INTERAZIONE TRA FARMACI: CASI CLINICI A CONFRONTO · STATIN USE IN VERY ELDERLY INDIVIDUALS,...

INTERAZIONE TRA FARMACI:

CASI CLINICI A CONFRONTO

FEDERICO PEA

ISTITUTO DI FARMACOLOGIA CLINICA

AZIENDA OSPEDALIERO UNIVERSITARIA SM MISERICORDIA

UDINE

Arta Terme, 20 Aprile 2016Udine, 02 Maggio 2016

Istituto di Farmacologia Clinica - UniUD

INTERAZIONE FARMACOCINETICA:

UN CASO CLINICO

MASCHIO, 64 AA, INSUFFICIENZA RENALE CRONICA

-6 mesi: ipercolesterolemia

START TERAPIA CON SIMVASTATINA

-3 settimane: sinusite

START TERAPIA CON CLARITROMICINA

Giorno 0: dolore muscolare diffuso, severa miastenia, anuria

RICOVERO: Esami laboratorio: >>> CPKBiopsia muscolare: miopatia necrotizzante

DIALISI a giorni alterni

MORTE PER COMPLICANZE INFETTIVE DOPO 3 MESI

RHABDOMYOLYSIS SECONDARY TO A DRUG INTERACTION BETWEEN

SIMVASTATIN AND CLARITHROMYCINLee AJ and Maddix DS. Ann Pharmacother: 2001; 35: 26–31.


STORY FROM THE FRONT LINES

• An 86-year-old woman with moderate dementia, depression, and

osteoporosis fell and experienced a vertebral compression fracture at her

assisted-living facility.

• Prior to the fall she was ambulatory with a walker and enjoyed socializing

with her friends and family.

• During the week after the fall, while taking escalating dosages of opioids

for pain, she walked less and less and suffered from constipation.

• In the following days, she became withdrawn and repeatedly called out

“Help me!” for unclear reasons.

• She was started on diazepam and haloperidol, but her vocalizations

increased and her cognition worsened.

• Over the next week, she stopped walking and developed a pressure ulcer.



• When she developed dysphagia and weight loss, she was enrolled in hospice

• When the patient became chair- and bed-bound, she was seen by a “house

calls” geriatrician who evaluated her and suspected

POLYPHARMACY

• Hospice was discontinued.

• Haloperidol and opioids were stopped and diazepam tapered off.

• Her caregivers were educated to provide a daily routine and to speak

calmly.

• When she called for help, if her needs (eg, toileting, eating, or pain

relief) had been addressed, she was redirected to other activities, such as

looking through family photographs or listening to music.

• Home physical, occupational, and speech therapy provided rehabilitation to

help her regain her strength, mobility, and swallowing and to educate her

caregivers.



• The patient was started on citalopram hydrobromide for anxiety, melatonin

for sleep, and acetaminophen for pain.

• Within 4 months, her repeated vocalizations stopped, and she returned to

her prefill functional status.

• She began walking again, participating in activities, and eating and sleeping

well.

• She recently celebrated her 87th birthday with her family.


• This case highlights the risk of polypharmacy in the treatment of

neuropsychiatric symptoms, the complexity of prognostication in dementia,

and the importance of a multifaceted approach to neuropsychiatric

symptoms, including addressing triggers, providing behavioral interventions,

and cautious use of medications.

CONCLUSIONS


POLITERAPIE

E INAPPROPRIATEZZE PRESCRITTIVE

AMERICAN GERIATRICS SOCIETY UPDATED BEERS CRITERIA FOR

POTENTIALLY INAPPROPRIATE MEDICATION USE IN OLDER ADULTSAmerican Geriatrics Society 2012 Beers Criteria Update Expert Panel

J Am Geriatr Soc. 2012 Apr;60(4):616-31

RESULTS

• 53 medication or medication classes encompass the final updated 2012 AGS Beers

Criteria, which are divided into three categories:

• 34 potentially inappropriate medications and classes to avoid in older adults.

• potentially inappropriate medications and classes to avoid in older adults with certain

diseases and syndromes that the drugs listed can exacerbate.

