Diabetes and the Elderly: Medication Considerations When Determining Benefits and Risks

Transcription

1 Diabetes and the Elderly: Medication Considerations When Determining Benefits and Risks Gretchen M. Ray, PharmD, PhC, BCACP, CDE Associate Professor UNM College of Pharmacy September 7 th, 2018

2 DISCLOSURES I do not have any relevant financial relationships with any commercial interests that create a conflict of interest to affect CME content about products or services

3 OBJECTIVES Describe general considerations when selecting drug therapy in an elderly population Describe the most commonly prescribed medications for diabetes and specific considerations when prescribing them to a geriatric population Discuss considerations when selecting pharmacotherapy options for hypertension and dyslipidemia in a geriatric diabetes patient Describe risks and considerations of select drugs used to treat diabetic neuropathy

4 RISK OF ADVERSE DRUG EVENTS IN OLDER ADULTS Increased risk of adverse drug events (ADEs) Multiple medications >20% of elderly use 5 or more medications Increased frequency of drug-drug interactions Decreased medication adherence Multiple comorbidities Age-related changes in drug pharmacokinetics Age-related changes in drug pharmacodynamics

5 Select Pharmacokinetic and Pharmacodynamic Considerations

6 AGING AND METABOLISM The liver is the most common site of drug metabolism Decrease in liver blood flow 40% to 45% with aging, related to cardiac function Increase in bioavailability Decreased 1 st pass effect = more parent drug Reduce initial dose, then titrate Decrease in liver size 20% to 50% decrease in absolute weight up to age 80 Reduction of total amount of metabolizing enzymes Leads to decrease in Cl and increase in t ½ Start with lower dosage Caution with toxic metabolites Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2:

7 ELIMINATION Most drugs exit body via kidney Reduced elimination = drug accumulation and toxicity Aging and certain geriatric disorders can impair kidney function Lower glomerular filtration rate (GFR) Reduced lean body mass = lower creatinine production and lower GFR SCr may appear to be in the normal range masking a reduction in CrCL BOTTOM LINE: calculate CrCl and egfr when dosing drugs in older patients Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2:

8 PHARMACODYNAMICS Time course and intensity of pharmacologic effect of a drug 1 Alteration and/or impairment can occur with aging but is highly variable from person to person 1 Inappropriate Medication use in Older Adults (2015 Beers Criteria update) 2 1. Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2: Beers criteria. J Am Geriatr Soc 2015

9 RISK FACTORS FOR ADES 6 or more concurrent chronic conditions 12 or more doses of drugs / day 9 or more medications Prior adverse drug reaction Low body weight or body mass index Age 85 or older Estimated CrCl < 50 ml / min Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2:

10 PRINCIPLES OF PRESCRIBING FOR OLDER PATIENTS: THE BASICS Start with a low dose Titrate upward slowly, as tolerated by the patient Avoid starting 2 drugs at the same time Consider deprescribing

11 ADE PRESCRIBING CASCADE DRUG 1 Adverse drug effectmisinterpreted as a new medical condition - DRUG 2 Adverse drug effectmisinterpreted as a new medical condition Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315(7115):1097.

12 BEFORE STARTING A NEW MEDICATION, ASK: Is this medication necessary? What are the therapeutic end points? Do the benefits outweigh the risks? Is it used to treat effects of another drug? Could 1 drug be used to treat 2 conditions? Could it interact with diseases, other drugs? Does patient know what it s for, how to take it, and what ADEs to look for?

13 Diabetes Management Medication Considerations

14 TREATMENT GOALS A1C <7.5% <8-8.5% in older adults with multiple chronic illnesses or cognitive impairment Avoidance of hypoglycemia Older adults are at higher risk for hypoglycemia Drug classes with low risk of hypoglycemia are preferred Standards of Medical Care in Diabetes Diabetes Care 2018;41(Suppl 1)

15 METFORMIN-ELIMINATION CONSIDERATIONS IN THE ELDERLY Low risk of hypopglycemia Calculate egfr at least annually In older adults a normal SCr does not necessarily indicate normal renal function Discontinue metformin when egfr 30 ml/min/1.73m 2 If already on therapy and egfr ml/min/1.73m 2 consider dose reduction of ½ the max dose

16 SULFONYLUREAS: HYPOGLYCEMIA CONSIDERATIONS Glyburide, glipizide, glimepiride High risk of hypoglycemia Glipizide is preferred Glyburide contraindicated in older adults per 2015 Beers Criteria Highest risk of hypoglycemia 2015 Beers criteria. J Am Geriatr Soc :

17 THIAZOLIDINEDIONES: ADVERSE EFFECT CONSIDERATIONS Pioglitazone and Rosiglitazone Benefits: low risk of hypoglycemia Risks: Contraindicated in heart failure patients Drug class associated with fractures Cautious use in patients at a high fall risk

18 DPP-4 INHIBITORS: COST CONSIDERATIONS Sitagliptin, saxagliptin, linagliptin, alogliptin Benefits: low risk of hypoglycemia, minimal side effects Risks/considerations: All except alogliptin are still brand name only Medicare part D patients often will enter into the donut hole mid-late year During that time these medications may be cost prohibitive

19 GLP-1 RECEPTOR AGONISTS Exenatide, liraglutide, dulaglutide, semaglutide Benefits: Low risk of hypoglycemia Potential for once weekly dosing Liraglutide (Victoza ) demonstrated significant reduction in major adverse cardiac events and cardiovascular death in high risk patients Risks/considerations: Feasibility of injection devices in setting of cognitive impairment or reduced motor skills Cost if patient is in the Medicare donut hole

