Abuse liability studies can provide valuable information regarding the abuse potential of a drug in recreational drug users. Limiting abuse is particularly important with ER formulations, as they have an increase in total drug load that may increase the potential for abuse and the risk of overdose [ 24 ].
Abuse potential after oral administration was evaluated, as this route has been shown to be the most common route of administration in the abuse of hydrocodone products [ 16 , 17 ]. The outcomes for secondary measures were consistent with these results, showing that positive, negative, and sedative drug effects were diminished with intact and finely crushed hydrocodone ER tablet compared with hydrocodone IR.
Pupillometry assessments confirmed that the physiologic effects of intact or crushed hydrocodone ER were significantly lower compared with those of hydrocodone IR. Reductions in drug liking with ER formulations of opioids e. In a study by Webster et al evaluating the abuse potential of different formulations of oxycodone, drug liking was lower with the intact ER formulation of oxycodone than with IR oxycodone [ 25 ].
However, when the ER oxycodone tablet was crushed, drug-liking results resembled those seen with the IR oxycodone formulation [ 25 ]. Mean drug liking was significantly lower for both the intact and chewed ER drug compared with the hydrocodone IR solution. The present study used finely crushed tablets, which may provide a more rigorous standard for assessing abuse potential than chewing. However, given that intact hydrocodone ER behaves much like placebo, there was a significant increase in most drug likeability and effect measures when comparing crushed to intact hydrocodone ER, suggesting that potential for abuse cannot be fully eliminated.
The pharmacokinetic properties of hydrocodone IR and hydrocodone ER intact and crushed were consistent with the known profile of hydrocodone IR products and hydrocodone ER in earlier studies [ 18—21 ]. Overall systemic exposure to hydrocodone was comparable between the treatments. Although this study was conducted prior to the FDA issuing recommendations on assessment of opioid abuse-deterrent potential, the design is consistent with these guidelines [ 4 ], as well as with previous studies of drug liking and abuse potential [ 11 , 23 ].
A crossover design was employed to control for within-subject variability, and subjects were required to have a history of recreational drug abuse for eligibility. Additionally, a qualification phase was implemented to ensure the study did not enroll a substantial percentage of nonresponders patients not able to discriminate between active drug and placebo [ 26 , 29 ].
Results from this abuse potential study are in line with results from in vitro manipulation and extraction studies and pharmacokinetic studies of hydrocodone ER, and confirm the abuse-deterrent properties of this hydrocodone ER formulation which limits rapid release of drug when finely crushed, significantly reducing drug-liking compared with hydrocodone IR.
However, because these studies are typically conducted in controlled settings with small sample sizes, caution must be taken when generalizing these results to the at-risk population. A number of additional factors also may play an important role in the abuse of an opioid in the real-world setting, including cost, accessibility, mechanisms of abuse, and what other peers are abusing. As such, the FDA recommends phase IV, post-marketing studies to assess the abuse potential of a product in the community [ 4 ].
In this study, hydrocodone ER, orally administered intact or finely crushed, and hydrocodone IR were generally well tolerated in the healthy nondependent recreational opioid users. No new safety issues associated with the use of hydrocodone ER were observed. Positive, negative, and sedative drug effects were also diminished with intact and finely crushed hydrocodone ER tablet compared with hydrocodone IR. When administered as intended intact orally , liking scores for hydrocodone ER were similar to those for placebo.
Additionally, assessment of pharmacokinetic parameters for the finely crushed hydrocodone ER tablet showed that it retained some of its ER properties. The reduced dosing frequency and lower abuse potential of this hydrocodone ER tablet may provide a much needed alternative to currently available, combination hydrocodone IR products. Funding sources: Medical writing assistance was provided by Bina J. Frazer, PA. Teva provided a full review of the article.
The study was sponsored by Cephalon, Inc. Trial registration: ClinicalTrials. National Center for Biotechnology Information , U. Pain Med. Published online Jan Webster , MD. Lynn R. Author information Copyright and License information Disclaimer. Corresponding author. Tel: ; Fax: ; E-mail: moc. For commercial re-use, please contact journals.
This article has been cited by other articles in PMC. Abstract Objective. Introduction Recreational use of prescription pain relievers has become more prevalent in the United States than use of cocaine, heroin, and methamphetamine combined [ 1 ]. Methods This randomized, double-blind, triple-dummy, placebo-controlled, crossover study was conducted at one study site in the United States between January and May in accordance with the Good Clinical Practice: Consolidated Guideline approved by the International Conference on Harmonisation and applicable national and local laws and regulations [ 22 ].
Subjects The study enrolled men and women age 18 to 50 years who were not physically dependent on opioids as shown by successful completion of a naloxone challenge i. Study Design After completing screening procedures, eligible subjects participated in a qualification phase to ensure they could tolerate a mg dose of hydrocodone IR and could discriminate between the effects of hydrocodone and placebo.