• 14 medications and classes to be used with caution in older adults.

POLYTHERAPY AND THE RISK OF POTENTIALLY INAPPROPRIATE PRESCRIPTIONS (PIPS) AMONG ELDERLY AND VERY ELDERLY PATIENTS

IN THREE DIFFERENT SETTINGS OF THE FRIULI VENEZIA GIULIA REGION, ITALYPiergiorgio Cojutti, Luca Arnoldo, Giovanni Cattani, Silvio Brusaferro, Federico Pea

Pharmacoepidemiol Drug Safety 2016 in press

PATIENTS’ CHARACTERISTICS

POLYTHERAPY AND THE RISK OF POTENTIALLY INAPPROPRIATE PRESCRIPTIONS (PIPS) AMONG ELDERLY AND VERY ELDERLY PATIENTS

IN THREE DIFFERENT SETTINGS OF THE FRIULI VENEZIA GIULIA REGION, ITALYPiergiorgio Cojutti, Luca Arnoldo, Giovanni Cattani, Silvio Brusaferro, Federico Pea

Pharmacoepidemiol Drug Safety 2016 in press

FACTORS ASSOCIATED AT MULTIVARIATE ANALYSIS WITH POTENTIALLY INAPPROPRIATE PRESCRIPTION (PIP)

ECONOMIC AND SOCIAL IMPLICATIONS OF AGING SOCIETIES Harper S. Science 2014 Oct 31; 346: 587-91

WORLD POPULATION PYRAMIDS


NATIONAL SURVEILLANCE OF EMERGENCY DEPARTMENTVISITS FOR OUTPATIENT ADVERSE DRUG EVENTS

Budnitz DS et al. JAMA 2006; 296: 1858-1866

ESTIMATED ANNUAL INCIDENCE OF ADVERSE DRUG EVENTS TREATED

IN US EMERGENCY DEPARTMENTS VS AGE

Active surveillance Jan 2004 - Dec 2005

21.298 adverse drug event cases

3487 individuals required hospitalization


NATIONAL SURVEILLANCE OFEMERGENCY DEPARTMENTVISITS FOR OUTPATIENT ADVERSE DRUG EVENTS

Budnitz DS et al. JAMA 2006; 296: 1858-1866

LEADING CAUSES OF ADVERSE DRUG EVENTS


PREVALENCE, CLINICAL FEATURES AND AVOIDABILITY OF ADRs

AS CAUSE OF ADMISSION TO A GERIATRIC UNIT

A PROSPECTIVE STUDY OF 1756 PATIENTSFranceschi M et al. Drug Saf 2008; June, 31 (6): 545-556

ASSESSMENT OF AVOIDABILITY OF ADRs

In the elderly, almost 6% of hospitalizations are ADR related.

Most of these ADRs are potentially avoidable.

nov 2004 to dec 2005

DEFINITION

WHAT DOES FRAIL ELDERLY PERSONS MEAN ?

• Frailty can be defined as an increased risk of adverse effects

due to a decline in functional reserves and somatic, psychological

and social limitations.

• Frailty is an important factor in inappropriate prescribing in

elderly patients

Rockwood K et al. Drugs Aging 2000; 17: 295-302

Gobbens RJ et al. J Nutr Health Aging 2010; 14: 175-81

Fried LP et al. J Gerontol A Biol Sci Med Sci 2004; 59: 255-63


HIGH-RISK PRESCRIBING AND INCIDENCE OF FRAILTYAMONG OLDER COMMUNITY-DWELLING MEN

Gnjidic C et al. Clin Pharmacol Ther 2012; 91: 521-528

ODDS RATIOS OF HIGH-RISK PRESCRIBING BY FRAILTY STATUS AT BASELINE


HIGH-RISK PRESCRIBING AND INCIDENCE OF FRAILTYAMONG OLDER COMMUNITY-DWELLING MEN

Gnjidic C et al. Clin Pharmacol Ther 2012; 91: 521-528

ODDS RATIOS RELATING HIGH-RISK PRESCRIBING TO RISK OF FRAILTY OVER 2-YEAR FOLLOW-UP PERIOD (N = 1,242)

WHICH SPECIFIC ISSUES

IN THE FRAIL ELDERLY PATIENTS ?

