WARFARIN & SULFONAMIDES This interaction is one of the most well supported in the literature. The scenario is that a patient presents with signs and symptoms of UTI and the drug of choice appears to be Septra or Bactrim DS (sulfamethoxazole / trimethoprim). However, the sulfa antibiotic is known to displace warfarin from protein binding sites where more than 90% of warfarin is bound, affecting the clotting cascade. It is recommended to use an alternative antibiotic, or test INR soon after the sulfa antibiotic is started. The question then comes as to when to test. We recently experienced that scenario where the INR was tested 4 days after the start of the sulfa antibiotic, and there was a slight dose adjustment downward of the warfarin based on a higher, but not remarkably higher, INR. Several days later the INR was 7.7. The moral of the story: alternative drug therapy may be the safest approach.

WARFARIN & AMIODARONE Warfarin can also interact with amiodarone, (a serious interaction), so when starting amiodarone on someone receiving warfarin, frequent INR monitoring is warranted.

LITERATURE REVIEW An excellent review by Juurlink, DN and Redelmeier, DA, et al in 2003, studied hospital admissions likely due to drug interactions. Most  significant were:

• Those admitted for severe hypoglycemia and taking glyburide were 6 times more likely to have been started on a sulfa antibiotic in the last 7 days.

• Those admitted with digoxin toxicity were 12 times more likely to have been treated with clarithromycin (similar to azithromycin) in the previous week.

• Those admitted for hyperkalemia and treated with an ACE inhibitor were 20 times more likely to have been treated with spironolactone or other potassium-sparing diuretic in the previous week.

The above three suggest either alternative drug therapies, or frequent monitoring with patient education as to what symptoms to look for.

NSAIDs & SSRIs We know that NSAIDs are associated with increased risk of GI bleeding, with odds ratios from 1.5 to about 7.0, depending upon the drug. SSRI’s are also associated with a modest increase in risk for GI bleeding (odds ratio of 1.5-3.0). Of particular concern is that the combination of any NSAID with an SSRI results in a significantly elevated, disproportionate risk for GI bleeding with odds ratios as high as 15.6. The increase in risk is even seen with low-dose aspirin (odds ratio of 7.2).

With upper GI bleeding being a serious ADE leading to harm and hospitalization in older adults, this warrants a review of such combination therapy. It also begs the question, should we be using NSAIDs on a routine basis in older adults?

According to the American Geriatric Association (AGS) Pain Management Guidelines from 2009, chronic use of NSAIDs should be avoided in the older adult population whenever possible. If use is required, then mitigation of that risk, in part, should occur with the use of a proton pump inhibitor.

OTHER INTERACTIONS

• ACE inhibitors plus sulfonamides leading to hyperkalemia

• Warfarin and NSAIDs causing bleeding

• Warfarin and dicloxacillin leading to DECREASED INR

• ACEs or ARBs plus potassium supplements causing hyperkalemia

• Trimethoprim can increase serum digoxin levels by up to 75%

• Opiates (primarily Oxycontin or oxycodone) and SSRIs (Prozac, Zoloft, Lexapro, Celexa, etc) or SNRIs (Effexor) resulting in serotonin syndrome, may be more likely in older adults. Look for this in short-term rehab patients who start on relatively high doses of opiates to control pain from joint replacement surgery.

In closing, you now have a list of some of the most significant drug interactions that lead to ADEs in older adults. However, there are many that are not listed here which can be equally impacting to the lives of older adults. My recommendation is to use a drug interaction screening tool at the point-of-prescribing, or ensure that you encourage your patient to ask the pharmacist to ensure they have checked for all possible interactions. ADE avoidance is the best approach to safety.

Here is a summary of the report findings:

• Many studies used highly selected populations with high-severity of symptoms thereby there is lacking good evidence in those with mild to moderate symptoms.
• “As needed” drug therapies were not evaluated yet there is suggestion that “as needed” use may be beneficial and warrants further study.
• Secondary causes of RLS, such as iron deficiency, when corrected lead to symptom reduction.
• Non-drug treatments, such as exercise and compression stockings, are effective yet adherence to these methods is poor.
• Dopamine agonists,  such as Requip (ropinorole) and Mirapex (pramapexole), are effective at reducing symptoms but in many studies there was also a high placebo effect.
• Drop out rates from studies were high due to 1) augmentation (worsening of the disease symptoms from drug therapy) 7-62%, 2) adverse effects such as nausea, vomiting, somnolence, fatigue and 3) lack of effectiveness 6-32%.
• Benefits from medication therapies tended to not be sustained over time.
• GABA analogues, e.g. Neurontin (gabapentin) and Lyrica (pregabalin) showed no good evidence for efficacy.

One other consideration is to watch out for the adverse effects of orthostatic hypotension (dizziness upon standing) obsessive compulsive behaviors, gambling addictions, inappropriate sexual behaviors, and “sleep attacks” as uncommon but potentially life-altering adverse effects from dopamine therapies.

Tips:

• Maximize trials of non-drug options, such as stretching every day and before bedtime, improving sleep hygiene, and avoiding caffeine, nicotine, sedative hypnotics and antihistamines, all known to worsen RLS.
• If symptoms worsen after initiating drug therapies, consider that augmentation may be occurring and dose reduction may be appropriate, along with non-drug interventions.
• If any of the above symptoms appear after initiation of drug therapy, assume a drug is responsible.

