Medication Management

Drug-Drug Interactions Focus of PBMs’ Efforts

New order-level systems could save $20 billion by preventing adverse events

Martin Sipkoff

Drug-drug interactions (DDIs) can make a medication less effective, cause unexpected and serious side effects, or inadvertently increase the action of a particular drug. Inadvertent DDIs occur more often when patients are receiving prescriptions from more than one physician at a time, or filling prescriptions at more than one pharmacy.

They account for almost 4 percent of all emergency room visits and about one-third of adverse drug events in hospitalized patients, according to Identifying and Preventing Medication Errors from the National Academies of Science (NAS). The Center for Information Technology Leadership estimates that the use of order-level technology could eliminate 2.1 million of the annual 3 million preventable adverse drug events, including DDIs, that occur in outpatient settings every year, saving more than $20 billion.

Prescription Solutions lists most prevalent DDIs

  1. Warfarin and enzyme inhibitors (to prevent clotting of blood in the body)
  2. Potassium-sparing diuretics and potassium supplements (to manage hypertension and/or certain heart conditions)
  3. Warfarin and NSAIDs (to prevent clotting of blood and to reduce pain or inflammation in the body)
  4. Simvastatin/lovastatin and some calcium channel blockers (to manage cholesterol levels and certain heart conditions)
  5. Simvastatin/lovastatin and CYP3A4 inhibitors (to manage cholesterol/medications that affect liver enzymes)
  6. Triptans and SSRIs/SNRIs (to relieve migraine headaches/to manage depression)

Pharmacy benefit management companies are aware of this potential for adverse drug events and take steps to reduce DDIs.

One successful technology was recently developed by Prescription Solutions, a PBM owned by UnitedHealth Group. Named the Drug Interaction Alert Program (DIAP), it quickly identifies potentially harmful DDIs. It is designed to target DDIs resulting from prescribing by at least two physicians. The program recently received a Best Practices in Consumer Empowerment and Protection Award from URAC, the accreditation organization.

“DDIs can be very costly and usually are preventable,” says Brian K. Solow, MD, a vice president and medical director for clinical services at Prescription Solutions. “Our program directly addresses the lack of coordinated care that can exist with patients under the care of multiple prescribers. What makes it unique, we believe, is that we always fax physicians on a daily basis after we receive batch reports from our member pharmacies. Most PBMs notify by letter, and most do so only on a weekly basis.”

An example of the kind of improved quality DIAP is designed to achieve is reduced risk for serious gastrointestinal bleeding — five times as high in patients exposed to a combination of warfarin and NSAIDs compared to patients taking warfarin alone. “Expanded over larger patient populations, this program could save health plans and employers millions of dollars a year,” says Solow. “The savings can be used for valuable health services, from disease prevention to the treatment of chronic illnesses.”

Prescription Solution’s emphasis on reducing DDIs “is because we grew out of a health plan which already stressed reducing adverse drug events,” says Solow. “That encouraged an extra push we believed would be especially effective. DIAP is a collaborative program with pharmacists and physicians that can find and stop interactions in real time, before they can be harmful to members.”

“We designed the program to include not only drugs that are overtly contraindicated,” adds Jennifer Shin, PharmD, Prescription Solutions’ manager of clinical programs, “but also drugs that our own literature review demonstrates should be avoided because of potentially negative DDIs.”

Real-time alerts

Most PBMs do provide real-time alerts to pharmacists when a prescription is being filled if the PBM’s software recognizes a potential DDI problem. But alerts can be overridden by pharmacists, who may assume that a prescribing physician is aware that a potential DDI exists but has made the prescribing decision believing no serious threat exists. Pharmacists may in fact fail to notify a physician of an on-screen alert for several reasons, including time restraints, says Solow. DIAP quickly notifies prescribing physicians, regardless of a pharmacist’s decision.

Prescription Solutions tested the effectiveness of DIAP. It helped to resolve potentially dangerous DDIs for 40 percent of 8,000 targeted plan members. “We tested the program against a control group,” says Solow. “Forty percent of the physicians responded by changing their prescriptions.”

An analysis of just one of the three most common interactions — potassium-sparing diuretics/potassium supplements — estimated that more than $13,000 was saved per avoidable adverse event, “highlighting the significant savings plan sponsors can achieve over larger patient populations,” says Shin.

For the 8,000 plan members who had interventions for the top three most prevalent drug-drug interactions, the program saved the plan sponsor an estimated $375,000, or $3.72 per member per month in medical costs, according to the PBM.

Medco, another of the nation’s largest PBMs, provides what it calls concurrent drug utilization review to all its clients. “CDUR provides real-time alerts that appear on the pharmacist’s screen as he or she processes the prescription,” says Terri Walker, RPh, senior director for “utilization management solutions.”

“These alerts identify potentially dangerous DDIs. For severe DDIs, the CDUR system requires the pharmacist to enter information indicating that he or she contacted the member’s physician and discussed this issue with the physician before the claim is adjudicated.” The program edits apply to all retail and mail order members. Medco’s clinicians review clinical information weekly and update the CDUR alerts as needed, says Walker.

In addition, a program Medco calls RationalMed integrates a patient’s medical, pharmacy, laboratory and self-reported data, scans patient populations and detects potential safety risks that could lead to DDI or other adverse drug events, says Walker. “The RationalMed system will send a fax, if a fax number for the physician is on file, or letter to the physician indicating the potentially serious drug-drug interaction. As with CDUR, Medco monitors clinical news weekly and updates RationalMed as needed.”

Variety of ratings systems

CVS Caremark has similar systems. “We have a variety of rating systems for drug interactions based on the severity of the interaction, whether they are major, moderate, minor, and the probability that an interaction will occur, either definite, probable, or suspected,” says spokeswoman Christine Cramer. “We utilize First Data Bank/MediSpan data and claims data ... to identify potential DDIs and will send a message to the dispensing pharmacy, either by mail or within the retail network, regarding major drug interactions regardless of probability.”

CVS Caremark also has additional drug interaction checks in its clinical programs. “Some interactions become more relevant the longer the patient is on the drug or with sustained use of concurrent medications,” says Cramer. In those cases, Caremark usually sends the prescriber a fax or letter.

“The idea is to create as much of a partnership with the physician as we possibly can,” says Prescription Solution’s Shin. “That in turn creates quality for our clients.”

“Traditional DDI programs only check for problems after a patient has been taking a medication,” says Brian K. Solow, MD, of Prescription Solutions.


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