RELEVANT CONSIDERATIONS FOR CHOICE OF PHARMACOTHERAPY IN FRAIL ELDERLY PERSONS

CRITERIA FOR DRUG SELECTION IN FRAIL ELDERLY PERSONSHuisman-Baron M et al. Drugs Aging 2011; 28 (5): 391-402

INCIDENZA (%) DELLE PRINCIPALI VIE DI ELIMINAZIONE DEI FARMACI

Pea F. Farmacocinetica: utilità nella pratica clinica quotidiana. 2007; Seed Editore, Torino


THE EFFECT OF DRUG METABOLISM ON EXCRETION

Weinshilboum R. N Engl J Med 2003; 348: 529-537

VALUTAZIONE PERIODICA DELLA FUNZIONE RENALE


https://www.kidney.org/apps/egfr-calculator


concealed renal insufficiency:

estimated CLCr < 60 mL/min and SCr ≤ 1.2 mg/dL

N = 11687

CONCEALED RENAL INSUFFICIENCY AND ADVERSE DRUG REACTIONS IN ELDERLY HOSPITALIZED PATIENTSCorsonello A et al. Arch Intern Med 2005; 165: 790-795

SUMMARY REGRESSION MODELS OF SELECTED RISK FACTORS TO THE OCCURRENCE OF ADR DURING HOSPITAL STAY

Institute of Clinical Pharmacology - UniUD

WHICH MECHANISMS ARE RESPONSIBLE

FOR PK DRUG-DRUG INTERACTIONS DURING POLYTHERAPHY ?

Institute of Clinical Pharmacology - UniUD

METABOLIC PATHWAYS OF LIPOPHILIC DRUGS

RED-OX BY MEANS OF CYP450

Relative importance of each isoform

• CYP450 microsomial system isresponsible for most Phase Imetabolic reactions

• 12 isoenzyme families are expressedin humans

• Several classes of drugs aresubstrates of CYP450, but all arecharacterized by considerablelipophilicity

• CYP3A4 is the major isoform inhumans and is consistently expressedalso in the intestinal mucosa

CYP 3A4CYP 2D6

CYP2C9-19

CYP 1A2 CYP 2E1


FOS x DOSE

CL

AUC =

↑ FOS

↑ AUC

↓ FOS

ESPOSIZIONE PLASMATICA E DOSE DI MANTENIMENTO (MD)

AUC

Concentrazione farmaco (µg/mL) Cmax

Cmin

Intervallo tra le dosi

↑ AUC

THERAPEUTICFAILURE

DRUGTOXICITY

↓ AUC

=

↓ AUC


F x DOSE

CL

AUC =↑ AUC

↓ CL

↓ AUC

↑ CL

ESPOSIZIONE PLASMATICA E DOSE DI MANTENIMENTO (MD)

AUC

Concentrazione farmaco (µg/mL) Cmax

Cmin

Intervallo tra le dosi

↑ AUC

↓ AUC

THERAPEUTICFAILURE

DRUGTOXICITY

=


CYP3A4-5•Macrolidi

•Benzodiazepine (alprazolam, midazolam, triazolam)

• Farmaci immunosoppressori (ciclosporina, everolimus, sirolimus, tacrolimus)

•Antiepilettici (carbamazepina)

•Analgesici oppiacei (alfentanil, fentanil, sufentanil)

•Antiaritmici (disopiramide, quinidine,

amiodarone)

•Calcio-antagonisti

(felodipina, nifedipina)

•R-warfarin

•Corticosteroidi (metilprednisolone)

•Inibitori dell’HMG-CoA reduttasi (lovastatina, simvastatina)

CYP2D6•Beta-bloccanti

(metoprololo, propranololo,

timololo)

•Antidepressivi

(amitriptilina,

clomipramina, desipramina,

imipramina)

•Antipsicotici

(tioridazina)

CYP2C19•Antiepilettici

(fenitoina)

•Inibitori della pompa

protonica (lansoprazolo,

omeprazolo)

•Altri

(diazepam, imipramina)