Pharmacodynamic Assessments The questionnaires and pharmacodynamic measures used to evaluate subjective abuse potential are summarized in Table 1. Table 1 Questionnaires used to assess subjective drug effects. Open in a separate window. Safety Safety and tolerability were assessed by monitoring adverse events AEs , clinical laboratory test results, vital sign measurements, ECG and physical examination findings, oxyhemoglobin saturation SpO 2 measurements, and concomitant medication use.
Results Subjects Of the subjects screened, were enrolled into the qualification phase and 49 were randomized into the treatment phase, received at least one dose of study drug, and were evaluable for safety Figure 1. Figure 1. Subject disposition. Figure 2. Figure 3. Table 2 Mean SD scores on secondary pharmacodynamic measures of subjective drug effects by treatment. Figure 4. Figure 5.
Figure 6. Figure 7. Table 3 Mean SD pharmacokinetic parameters for hydrocodone by treatment. Safety and Tolerability Subjects enrolled in this study were nondependent, recreational opioid users. Discussion Abuse liability studies can provide valuable information regarding the abuse potential of a drug in recreational drug users. References 1. SMA Centers for Disease Control and Prevention. Emergency department visits involving nonmedical use of selected prescription drugs—United States, — Vital signs: Overdoses of prescription opioid pain relievers—United States, — US Food and Drug Administration.
If your dose is different, do not change it unless your doctor tells you to do so. The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. If you miss a dose of this medicine, take it as soon as possible.
However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses. Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Hydrocodone can cause serious unwanted effects or fatal overdose if taken by children, pets, or adults who are not used to strong narcotic pain medicines.
Make sure you store the medicine in a safe and secure place to prevent others from getting it. Drop off any unused narcotic medicine at a drug take-back location right away. If you do not have a drug take-back location near you, flush any unused narcotic medicine down the toilet. Check your local drug store and clinics for take-back locations.
You can also check the DEA web site for locations. Here is the link to the FDA safe disposal of medicines website: www. There is a problem with information submitted for this request. Sign up for free, and stay up-to-date on research advancements, health tips and current health topics, like COVID, plus expert advice on managing your health.
Error Email field is required. Carefully check the labels of all other medicines you are using, because they may also contain acetaminophen. It is not safe to use more than 4 grams 4, milligrams of acetaminophen in one day 24 hours.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so. The amount of medicine that you take depends on the strength of the medicine.
Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses. Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Hydrocodone can cause serious unwanted effects or fatal overdose if taken by children, pets, or adults who are not used to strong narcotic pain medicines.
Make sure you store the medicine in a safe and secure place to prevent others from getting it. Drop off any unused narcotic medicine at a drug take-back location right away. If you do not have a drug take-back location near you, flush any unused narcotic medicine down the toilet.
Check your local drug store and clinics for take-back locations. You can also check the DEA web site for locations. Here is the link to the FDA safe disposal of medicines website: www. It is very important that your doctor check your or your child's progress while using this medicine, especially within the first 24 to 72 hours of treatment.
This will allow your doctor to see if the medicine is working properly and to decide if you or your child should continue to take it. Blood and urine tests may be needed to check for unwanted effects. It is against the law and dangerous for anyone else to use your medicine. Keep your unused tablets in a safe and secure place. People who are addicted to drugs might want to steal this medicine.
This medicine will add to the effects of alcohol and other CNS depressants medicines that can make you drowsy or less alert. Some examples of CNS depressants are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics numbing medicines , including some dental anesthetics.
Also, there may be a greater risk of liver damage if you drink three or more alcoholic beverages while you are taking acetaminophen. Do not drink alcoholic beverages, and check with your doctor before taking any of these medicines while you are using this medicine. This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose.
If you think you or someone else may have taken an overdose of this medicine, get emergency help at once. Your doctor may also give naloxone to treat an overdose. Signs of an overdose include: cold, clammy skin, coughing that sometimes produces a pink frothy sputum, dark urine, difficult or trouble breathing, irregular, fast or slow, or shallow breathing, nausea, vomiting, pain in the upper stomach, pale or blue lips, fingernails, or skin, pinpoint pupils of the eyes, or yellow eyes or skin.
This medicine may cause sleep-related breathing problems eg, sleep apnea, sleep-related hypoxemia. Your doctor may decrease your dose if you have sleep apnea stop breathing for short periods during sleep while using this medicine.
This medicine may cause adrenal gland problems. Check with your doctor right away if you have darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting. Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin.
These could be symptoms of a serious liver problem. This medicine may cause serious skin reactions eg, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, chills, cough, diarrhea, itching, joint or muscle pain, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, or unusual tiredness or weakness.
This medicine may cause a serious type of allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.
Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem.
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