However, the problem is that studies that seek to find ways to improve adherence do not equally as well study the probable increase in ADEs in their study population. This is evidenced in the AHRQ analysis on medication adherence solutions. Only three studies looked at ADEs as a possible negative outcome with none documented, but there was lacking homogeneity to conclude anything, most likely because they were not looking in great enough detail with the right screening tools. Not unlike why so many studies don’t match up on ADEs in older adults: “You see what you look for and recognize only what you know”. i.e. If you have a shallow knowledge base and don’t know how to recognize probable ADEs in older adults, you will not find them. What leads me to believe that specific research needs to be done is having searched the literature and finding that in the HIV/AIDS population there is good evidence that increasing adherence increases the incidence of ADEs. Since adherence is so critical in being successful at managing HIV/AIDS, they look at this closely, where as other studies do a cursory review.  So why wouldn’t that apply to other populations? Other drugs are toxic and other populations are not immune from ADEs.

But if you know that improving adherence in older adults can increase the risk for ADEs, then on a case-by-case basis you proceed with caution and monitor closely with the intent of improving adherence to achieve specific, realistic goals, but monitor for the development of ADEs. We not uncommonly find that people become dizzy from blood pressure medications after starting an adherence program, so we adjust doses downward. It then lends wisdom that a practitioner may consider lowering doses before starting an adherence program if there is documented poor adherence. Adhering to a well-designed drug regimen is probably one of the most effective forms of health care, when properly implemented.

I can recall how my balance improved remarkably while doing tai chi, and as I notice the declining changes in my balance since I’ve stopped, I think it’s a good time to start up again.  Remember: “Behaviors in mid-life are excellent predictors of success in late-life. “

http://www.effectivehealthcare.ahrq.gov/ehc/products/169/1030/ui_cons_fin_to_post.pdf

The authors then categorize patients based on how they make health care decisions, such as “minimalists”, who believe “less is more” (that’s me!), and “believers”, who believe there is a cure for everything, and then the “doubters”, “who worry that almost any treatment will be worse than the disease”. Then comes the categorization of “experts” being fitted into these categories, such as “the Federal Preventive Services Task force as “minimalists” and “doubters”, and that is why experts can look at the data and have differing opinions. The authors then make their point about the uncertainty of “best-evidence” saying, “No one can say with certainty who will benefit by taking a certain drug and who will not”.

Then there is the discussion about the delivery model of health care and how it’s changed. “Medical care used to be paternalism: A doctor dictated what was to be done and the patient complied. This model has largely been abandoned, but Democrats and Republicans are offering a new form of paternalism.”  I agree with the authors when they say treatement decisions should be made between doctor and patient, since everyone has differing circumstances with which they are confronted, and differing needs which alters their priorities, and a “cookie-cutter” style approach doesn’t always meet the needs of the person. However, something must be done to lower health care costs since we spend the most in the U.S., but don’t get the most in return, so I see clearly that certain restrictions and guidelines need to be applied in order to sustain health care services to all. We just need to determine what is the absolute “best-evidence” to start applying and measure the benefits of its application.

I responded to the question a few years back when someone asked me what I do and I said, “My job is to get as close to  the truth as is possible”, and that is what I have been doing for several years, gathering evidence, analyzing it, and determining when “evidence” is not the “best-evidence”, and sometimes downright false, and what evidence is, without a doubt, solid. What I have come to know to be true is that we are causing harm by misusing medications in older adults, to the degree that adverse drug events is now the 4th or 5th leading cause of death by disease and forecast to race to the top of the charts within 10 years. It is also clear that application of the “best-evidence” regarding the appropriate use of medications in older adults can prevent the majority of them from occurring, and lower costs by lowering health care utilization and avoiding complications. We just need to find a way to collaborate as health care providers, with the person at the center, and try to keep the best-evidence in front of us.

Here is the link to the WSJ article.

http://online.wsj.com/article/SB10001424052702303404704577311641531125820.html

In brief, this means that prior to cataract surgery an evaluation of whether surgery is appropriate in those who have used tamsulosin should occur, due to the fact the authors had little confidence in recommending discontinuing tamsulosin as an effective intervention strategy. The authors speculate that the drug-procedure interaction may exist because of the highly specific receptor binding of tamsulosin that is not seen with other alpha-blockers leading to relaxation of the smooth muscle responsible for iris dilation. This leads to unopposed muscle constriction resulting in intraoperative floppy iris syndrome (IFIS). The authors do list their study limitations, but regardless, this one is worth being aware of as a very possible serious adverse event risk.

Here’s the link: http://jama.ama-assn.org/content/301/19/1991.full

http://www.effectivehealthcare.ahrq.gov/ehc/products/160/1007/CER53_LowBoneDensity_FinalReport_20120329.pdf

http://www.fda.gov/Drugs/ResourcesForYou/SpecialFeatures/ucm297764.htm?source=govdelivery

The care coordination role involves coordinating community resources, referrals for additional care, and communicating with the PCP and other providers. This is an excellent use of the highly skilled pharmacist who has a vast amount of clinical knowledge, and it also demonstrates where pharmacists can expand their non-traditional roles by adding value to the health care system. The article is available to ASCP members only. Correspondence to Dellara F. Terry, MD, MPH, at Dovetail Health at 781-292-3581, may provide further information, as stated in the article.