CYP2C9•Antiepilettici(fenitoina)

•S-warfarin•FANS(diclofenac, flurbiprofene,ibuprofene, naproxene, piroxicam)

•Ipoglicemizzanti orali(sulfaniluree: tolbutamide, glipizide)

•Bloccanti angiotensina II(losartan, irbesartan)

CYP1A2•Teofillina

•Verapamil

•R-warfarin

•Aloperidolo

•Naproxene

•Ondansetron

•Propranololo

CYP INIBITORICimetidinaFluorochinoloniFluvoxamina

x

Ac valproico FluorochinoloniMacrolidiSucco di pompelmoTriazoli

x

FluconazoloFluoxetinaFluvastatinaParoxetina

x

AmitriptilinaFenitoinaKetoconazoloImipramina

x

AloperidoloChinidinaFluoxetinaParoxetina

x

Pea F. & Furlanut M. Clin Pharmacokinet 2001; 11: 833-68

PK ASPECTS OF TREATING INFECTIONS IN THE INTENSIVE CARE UNITFOCUS ON DRUG INTERACTIONS

Pea F and Furlanut M. Clin Pharmacokinet 2001; 40: 833-868

Institute of Clinical Pharmacology and Toxicology – University of Udine – Italy

GENERAL CONCEPT OF THE IN VIVO BASED PREDICTION OF AUC INCREASES CAUSED BY INHIBITION OF CYP3A4


GRAPEFRUIT-DRUG INTERACTIONS:

CAN INTERACTIONS WITH DRUGS BE AVOIDED? Mertens-Talcott SU et al. J Clin Pharmacol 2006;46: 1390-1416

FLAVONOIDS

BERGAMOTTIN 6´7´-DIHYDROXYBERGAMOTTIN

NARINGENIN NARINGIN

FURANOCOUMARINS-DIMER GF-I-1

UniUd

SUCCO DI POMPELMO E FELODIPINA

Dresser GK et al Clin Pharmacol Ther 2000;68(1):28–34

Hours after Dose Hours after Dose


SUCCO DI POMPELMO E FELODIPINA

Wilkinson GR. New Engl J Med 2005; 352: 2211-2221


CONCURRENT USE OF WARFARIN AND ANTIBIOTICS AND THE RISK OF BLEEDING IN OLDER ADULTS

Baillargeon J et al. Am J Med 2012; 125: 183-189

BASELINE CHARACTERISTICS FOR CASES AND MATCHED CONTROLS


ASSOCIATION BETWEEN SPECIFIC ANTIBIOTIC AGENT EXPOSURE AND HOSPITALIZATION FOR BLEEDING

CONCURRENT USE OF WARFARIN AND ANTIBIOTICS AND THE RISK OF BLEEDING IN OLDER ADULTS

Baillargeon J et al. Am J Med 2012; 125: 183-189

SOC Farmacologia Clinica – AOUD

HYPOGLYCEMIA AFTER ANTIMICROBIAL DRUG PRESCRIPTION

FOR OLDER PATIENTS USING SULFONYLUREASParekh TM et al. JAMA Intern Med 2014 Sep 1 on line published

STUDY DESIGN

• Years 2006 to 2009 for Texas Medicare beneficiaries

• All prescriptions for glipizide or glyburide.

• Those with concurrent use of any oral antimicrobial agent

• Beneficiaries ≥ 66 years

• Hospitalization or emergency department visits due to hypoglycemia within 14 days of

antimicrobial exposure




ANTIMICROBIAL DRUGS STUDIED AND THE EXISTING EVIDENCE FOR INTERACTION WITH SULFONYLUREAS




ASSOCIATION OF PATIENT CHARACTERISTICS AND ANTIMICROBIAL DRUG EXPOSURE WITH HYPOGLYCEMIC EVENTS AMONG GLIPIZIDE OR GLYBURIDE USERS




PREVALENCE OF OVERLAPPING USE OF THE 5 ANTIMICROBIAL DRUGS ASSOCIATED WITH HYPOGLYCEMIA


INTRODUCTION

STATIN USE IN VERY ELDERLY INDIVIDUALS, 1999-2012.

