New drugs in the long-term care setting, part 1: a quick look at the benefits, uses and abuses of some recent candidates for LTC formularies. (Feature Article).

Lost in all the current debate over PPS, RUGs and prescription drug coverage is the fact that the pharmaceutical industry continues to make progress in developing new products for the long-term care market. Some have real potential for improving the wellbeing and quality of life of many residents. In this article and its next part in a future issue, I will explore these new agents, contrast their benefits with those of older agents and discuss the potential benefits of adding them to long-term care formularies. In this issue we will discuss drugs for decreasing cholesterol (hypolipidemics), managing diabetes (antidiabetics), treating infection (anti-infectives) and addressing mental health problems (psychotropics).

Hypolipidemics

While up to 70% of nursing facility residents have been shown to have hyperlipidemia that should be treated, there is increasing evidence that very few residents who might benefit from hypolipidemics actually receive appropriate therapy or reach consensus goals. These goals, for individuals with a history of target organ damage such as angina, myocardial infarction, stroke or diabetes, are levels of LDL cholesterol <100, triglycerides <50, and HDL cholesterol >40. There is also evidence for the cholesterol-lowering drugs called statins (Lipitor, Lescol, Mevacor, Pravachol and Zocor) that, when started in middle to later middle-age years, they reduce the risk of dementia, type 2 diabetes and osteoporosis.

There are some precautions. Hypolipidemic myopathy (meaning, in general, muscle aches and damage) is still a problem with the statins when used with the drugs Lopid, Tricor and Lipidil, and especially with niacin. This myopathy might also be seen with Mevacor and Zocor when erythromycin, Biaxin, Nizoral, Sporanox, cyclosporine, Serzone, protease inhibitors (for AIDS) or grapefruit juice are used with them. Pravachol and Lescol are the statins least affected by these drug-drug interactions.

The most potent statin yet developed, Crestor, is due to be released this year.

Antidiabetic Agents

Lantus is a newer insulin form that, unlike other regular or extended-release insulins, is meant to be given once a day at bedtime only. It is critical that this product not be delivered intravenously or mixed with other insulins. Patients on once-daily NPH insulin or Ultralente can be switched to the same dose of Lantus. Patients and caregivers should be warned that Lantus might sting more than NPH or other insulins because it is more acidic. They should also be told that Lantus is clear, not cloudy--which might be confusing, as prior diabetic teaching has emphasized that the NPH and Ultralente insulins are cloudy.

Starlix is a new, very-short-acting oral insulin stimulator for patients with type 2 diabetes (the most common form of diabetes in the elderly). It is meant to be given with meals that are consumed--in other words, if residents skip a meal, they should skip the pill. Starlix and a similar product called Prandin might have a unique use, i.e., for failure of other antidiabetic drugs, such as Micronase/Glynase, Diabeta or Glucotrol, when their maximal doses are reached and fasting glucose is no longer reduced appropriately.

Other medications for the diabetic. Evidence has shown that the heart drugs called ACE inhibitors and angiotensin receptor blockers (ARBs) spare insulin and preserve heart and kidney function. ACE inhibitors include Lotensin, captopril, enalapril, Monopril, Prinivil/Zestril, Univasc, Aceon, Accupril, Altace and Mavik. The ARBs are Atacand, Teveten, Avapro, Cozaar, Micardis and Diovan.

Metformin (Glucophage) is most useful as an insulin-sparing agent in younger type 2 diabetics, as long as their kidney function is adequate (creatinine clearance [CrCl] not less than 50 to 60 ml/min) and they do not have class II or higher congestive heart failure (CHF). Unfortunately, the average CrCl of most elderly ETC residents is 40 ml/min or less, and one-third or more have CHF. Recent studies have shown that prescribers do not take either CrCl or CHF into account when using metformin. When advanced CHF or reduced CrC1 is present, there is a much greater risk of lactic acidosis, which can be fatal in 20% or more of cases.

Actos and Avandia are secondary insulin-sparing drugs. They routinely cause fluid retention and might exacerbate CHF, but they can still be useful if HgA1c--a measure of blood glucose control over the previous 90 to 120 days--drops. A simple way to anticipate the fluid retention is to weigh the resident on Actos or Avandia daily for the first two weeks, then every other week throughout therapy. A five-pound or more weight gain or worsening foot swelling (pedal edema) should be reported to the prescriber to prevent acute pulmonary edema and hospital admission for CHF. The patient most likely to have new or worsened CHF is the patient using insulin. It might be most prudent to avoid Actos or Avandia in any patient requiring insulin.

