 |
Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for elderly patients. Some, although reasonable for use in younger adults, are so risky as to be considered inappropriate for the elderly. The Beers Criteria are most commonly used to identify such inappropriate drugs (see Table 5: Drug Therapy in the Elderly: High-Risk Drugs in the Elderly (Based on the Beers Criteria) ). The Zhan expert panel further categorized some inappropriate drugs from the Beers Criteria into 3 groups:
|
Table 5
|
| | |
| High-Risk Drugs in the Elderly (Based on the Beers Criteria) |
|
Class
|
Drug
|
Prescribing Concern
|
|
Analgesics
|
Indomethacin*
|
Of available NSAIDs, indomethacin has the most CNS adverse effects and therefore should be avoided in the elderly.
|
|
|
Ketorolac
|
Immediate- and long-term use should be avoided in the elderly because many of them have asymptomatic and undiagnosed GI disorders.
|
|
|
Meperidine†
|
Meperidine is not an effective oral analgesic and has many disadvantages compared with other opioids. It should be avoided in the elderly.
|
|
|
Non–COX-selective NSAIDs (naproxen, oxaprozin, piroxicam)
|
Long-term use of the maximum dosage may cause GI bleeding, renal failure, hypertension, and heart failure.
|
|
|
Pentazocine†
|
Pentazocine is an opioid analgesic that has CNS adverse effects (eg, confusion, hallucinations) more commonly than other opioids; it is a mixed agonist/antagonist. For both reasons, it should usually be avoided in the elderly.
|
|
|
Propoxyphene‡ and combination products that contain it
|
Propoxyphene should usually be avoided in the elderly. It has few analgesic advantages over acetaminophen but has the adverse effects of other opioids.
|
|
Antidepressants
|
Cyclic antidepressants (eg, amitriptyline,* doxepin*)
|
Because of strong anticholinergic and sedating effects, amitriptyline or doxepin is rarely the antidepressant of choice for the elderly.
|
|
|
Fluoxetine (taken daily)
|
Fluoxetine has a long half-life, may cause excessive CNS stimulation and sleep disturbances, and may increase agitation. Safer alternative SSRIs exist.
|
|
Antihistamines
|
Chlorpheniramine*
Cyproheptadine*
Dexchlorpheniramine
Diphenhydramine*
Hydroxyzine*
Orphenadrine
Promethazine*
Tripelennamine
|
All OTC and many prescription antihistamines have potent anticholinergic properties. Antihistamines are commonly included with other drugs in cough and cold preparations. However, many cough and cold preparations without antihistamines are available; they are safer alternatives for the elderly.
|
|
Antipsychotics
|
Mesoridazine
Thioridazine
|
Risk of CNS and extrapyramidal adverse effects is increased. When used to treat dementia-related behaviors, 2nd-generation (atypical) antipsychotics may increase mortality risk.
|
|
Cardiovascular drugs
|
Amiodarone
|
Adverse effects include QTc prolongation and risk of provoking torsades de pointes.
|
|
|
Clonidine
|
Adverse effects include orthostatic hypotension and CNS effects.
|
|
|
Digoxin
|
Because renal clearance of digoxin is decreased in the elderly, doses should rarely exceed 0.125 mg/day, unless the patient is monitored.
|
|
|
Dipyridamole*
|
Immediate-release dipyridamole frequently causes orthostatic hypotension in the elderly (the controlled-release formulation in combination products may be acceptable). The immediate-release formulation is beneficial only in patients with artificial heart valves. If possible, it should be avoided in the elderly.
|
|
|
Disopyramide*
|
Of all antiarrhythmics, disopyramide is the most potent negative inotrope and therefore may induce heart failure in the elderly. It is also strongly anticholinergic. If antiarrhythmics are needed, others should be used.
|
|
|
Doxazosin
|
Adverse effects include hypotension, dry mouth, and urinary problems.
|
|
|
Ethacrynic acid
|
Adverse effects include hypertension and fluid imbalances.
|
|
|
Guanethidine
Guanadrel
|
Adverse effects include orthostatic hypotension.
|
|
|
Methyldopa*
|
Methyldopa may cause bradycardia and exacerbate depression in the elderly. Alternate treatments for hypertension are generally preferred.
|
|
|
Nifedipine (short-acting)
|
Adverse effects include hypotension, constipation, and reflex tachycardia.
|
|
|
Reserpine*
|
Doses > 0.25 mg pose unnecessary risks in the elderly by inducing depression, impotence, sedation, and orthostatic hypotension. Safer alternatives exist.