Johansen ME and Green LA. JAMA Intern Med 2015 Oct; 175: 1715-6

• There is little randomized evidence to guide the use of statins (HMG-CoA reductase inhibitors) in

very elderly individuals (>79 years).

• Despite this, the very elderly have the highest rate of statin use in the United States.

•


STATIN USE IN THE VERY ELDERLY > 79 YRS




DISCUSSION

• One-third of community-dwelling very elderly individuals without vascular disease

reported a statin prescription despite a lack of randomized clinical trials to support their

use

• Despite a lack of clear recommendation for statin use in the primary prevention of the

very elderly within the Adult Treatment Panel III guideline,there was a large increase in

use that coincided with its release.

• Although the medical community has embraced the use of statins for primary prevention

in the very elderly, caution should be exercised given the potential dangers of expanding

marginally effective treatments to untested populations.




GENERAL CONCEPT OF THE IN VIVO BASED PREDICTION OF AUC INCREASES CAUSED BY INHIBITION OF CYP3A4


PHYSICOCHEMICAL AND PHARMACOKINETIC PROPERTIES OF STATINS

RISK FACTORS AND DRUG INTERACTIONS PREDISPOSING TO STATIN-INDUCED

MYOPATHY: IMPLICATIONS FOR RISK ASSESSMENT, PREVENTION AND TREATMENT

Chatzizisis YS et al. Drug Saf 2010 Mar 33 (3): 171-187


STATIN AND DRUG INTERACTIONS BY LIKELY MECHANISM: STATINS METABOLIZED VIA CYP3A4 LIVER AND INTESTINALMETABOLISM (EG, SIMVASTATIN, LOVASTATIN, AND ATORVASTATIN)

EMPHASIZING STATIN SAFETY IN THE HOSPITALIZED PATIENT:A REVIEW

Leung A et al. Am J Med 2012; 125: 845-853




STATIN AND DRUG INTERACTIONS BY LIKELY MECHANISM: STATINS METABOLIZED VIA CYP2C9 (75%), CYP2C8 (5%), AND CYP3A4 (20%) METABOLIZED VIA LIVER AND INTESTINAL METABOLISM (EG, FLUVASTATIN)




STATIN AND DRUG INTERACTIONS BY LIKELY MECHANISM: STATINS METABOLIZED VIA BILIARY SECRETION, INVOLVING HEPATIC DRUG TRANSPORTERS (EG, PRAVASTATIN AND ROSUVASTATIN)




NEW LABEL CHANGES FOR SIMVASTATIN AND LOVASTATIN

• A 78-year-old woman who underwent heart transplantation 11 years earlier, and who

was on a stable everolimus-based calcineurin inhibitor-sparing immunosuppressive regimen,

presented to the emergency department because of fever, cough, and dyspnea.

• Chest x-ray revealed a picture of moderate pneumonia, and the emergency physician

decided to start antimicrobial combination therapy with amoxicillin-clavulanate (1 g every

8 h) and clarithromycin (500 mg every 12 h).

• Afterward, the patient was discharged home.

• Four days later, while on antimicrobial treatment, she presented at the cardiosurgical

department of a different hospital, where she periodically underwent her quarterly post-

transplant follow-up visits.

CASE REPORT

EVEROLIMUS OVEREXPOSURE IN A HEART TRANSPLANT PATIENT RECEIVING CLARITHROMYCIN FOR THE TREATMENT OF PNEUMONIA

Pea F et al. Transpl Infect Dis 2015 Dec; 17: 926–928


TIMELINE OF EVEROLIMUS BLOOD TROUGH CONCENTRATIONS

EVEROLIMUS OVEREXPOSURE IN A HEART TRANSPLANT PATIENT RECEIVING CLARITHROMYCIN FOR THE TREATMENT OF PNEUMONIA

Pea F et al. Transpl Infect Dis 2015 Dec; 17: 926–928


SUMMARY

BENZODIAZEPINE USE AND RISK OF ALZHEIMER’S DISEASE:

CASE-CONTROL STUDY

Billioti de Gage S et al. BMJ 2014 Sep 9 on line published

• 1796 people with a first diagnosis of Alzheimer’s disease and followed up for at least

six years before were matched with 7184 controls on sex, age group, and duration of

follow-up. Both groups were randomly sampled from older people (age >66) living in the

community in 2000-09.