Precose and Glyset are also insulin-sparing agents with a modest effect on HgA1c, but they require careful titration because of their excessive flatulence and laxative effect.

Anti-infectives

While amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX) (Septra/Bactrim), erythromycin and doxycycline are still flrstline drugs for upper and lower respiratory tract infections, it is important to save Ceftin, Vantin, Spectracef, Avelox, Levaquin and Tequin for cases involving resistant pneumococcus, Moraxella catarrhalis and Haemophilus influenzae. It is especially critical for clinicians to follow residents' renal function when they are receiving Tequin and Levaquin; otherwise, more confusion, delirium, disorientation and seizures will be seen, especially in those residents with a seizure or stroke history. It is critical for clinicians to restrict the use of Zyvox and save it for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) as it is the only oral drug that is effective against them.

Newer Psychotropics

Most of the newer atypical anti-psychotics (Risperdal, Zyprexa and Seroquel) are clearly safer and more cost-effective than the older antipsychotics (Mellaril, Thorazine, Stelazine and Haldol). Mellaril has been removed from the market in the United Kingdom as a result of retrospective evidence of a much higher rate of sudden cardiac deaths possibly related to its use.

Risperdal is the most used atypical. In as-yet-unpublished research I have conducted on the atypicals, Risperdal was the least sedating at 0.5 to 1.5 mg/day, and least likely to increase fall risk. Zyprexa was much more sedating, even at a lower dose of 2.5 to 10 mg/day, and the most likely of the three atypicals to increase falls. Seroquel was also sedating at the 25 to 100 mg/day recommended in older adults, and intermediate in fall risk.

Even the newer atypicals can affect the heart, and the newest atypical, Geodon, is not recommended in the elderly because of its association with arrhythmias.

A newly recognized problem--and potential benefit in the older adult--of the atypicals is weight gain. This might be beneficial in residents with significant psychoses and poor appetite. On the other hand, the weight gain might be so significant in well-nourished adults that new-onset type 2 diabetes or worsening diabetic control in previously well-controlled patients could be seen. Interestingly, this effect appears to occur in direct relation to the drugs' sedation effects (i.e., with Zyprexa, Seroquel and Risperdal).

Antidepressants are increasingly being used in long-term care residents for three reasons: (1) to treat depression or depressive symptoms, which might be seen in 30% or more of residents and can be an early indication of dementia; (2) to treat anxiety, depressive symptoms and agitation in early to midstage dementia; and (3) to replace or allow tapering of anti-anxiety agents called benzodiazepines (BZs). The BZs can be especially harmful to the elderly because they cause cognition and motor impairment, as well as fall risks, related to their length of action. For example, Valium, Librium, Tranxene, Centrax, Paxipam, Dalmane and Klonopin might be active for as long as 200 hours; Ativan, Xanax, Restoril and Doral are active for up to 24 hours; and Halcion and Serax, 6 to 9 hours.

Prozac has been moved to weekly dosing, which is appropriate because of its 10- to 14-day half-life at 20 to 90 mg. Preferred antidepressants in this class are (in daily doses) Celexa, 20 to 40 mg; Zoloft, 25 to 100 mg given in the morning only; Paxil, 10 to 40 mg; and Serzone, 50 to 150 mg, which can be administered at bedtime. All of these agents are probably equally effective for generalized anxiety disorder, as well as for unipolar depression and for tapering off BZs.

Wellbutrin and Serzone do not interfere with expression of sexuality, if this is important to the resident. Effexor raises blood pressure in some older adults and has to be dosed accordingly, but it might be useful in those residents who do not respond to other agents.

Inappropriate antidepressants for this population, according to the widely used Beer's Criteria, are amitriptyline and doxepin in any dose because of the fall and tachycardia risks they pose.

In Part 2, we will consider newer cognition-enhancing, gastrointestinal, pulmonary and osteoporosis medications.

James W. Cooper, RPh, PhD, is clinical editor of Nursing Homes/Long Term Care Management; professor and consultant pharmacist at the University of Georgia College of Pharmacy; and assistant clinical professor of family medicine, the Medical College of Georgia. For more information, phone [phone], fax [phone] or send e-mail to [e-mail].