Polypharmacy in the HIV-infected older adult population

Figures & data

Table 1 Summary of drug-drug interaction with HAART and various drug classes^{4,6,48,68,135}

Drug class	PIs	Nature of interaction	Recommended adjustments	NNRTIs	Nature of interaction	Recommended adjustments
Cardiovascular medications
HMG-CoA reductase inhibitors, statins	Mostly all PIs, (nelfinavir, fosamprenavir, ritonavir, indinavir, saquinavir, lopinavir)	Increased level of statins with potential for rhabdomyolysis	Contraindicated lovastatin and simvastatin	Etravirine, delavirdine, efavirenz, nevirapine	Possible decreased level of statins	Higher dose of atorvastatin or pravastatin might be needed
			Dose adjustments: atorvastatin and rosuvastatin
			No adjustments for pravastatin or fluvastatin
Digoxin	Ritonavir, saquinavir/ritonavir	Increased level digoxin and half-life	Use with caution, monitor digoxin levels, digoxin dose might need to be decreased
Dihydropyridine CCBs	All PIs	Increase serum levels of CCBs, increasing risk of hypotension, conduction block, bradycardia	Use with caution, reduce dose of CCB, titrate carefully or avoid, monitor ECG	Efavirenz, nevirapine	Decrease CCBs serum concentrations through inhibition	Dose adjustment to steady state may be needed, titrate based on clinical response
Antiarrhythmic	All PIs, especially ritonavir boosted	Increased levels of antiarrhythmic serum concentrations	Contraindicated with ritonavir boosted PI: amiodarone, bepridil, flecainide, propafenone, and quinidine
			Approach use of with caution: disopyramide, dofetilide, lidocaine, mexiletine, procainamide
Warfarin	Interacts with most PIs	Alter S-warfarin concentrations	Monitor INR closely and adjust dose as needed	Efavirenz, nevirapine may increase or decrease levels of warfarin Etravirine may increase levels of warfarin	Alter S-warfarin concentrations	Monitor INR closely and adjust dose as needed
			Use tipranavir with caution increased risk of bleeding	Etravirine may increase levels of warfarin
Clopidogrel	Interaction is unlikely with PIs			Etravirine	May decrease formation of active Clopidogrel metabolite	Avoid coadministration of clopiogrel and etravirine
Gastrointestinal medications
H2 blockers	Boosted atazanavir, boosted atazanavir with tenofovir, unboosted atazanavir	Increased levels of H2 blocker and decreased levels of PIs – impaired absorption of drugs which require acid environment	Avoid Cimetidine Separate administration – ≥ 10 hours after H2 blockers	Rilpivirine	H2 blocker can decrease antiretroviral serum concentration	Give H2 blocker ≥ 12 hours before or ≥4 hours after rilpivirine
PPIs	Boosted PIs	Altered drug levels of PIs and HAART treatment	Avoid PPI use of atazanavir, nelfinavir	Rilpivirine	PPI decreases effect concentration	PPI contraindicated with rilpivirine – do not coadminister
			PPI dose should not exceed more than 20 mg/day of omeprazole if administered with atazanavir, nelfinavir PPI should be given at least 12 hours prior to HAART; PPI not recommended with unboosted atazanavir
Genitourinary medications
5-α reductase inhibitors	Minimal interactions with PIs	Dutasteride concentrations may be increased	Consider finasteride, monitor for decreased libido and erectile dysfunction
Alpha adrenergic antagonist	Boosted PIs	Increases concentration of á-adrenergic antagonist; Increasing risk of orthostatic hypotension	Alfuzosin contraindicated, monitor tamsulosin with first dose and consider dose reduction; minimal effect with doxazosin and prazosin
Phosphodiesterase-5 inhibitors: sildenafil, tadalafil, vardenafil	Most PIs	Increase in levels of PDE-5 inhibitors, increased risk of unsafe drop in blood pressure	Decrease dose of PDE-S inhibitors; sildenafil: do not exceed 25 mg in 48 hours tadalafil: do not exceed 10 mg in 72 hours	Etravirine	Possible increase in levels of PDE-S inhibitors	May need to increase dose based on clinical effect; coadministration is not recommended with avanafil
Psychiatric/neurologic medications
Antidepressant: SSRIs	PIs	Increased levels of some SSRIs and increased levels of PIs	Monitor closely and may require lower dose of SSRI; escitalopram and Citalopram are preferred SSRIs	Efavirenz, nevirapine	Decreases concentrations; nevirapine can decrease fluoxetine, efavirenz decrease sertraline	Titrate SSRI to effect, escitalopram and Citalopram are preferred SSRIs
