effect until it has been metabolized within the GI tract
Hydromorphone
Exalgo (Mallinckrodt Pharm., Hazelwood, MO)
Other familiar names: Dilaudid ER formulation Once daily dosing Very potent opioids
Palladone (Purdue ER hydromorphone Off the market because alcohol caused the drug to release Pharma. L.P., too fast Stamford, CT) Oxycodone
OxyContin (Purdue Other familiar names: Roxicodone, Percocet (also contains APAP), Percodan (also contains ASA), others available in Pharma. L.P., combination with ibuprofen Stamford, CT) ER, reformulated with tamper-resistant Harder to cut or chew Break into clumps if crushed or turn into a thick gel so can’t snorted or injected OxyContin “OP”
“OP” are hard to crush or chew
Oxecta (Pfizer Inc., Tamper-resistant New York, NY) IR oxycodone formulated to discourage crush, chew, snort, or inject, it breaks into chunks instead of powder, also contains sodium laurel sulfate which irritates the nose if snorted, caution not to use in feeding tubes, it can clog the line. Aversion techniques involving incorporation of substances that will result in unpleasant side effects if higher dose is ingested or dosage form is manipulated prior to ingestion continued 866
The Journal for Nurse Practitioners - JNP
Volume 10, Issue 10, November/December 2014
Table. (continued ) Ingredients
New Brand Name
Comments
Targiniq ER (Purdue FDA approved abuse-deterrent ER formulation of oxycodone & naloxone Pharma. L.P., Naloxone helps blocked the euphoric effects of oxycodone Stamford, CT) For severe pain daily around-the-clock dosing Oxycodone/ acetaminophen
Xartemis XR (Mallinckrodt Pharm., Hazelwood, MO)
Morphine and naltrexone
Embeda (Pfizer Inc., ER morphine pellets with naltrexone inner core New York, NY) Designed to limit abuse, however, may not work properly if crushed Creating a dosage form containing an opioid antagonist that will diminish the sense of euphoria experienced
Tapentadol
Some trials suggest that tapentadol may cause less GI side Nucynta ER effects in comparison with oxycodone or morphine (Janssen Pharm Inc., Titusville, NJ) A physical barrier that renders it impossible to chew, crush, or grind tablets
Other familiar names: Percocet Formulation includes biphasic IR and ER delivery of both oxycodone and APAP (OC/APAP ER). This allows for pain relief as quickly as within an hour while providing a long-lasting effect for several hours. Dosing is twice-daily. Advantages over IR OC/APAP formulation are: Improved adherence, decreased frequency of dosing & lessened pill burden Better control of breakthrough pain Improved quality of sleep due to less episodes of being awoken by pain & needing to take an additional dose during the night
Mu-opioid receptor antagonist Naloxone HCl
Evzio (Kaleo Inc., Richmond, VA)
Other familiar names: Narcan Mu-opioid receptor antagonist Handheld autoinjector device Subcutaneous or IM for opioid overdose
APAP ¼ acetaminophen; ASA ¼ aspirin; ER ¼ extended release; GI ¼ gastrointestinal; IM ¼ intramuscular; IR ¼ immediate release; LA ¼ long-acting.
References 1. Prescription Drug Abuse. http://www.drugabuse.gov/publications/ research-reports/prescription-drugs/opioids/what-are-opioids. Accessed April 16, 2014. 2. Policy Impact: prescription painkiller overdoses. CDC and prevention. http://www.cdc.gov/homeandrecreationalsafety/rxbrief. Accessed April 16, 2014. 3. http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ ucm163647.htm. Accessed July 18, 2014. 4. Lexi-Drugs online [Internet]. Hudson, OH: Lexi-Comp, Inc; 1978-2010. http://online.lexi.com. Accessed July 18, 2014. 5. Miromedex healthcare series. DRUGDEX system. Greenwood Village, CO: Truven Health Analytics; 2013. http://www.thomsonhc.com. Accessed July 18, 2014.
www.npjournal.org
Timothy Nguyen, PharmD, BCPS, CCP, FASCP is an Associate Professor at LIU Pharmacy (The Arnold & Marie Schwartz College of Pharmacy and Health Sciences), New York and Adjunct Clinical Pharmacology Professor, LIU’s Division of Physician Assistant Studies and Saint Peter’s University (Master of Science in Nursing). He can be reached at [email protected].
1555-4155/14/$ see front matter © 2014 Elsevier, Inc. All rights reserved. http://dx.doi.org/10.1016/j.nurpra.2014.07.039
The Journal for Nurse Practitioners - JNP
867