|
|
|
Ticlopidine
|
Ticlopidine is no better than aspirin in preventing clotting and is considerably more toxic. It should be used only as a 2nd-line drug in the elderly.
|
|
GI antispasmodics
|
Belladonna alkaloids†
Clidinium/chlordiazepoxide
Dicyclomine†
Hyoscyamine†
Propantheline†
|
GI antispasmodics are highly anticholinergic and usually cause substantial toxicity in the elderly. Efficacy at doses tolerated by the elderly is questionable. All of these drugs are best avoided in the elderly, especially for long-term use.
|
|
Hypoglycemics
|
Chlorpropamide†
|
Chlorpropamide has a prolonged half-life in the elderly and can cause prolonged, serious hypoglycemia. It is the only oral hypoglycemic that causes SIADH. It should be avoided in the elderly.
|
|
Laxatives (stimulant)
|
Bisacodyl
Cascara
Neoloid except when used with opioids
|
With long-term use, stimulant laxatives may exacerbate bowel dysfunction.
|
|
Muscle relaxants
|
Carisoprodol‡
Chlorzoxazone‡
Cyclobenzaprine‡
Metaxalone‡
Methocarbamol‡
Oxybutynin*
|
Most muscle relaxants and antispasmodics are poorly tolerated by the elderly, resulting in anticholinergic effects, sedation, and weakness. Efficacy at doses tolerated by the elderly is questionable. If possible, they should not be used in the elderly. For extended-release oxybutynin, the patch is better tolerated.
|
|
Sedative-hypnotics
|
Alprazolam*, § 2 mg
Lorazepam 3 mg
Oxazepam 60 mg
Temazepam 15 mg
Triazolam 0.25 mg
|
Because sensitivity to benzodiazepines is increased in the elderly, smaller doses may be effective as well as safer; total daily doses should rarely exceed those listed.
|
|
|
Barbiturates† (except phenobarbital)
|
Barbiturates have more adverse effects in the elderly than most other sedative-hypnotics and are highly addictive. They should not be started as new therapy in the elderly except to control seizures.
|
|
|
Chlordiazepoxide‡
Chlordiazepoxide/amitriptyline
Clorazepate
Clidinium/chlordiazepoxide
Diazepam‡
Flurazepam†
Halazepam
Nitrazepam
Quazepam
|
These long-acting benzodiazepines have a long half-life in the elderly (often days), causing prolonged sedation and increasing risk of falls and fractures. Short- or intermediate-acting benzodiazepines are preferred if a benzodiazepine is required.
|
|
|
Diphenhydramine
|
Diphenhydramine is potently anticholinergic and usually should not be used as a hypnotic in the elderly. When used to treat or prevent allergic reactions, it should be used in the smallest possible dose and with great caution.
|
|
|
Meprobamate
|
Meprobamate is a highly addictive and sedating anxiolytic. It should be avoided in the elderly. Elderly patients who take it for long periods may become addicted, and the drug may need to be withdrawn slowly.
|
|
Other
|
Amphetamines
Anorexics
|
These drugs may cause dependence, hypertension, angina, and MI. Amphetamines have CNS stimulant adverse effects (methylphenidate may be useful for certain elderly patients).
|
|
|
Cimetidine
|
Cimetidine has CNS adverse effects, including confusion.
|
|
|
Cyclandelate
Ergot mesylates
|
These drugs in the doses studied have not been shown to be effective for treatment of dementia or any other disorder.
|
|
|
Desiccated thyroid
|
Cardiac effects are a concern. Safer alternatives exist.
|
|
|
Estrogens only (oral)
|
Evidence suggests that estrogens increase risk of breast and endometrial cancer and may increase risk of pulmonary embolism, stroke, and coronary artery disease in older women.
|
|
|
Ferrous sulfate
|
Doses > 325 mg/day do not substantially increase total absorption and are more likely to cause constipation.
|
|
|
Isoxsuprine
|
Isoxsuprine is not effective in the elderly.
|
|
|
Methyltestosterone
|
Adverse effects include benign prostatic hypertrophy and cardiac problems.
|
|
|
Mineral oil
|
Mineral oil may result in aspiration.
|
|
|
Nitrofurantoin
|
Nitrofurantoin is ineffective in patients with moderate to severe renal insufficiency; metabolites may cause peripheral neuropathy. Long-term use for UTI prevention can cause pulmonary fibrosis.
|
|
|
Trimethobenzamide†
|
Trimethobenzamide is one of the least effective antiemetics and can have extrapyramidal adverse effects. When possible, it should be avoided in the elderly.
|
|
*Sometimes indicated but often misused according to the Zhan panel.
|
|
†Always to be avoided according to the Zhan panel.
|
|
‡Rarely appropriate according to the Zhan panel.
|
|
§Doses of alprazolam may be higher when used to treat panic disorders.
|
|
COX = cyclooxygenase; SIADH = syndrome of inappropriate antidiuretic hormone secretion.
|
|
Analgesics:
NSAIDs are used by > 30% of people aged 65 to 89, and half of all NSAID prescriptions are for people > 60. Several NSAIDs are available without prescription.