TCAs	All ritonavir boosted PIs	Increased levels of TCA which can results in orthostatic hypotension and anticholinergic side effects	Use with caution with lopinavir and ritonavir boosted PIs, monitor for adverse effects, or consider alternative antidepressant	Rilpivirine, increased concentration of TCA; efavirenz decreases sertraline dose		Avoid rilpivirine coadministration with TCA due to risk of additive QT prolongation, consider alternative antidepressant
Trazodone	Nearly all PIs	Increased level of trazodone	Monitor for CNS and cardiovascular effects, contraindicated with saquinavir
Bupropion	Lopinavir boosted and tipravnavir boosted	Decreased amount of bupropion	Titrate bupropion dose based on clinical response	Efavirenz	Decreases concentration of buproprion	Titrate buproprion dose based on clinical response
Benzodiazepine	All PIs	Increased levels of benzodiazepines alprazolam, clonazepam, diazepam, flurazepam, midazolam, triazolam	Midazolam and triazolam contraindicated with boosted PIs; can use other benzodiazepines	Efavirenz	Increases levels of midazolam, triazolam, diazepam; no data on alprazolam	Avoid use of midazolam and triazolam coadministration with efavirenz
Antimyobacterials/antifungals
Clarithromycin	Boosted PIs, atazanavir	Increased clarithromycin concentration	Monitor for clarithromycin related toxicities, may concern alternative macrolide (azithromycin); monitor QtC; dose reduction for renal failure	Efavirenz, etravirine, nevirapine, rilpivirine	Decreased concentration of clarithromycin	Consider alternative agent, such as azithromycin, monitor for effectiveness
Rifampin	All PIs	Decreases PI concentration by greater than 75%	Do no coadminister rifampin and PIs, ritonavir increases hepatotoxicity	Efavirenz, etravirine, nevirapine, rilpivirine	Decreased NNRTIs	Contraindicated with etravirine, nevirapine, rilpivirine
Azoles	All PIs	Altered levels of azoles and PIs	Fluconazole may be better alternative but use with caution with tipranavir	NNRTIs	Alerted levels of azoles and NNRTIs	Fluconazole best option, avoid others if able to
Steroids
Budesonide (systemic, inhaled, intranasal)	All PIs	Increased glucocorticoids ad decreased PIs	Use with caution. Do not coadminister unless potential benefits of systemic, inhaled, intranasal outweigh risk of systemic corticosteroid adverse effect. Coadministration can result in adrenal insufficiency, Cushing’s syndrome
Prednisone	Boosted lopinavir	Decrease lopinavir and increased prednisolone	Use with caution. Coadministration can result in adrenal insufficiency, Cushing’s syndrome
Narcotic pain medications
Oxycodone	Lopinavir/ritonavir	Increased levels oxycodone	Monitor for opioid-related adverse effects. Oxycodone dose reduction may be needed
Methadone	Darunavir, lopinavir, nelfinavir, tipranavir	Decreased levels of methadone	Monitor for signs of opioid withdrawal, may require increased dose of methadone	Efavirenz, nevirapine	Decreased levels of methadone	Monitor for signs of opioid withdrawal, may require increased dose of methadone

Abbreviations: HAART, highly active antiretroviral therapy; PI, protease inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; HMG-CoA, 5-hydroxy-3-methylglutaryl-coenzyme A; CCB, calcium channel blocker; ECG, electrocardiogram; INR, international normalized ratio; PPI, proton pump inhibitor; PDE-5, phosphodiesterase type 5; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; CNS, central nervous system.

Table 2 General considerations for managing polypharmacy in older adults

• Throughout medication history

○ “Brown Bag” asking patient to bring in all prescription, OTC, and herbal medications

▪ “Teach-back” method, patient shows how taking medication

○ Determine patient adherence to medication and barriers if not adherent

▪ Is the patient forgetting to take?

▪ Is the pill difficult to take?

▪ Is the pill costly?

▪ Does the patient believe that the drug is not needed?

○ Where possible use the same pharmacy

• Indications for current medications

○ Determine if medication is on Beers List or Medication Appropriateness Index

○ Is the dosage correct?

• Review drug–drug interactions

• Determine the therapeutic ratio

○ Start low and go slow for titration up

• Good communication with other healthcare providers (physicians and caregivers)

Abbreviation: OTC, over-the-counter.

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