20 SGLT2 INHIBITORS Empagliflozin, canagliflozin, dapagliflozin, ertugliflozin Benefits: Low risk of hypoglycemia Empagliflozin and canagliflozin demonstrated significant reduction in major adverse cardiac events Risks/considerations: Cost considerations if in the donut hole Volume depletion UTI/genital mycotic infection risk Must be renally dosed Regular monitoring of renal function

21 INSULIN Benefits: Once daily basal insulin overall low risk of hypoglycemia Availability of insulin pens Risks/considerations: Hypoglycemia risk Reliable independent administration in setting of cognitive decline/dementia

22 Hypertension Management in the Setting of Diabetes in an Older Adult

23 2018 ADA STANDARDS OF CARE: HYPERTENSION RECOMMENDATIONS Goal <140/90 mmhg <130/80 mmhg can be considered in patients at high CV risk Recommended 1 st line medications ACE-Inhibitors: lisinopril, fosinopril, etc Angiotensin receptor blockers(arbs): losartan, Irbesartan, canesartan, etc. Thiazide like diuretics: hydrochlorothiazide, chlorthalidone Dihydropyridine calcium channel blockers: amlodipine, felodipine Standards of Medical Care in Diabetes Diabetes Care 2018;41(Suppl 1)

24 ACE-INHIBITORS AND ARBS Pharmacodynamic considerations warranting increased monitoring Hyperkalemia Initial increase in SCr following drug initiation Drug-drug interactions NSAIDS + ACE-I or ARB: can cause acute kidney injury Extra caution in setting of dehydration or concurrent diuretic therapy

25 THIAZIDE- LIKE DIURETICS Chlorthalidone and hydrochlorothiazide Pharmacodynamic considerations Electrolyte disturbances: hyponatremia, hypokalemia, hypomagnesemia Hyperuricemia: gout exacerbation in a patient with pre-existing gout Pharmacokinetic considerations: Thiazide diuretics lose efficacy when CrCl <30ml/min Beers criteria suggest diuretics be used in caution in patients >65 years of age due to risk of hyponatremia or SIADH Beers criteria. J Am Geriatr Soc 2015

26 DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS Amlodipine, Felodipine Pharmacodynamic considerations and Adverse event profile: Increased blood pressure lowering response Always start with lowest dose and titrate slowly Peripheral edema

27 Lipid Management in the Setting of Diabetes in an Older Adult

28 ADA CHOLESTEROL TREATMENT RECOMMENDATIONS Age ASCVD Statin Dose Monitoring < 40 years >40 years No* none *Can consider Yes High # moderate intensity based on presence of risk factors No* Moderate *Can consider high Yes High # intensity based on presence of risk factors * Risk factors to consider: LDL 100 mg/dl, HTN, smoking, CKD, albuminuria, and family history of premature ASCVD # If pt has ASCVD and LDL is 70 mg/dl despite maximally tolerated statin dose, consider adding additional LDL-lowering therapy (ezetimibe or PCSK9 inhibitor) Standards of Medical Care in Diabetes Diabetes Care 2018;41(Suppl 1)

29 STATINS Pharmacodynamic considerations Older adults are at higher risk of statin induced myopathy Other risk factors include low vitamin D, uncontrolled hypothyroidism, drug-drug interactions with the statin Drug-drug interactions Statins are hepatically metabolized Many drugs can increase statin blood levels Atorvastatin, simvastatin, lovastatin- CYP3A4 Simvastatin and lovastatin-highest risk of interaction Rosuvastatin: CYP2C9 Pravastatin: not through CYP enzymes- lower risk of interaction Rosenson et al. J Clin Lipid 2014;8(35):S58-S71

30 Diabetic Peripheral Neuropathy Management in an Older Adult

31 DPN PHARMACOLOGIC TREATMENT-PAIN SYMPTOMS Consider Pregabalin (Lyrica ) or duloxetine (Cymbalta ) as initial approach Both have FDA indication for diabetic neuropathy Pregabalin is a α2-δ ligand Duloxetine is a SNRI Venlafaxine has same MOA and can be used, but has less evidence than duloxetine Gabapentin (α2-δ ligand) or tricyclic antidepressants (TCA) such as amitriptyline, nortriptyline or desipramine can also be used Often a combination of therapies is necessary Opioids including tramadol or tapentadol are not recommended as first or second line agents for painful DSPN symptoms Standards of Medical Care in Diabetes Diabetes Care 2018;41(Suppl 1)

32 2015 BEERS CRITERIA CONSIDERATIONS SPECIFIC TO NEUROPATHY MEDICATIONS Tricyclic antidepressants: Amitriptyline and nortriptyline Anticholinergic side effects Highly sedating Risk of orthostatic hypotension Increased risk of falls Gabapentin and Pregabalin Require renal dose adjustments if CrCl <60 ml/min SNRIs (duloxetine and venlafaxine) should be used with caution and close monitoring Risk of SIADH and hyponatremia 2015 Beers criteria. J Am Geriatr Soc 2015

33 CONCLUSIONS Age alters pharmacokinetics (drug absorption, distribution, metabolism, and elimination) Age alters pharmacodynamics ADEs are common among older patients Successful drug therapy means: Choosing the correct dosage of the correct drug for the condition and individual patient Monitoring the therapy Consider deprescribing when medications are potentially inappropriate or unnecessary

34 Questions