The elderly may be prone to adverse effects of these drugs, and adverse effects may be more severe because of the following:
Serious adverse effects include peptic ulceration and upper GI bleeding; risk is increased when an NSAID is begun and when dose is increased. Risk of upper GI bleeding increases when NSAIDs are given with warfarin, aspirin, or other antiplatelet drugs (eg, clopidogrel). NSAIDs may increase risk of cardiovascular events and can cause fluid retention and, rarely, nephropathy.
NSAIDs can also increase BP; this effect may be unrecognized and lead to intensification of antihypertensive treatment (a prescribing cascade). Thus, clinicians should keep this effect in mind when BP increases in elderly patients and ask them about their use of NSAIDs, particularly OTC NSAIDs.
Selective COX-2 (cyclooxygenase-2) inhibitors (coxibs) cause less GI irritation and platelet inhibition than other NSAIDs. Nonetheless, coxibs have a risk of GI bleeding, especially for patients taking warfarin or aspirin (even at a low dose) and for those who have had GI events. Coxibs, as a class, appear to increase risk of cardiovascular events, but risk may vary by drug; they should be used cautiously. Coxibs have renal effects comparable to those of other NSAIDs.
Lower-risk alternatives (eg, acetaminophen) should be used when possible. If NSAIDs are used in the elderly, the lowest effective dose should be used, and continued need should be reviewed frequently. If NSAIDs are used long-term, serum creatinine and BP should be monitored closely, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use).
Anticoagulants:
Aging may increase sensitivity to the anticoagulant effect of warfarin. Careful dosing and scrupulous monitoring can largely overcome the increased risk of bleeding in elderly patients taking warfarin. Also, because drug interactions with warfarin are common, closer monitoring is necessary when new drugs are added or old ones are stopped; computer drug interaction programs should be consulted if patients take multiple drugs.
Antidepressants:
Tricyclic antidepressants are effective but should rarely be used in the elderly. SSRIs and mixed serotonin/dopamine reuptake inhibitors are as effective as tricyclic antidepressants and cause less toxicity; however, there are some concerns about some of these drugs:
Doses of these drugs should be reduced by up to 50%. Many SSRIs are available, but data on their use in the elderly are sparse.
Antihyperglycemics:
Doses of antihyperglycemics should be titrated carefully in patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase with age. Chlorpropamide is not recommended because elderly patients are at increased risk of hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and because the drug's long duration of action is dangerous if adverse effects or hypoglycemia occurs. Risk of hypoglycemia is greater with glyburide than with other oral antihyperglycemics because like chlorpropamide, it is eliminated by the kidneys, and clearance can be reduced when renal function is impaired.
Metformin, a biguanide excreted by the kidneys, increases peripheral tissue sensitivity to insulin and can be effective given alone or with sulfonylureas. Risk of lactic acidosis, a rare but serious complication, increases with degree of renal impairment and with patient age. Heart failure is a contraindication.
Antihypertensives:
In many elderly patients, lower starting doses of antihypertensives may be necessary to reduce risk of adverse effects; however, for most elderly patients with hypertension, achieving BP goals requires standard doses and multidrug therapy. Initially, a thiazide-type diuretic is usually given alone or with one of the other classes shown to be beneficial (ACE inhibitors, angiotensin II receptor blockers, β-blockers, Ca channel blockers). Short-acting dihydropyridines (eg, nifedipine) may increase mortality risk and should not be used. Sitting and standing BP can be monitored, particularly when multiple antihypertensives are used, to check for orthostatic hypotension, which may increase risk of falls and fractures.
Antiparkinsonian drugs:
Levodopa clearance is reduced in elderly patients, who are also more susceptible to the drug's adverse effects, particularly orthostatic hypotension and confusion. Therefore, elderly patients should be given a lower starting dose of levodopa and carefully monitored for adverse effects (see Movement and Cerebellar Disorders: Levodopa). Patients who become confused while taking levodopa may also not tolerate newer dopamine agonists (eg, pramipexole, ropinirole). Because elderly patients with parkinsonism may be cognitively impaired, anticholinergic drugs should be avoided.
