Economic impact of potential drug-drug interactions among osteoarthritis patients taking opioids.

Patients with osteoarthritis (OA) taking at least one CYP450-metabolized opioid concurrently with another CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk of a pharmacokinetic drug-drug interaction (PK DDI). This study compared patients with and without such an incident DDE to determine healthcare utilization and associated payments. Using a retrospective database analysis, the impact of DDEs was evaluated in terms of associated clinical events, healthcare services utilization (office visits, outpatient visits, ED visits, hospitalization), and payments in patient populations based on age (those under age 65 and those 65 years of age and older), during the 6 months after exposure. DDE patients had significantly more inpatient hospitalizations than no-DDE patients. Mean total payments at 6 months were significantly higher for both younger and older patients with DDE compared to similar patients without DDE ($9,469, SD = $12,192 vs. $8,382, SD = $14,078, respectively, for younger patients, resulting in a difference of $1,087, P < 0.004, and $9,829, SD = $11,721 vs. $8,622, SD = $10,131, respectively, for older patients, resulting in a difference of $1,207, P = 0.001). In both age groups, DDE patients had significantly higher payments for nonopioid prescription drugs ($1,824 SD = $2,420 vs. $1,362, SD = $1,891, respectively, for younger patients, resulting in a difference of $462, P < 0.001, and $2,197 SD = $2,332 vs. $2,013, SD = $2,437, respectively, for older patients, resulting in a difference of $184, P = 0.020). Overall, patients with OA who experienced DDEs had significantly greater utilization rates of healthcare resources and higher associated payments in the 6-month observation period following the exposure, compared to patients without DDEs, consistent with the risk of PK DDIs associated with DDEs.

Economic impact of potential CYP450 pharmacokinetic drug-drug interactions among chronic low back pain patients taking opioids.

Chronic low back pain (cLBP) patients who take at least 1 CYP450-metabolized opioid analgesic agent concurrent with at least 1 other CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk for a pharmacokinetic drug-drug interaction (PK DDI). This study compared utilization of healthcare resources and associated payments in cLBP patients with and without incident DDEs with the potential to cause PK DDIs. A retrospective database analysis examined the associated clinical events, healthcare utilization (measured in terms of claims for office visits, outpatient visits, emergency department visits, and hospitalization), and cost to the health plan, as defined as the sum of health plan payments for resources used. Patients were grouped into 2 cohorts by age (those under 65 and those 65 years and over). In the 6 months after exposure, total healthcare payments were significantly higher for DDE patients than those without DDEs (no-DDE), in both in the younger ($7,086, SD = $8,370) and $6,353, SD = $8,352, respectively, P < 0.001) and the older cohorts ($7,806 vs. $7,043, respectively, P = 0.013). Younger and older patients with DDE had significantly higher prescription payments than those without DDE ($2,041, SD = $2,706 vs. $1,565, SD = $2,349, respectively, P < 0.001 for younger and $2,482, SD = $2,481 vs. $2,286, SD = $2,521, respectively, P = 0.044 for older patients). Both older and younger patients with DDE had significantly more claims for office visits and higher associated payments than similar patients without DDE. Patients in the study who experienced DDEs that placed them at risk for PK DDIs had significantly greater utilization rates of healthcare resources and higher associated payments in the 6-month observation period following exposure.

Continuous multimechanistic postoperative analgesia: a rationale for transitioning from intravenous acetaminophen and opioids to oral formulations.

Good surgical outcomes depend in part on good pain relief, allowing for early mobilization, optimal recovery, and patient satisfaction. Postsurgical pain has multiple mechanisms, and multimechanistic approaches to postoperative analgesia are recommended and may be associated with improved pain relief, lowered opioid doses, and sometimes a lower rate of opioid-associated side effects. Acetaminophen (paracetamol) is a familiar agent for treating many types of pain, including postsurgical pain. Oral acetaminophen has been shown to be safe and effective in a variety of acute pain models. Combination products using a fixed-dose of acetaminophen and an opioid have also been effective in treating postsurgical pain. Combination products with acetaminophen have demonstrated an opioid-sparing effect, which inconsistently results in a reduced rate of opioid-associated side effects. Intravenous (IV) acetaminophen and an opioid analgesic administered in the perioperative period may be followed by an oral acetaminophen and opioid combination in the postoperative period. Transitioning from an IV acetaminophen and opioid formulation to a similar but oral formulation of the same drugs appears to be a reasonable step in that both analgesic therapies are known to be safe and effective. For postsurgical analgesia with any acetaminophen product, patient education is necessary to be sure that the patient does not concurrently take any over-the-counter products containing acetaminophen and accidentally exceed dose limits.

Exposure to potential CYP450 pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions.

Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug-drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug-drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P < 0.05). This study challenged previous assumptions about DDEs in that advanced age was not positively associated with the risk of DDE. However, the number of prescriptions the patient received in the 90-day window prior to the index date was a risk factor. For patients taking at least two medications in the 90-day period prior to the index date, every additional prescription taken increased their risk for a DDE during the observation period by 138% (on average). The risk of DDE during the study period was threefold greater for patients with one medication in the 90-day period before index date compared with similar patients with no prescriptions in that same period before the index date. DDEs are more common than may be generally believed in patients with osteoarthritis, regardless of age, and can occur even in patients taking few medications. When selecting an opioid analgesic to treat osteoarthritis, physicians should consider the potential for exposure of these patients to drugs that could interact unfavorably.

Prevalence of exposure to potential CYP450 pharmacokinetic drug-drug interactions among patients with chronic low back pain taking opioids.

Drug-drug interactions (DDIs) have been defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system, including some, but not all, opioids experience a drug-drug exposure (DDE), which may result in a potentially dangerous DDI. Using a retrospective analysis of a large commercial claims database and a Medicare database, we evaluated DDEs that have the potential to cause DDIs among chronic low back pain (cLBP) patients on long-term opioid analgesia, which metabolizes through the CYP450 enzyme system, concomitant with other CYP450-metabolized drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56 to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively), followed by patients 34 to 45 years (27.9%). For patients>65 years, the prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly consistent across age ranges in this population. This study suggests that DDEs are common in the cLBP population. When selecting an opioid to treat cLBP, physicians should consider the potential for exposure of these patients to drugs that might unfavorably interact and, for that reason, the use of opioids that do not rely on the CYP450 system as their primary means of metabolism might be worthy of consideration.