Antipsychotics:
In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than placebos and can have severe adverse effects. Antipsychotics should be reserved for psychosis.
When an antipsychotic is used, the starting dose should be about one quarter the usual starting adult dose and should be increased gradually. Clinical trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited.
Antipsychotics can reduce paranoia but may worsen confusion (see also Schizophrenia and Related Disorders: Conventional antipsychotics). Elderly patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. Sedation, orthostatic hypotension, anticholinergic effects, and akathisia (subjective motor restlessness) can occur in up to 20% of elderly patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6 to 9 mo after the drug is stopped.
The FDA has issued a warning regarding the use of 2nd-generation (atypical) antipsychotics, once thought to be safer, in the treatment of behavioral disorders in elderly patients with dementia; a review of placebo-controlled studies has shown a higher mortality rate associated with their use. Extrapyramidal dysfunction can develop when 2nd-generation antipsychotics (eg, olanzapine, quetiapine, risperidone) are used, especially at higher doses. Risks and benefits of using an antipsychotic should be discussed with the patient or the person responsible for the patient's care.
Anxiolytics and hypnotics:
Treatable causes of insomnia should be sought and managed before using hypnotics (see also Sleep and Wakefulness Disorders: Hypnotics). Nonpharmacologic measures and sleep hygiene (eg, avoiding caffeinated beverages, limiting daytime napping, modifying bedtime) should be tried first. If they are ineffective, nonbenzodiazepine hypnotics (eg, the imidazopyridines, alpidem and zolpidem) are options. These drugs bind mainly to a benzodiazepine receptor subtype. Imidazopyridines disturb the sleep pattern less than benzodiazepines and have a more rapid onset, fewer rebound effects, fewer next-day effects, and less potential for dependence. Short- or intermediate-acting benzodiazepines with half-lives of < 24 h (eg, alprazolam, lorazepam, oxazepam, temazepam) are preferable to long-acting benzodiazepines but may have adverse effects, including those that lead to falls and fractures.
Longer-acting benzodiazepines (eg, clonazepam, diazepam, flurazepam) should be avoided because they have active metabolites, are likely to accumulate, and have adverse effects (eg, drowsiness, impaired memory, impaired balance leading to falls and fractures).
Duration of anxiolytic or hypnotic therapy should be limited if possible because tolerance and dependence may develop; withdrawal may lead to rebound anxiety or insomnia.
Antihistamines (eg, diphenhydramine, hydroxyzine) are not recommended as anxiolytics or hypnotics because they have anticholinergic effects.
Buspirone, a partial serotonin agonist, can be effective for general anxiety disorder; elderly patients tolerate doses up to 30 mg/day well. The slow onset of anxiolytic action (up to 2 to 3 wk) can be a disadvantage in urgent cases.
Digoxin:
Digoxin, a cardiac glycoside, is used to increase the force of myocardial contractions and to treat supraventricular arrhythmias. However, it must be used with caution in patients with heart failure. In men with heart failure and a left ventricular ejection fraction of ≤ 45%, serum digoxin levels > 0.8 ng/mL are associated with increased mortality risk. Adverse effects are typically related to its narrow therapeutic index. One study found digoxin to be beneficial in women when serum levels were 0.5 to 0.9 ng/mL but possibly harmful when levels were ≥ 1.2 ng/mL. A number of factors increase the likelihood of digoxin toxicity in the elderly. Renal impairment, temporary dehydration, and NSAID use (all common among the elderly) can reduce renal clearance of digoxin. Furthermore, digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Also, if lean body mass is reduced, as may occur with aging, volume of distribution for digoxin is reduced. Therefore, starting doses should be low (0.125 mg/day) and adjusted according to response and serum digoxin levels (normal range 0.8 to 2.0 ng/mL). However, serum digoxin level does not always correlate with likelihood of toxicity.
Diuretics:
Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension in many elderly patients and have less risk of hypokalemia and hyperglycemia than other diuretics (see also Hypertension: Diuretics). Thus, K supplements may be required less often.
K-sparing diuretics should be used with caution in the elderly; the K level must be carefully monitored, particularly when these diuretics are given with ACE inhibitors.
Last full review/revision September 2009 by J. Mark Ruscin, PharmD
Content last modified September 2009
| |
|