• Benzodiazepine ever use was associated with an increased risk of Alzheimer’s disease

(adjusted OR 1.51, 95% CI 1.36 to 1.69).

• No association was found for a cumulative dose <91 prescribed daily doses.

• The strength of association increased with exposure density

• 1.32 (1.01 to 1.74) for 91-180 prescribed daily doses

• 1.84 (1.62 to 2.08) for >180 prescribed daily doses)

• and with the drug half life

• 1.43 (1.27 to 1.61) for short acting drugs

• 1.70 (1.46 to 1.98) for long acting ones.



• A woman in her 60s with no significant medical history presented to her internist with ear

fullness and asymmetric hearing loss.

• She was referred to an otolaryngologist, who diagnosed idiopathic asymmetric hearing loss.

• Before ordering brain imaging, he prescribed prednisone, 60 mg daily, and valacyclovir for

possible herpes zoster infection.

• He also directed the patient to purchase over-the-counter omeprazole for peptic ulcer

prophylaxis in the setting of steroid use, all medications to be taken for 14 days.

• On day 6 of this regimen, the patient developed subjective fevers and chills and had several

episodes of non bloody emesis and diarrhea.

• She felt better on day 7, with no vomiting or diarrhea.



• On day 8, she developed a red, blotchy, intensely pruritic cutaneous eruption that emerged

simultaneously throughout the body.

• The patient visited her dermatologist that day for the cutaneous eruption, who performed a

biopsy of the skin lesions and instructed her to stop all 3 medications, which she had already

taken that day.

• On the morning of day 9, the patient was taken by ambulance to the hospital, where she was

found to have a temperature of 39°C, a pulse of 102 beats per minute, a respiratory rate of

18 breaths per minute, and dry mucous membranes.

• Her vital signs improved after a few hours on intravenous fluids.

• Physical examination revealed a blanching, macular cutaneous eruption with some papules

involving the trunk and limbs and sparing the palms, soles, and mucous membranes.



• Biopsy test results were consistent with interface and spongiotic dermatitis, suggestive of a

dermatologic drug reaction.

• The distribution of the cutaneous eruption was consistent with the classic dermatologic drug

reaction caused by a proton pump inhibitor (PPI).

• She was treated with hydroxyzine, a topical ointment, and betamethasone.

• Her cutaneous eruption and pruritus improved and she was discharged after a 2-day

hospitalization.


TEACHABLE MOMENT

• The prevalence of PPI use is considerable, with estimated expenditures totaling over $11

billion annually in the United States.

• However, over one-third of PPI prescriptions in the ambulatory setting may not be associated

with an appropriate, documented indication for PPI treatment.

• A recent literature search concluded that systemic corticosteroid therapy rarely causes peptic

ulcers and thus there is no indication for PPI prophylaxis with short-term systemic

corticosteroid use in the absence of concomitant treatment with nonsteroidal antiinflammatory

drugs (NSAIDs).


• Avoiding the prescription of PPIs when it is not medically indicated has the potential to spare

individuals from unnecessary distress, and reduce avoidable hospitalizations and health care

spending.

CONCLUSIONS

PROTON PUMP INHIBITORS AND RISK OF BONE FRACTURESLeontiadis GI and Moayyedi P. Current Treat Opt Gastroenter 2014; 12: 414–423

OPINION STATEMENT

• 34 studies in almost 2 million participants that have reported on the association

between proton pump inhibitor (PPI) therapy and risk of fracture

• There is no clear mechanism through which PPI therapy increases the risk of fracture

• There is insufficient evidence to change PPI prescribing habits based on risk of

fracture

• We only recommend prescribing PPI therapy when there is a clear indication that

benefit will outweigh risk and at the lowest effective dose.

• Patients should be regularly assessed as to whether acid suppression is still required


ASSOCIATION OF PROTON PUMP INHIBITORS WITH RISK OF DEMENTIA

A PHARMACOEPIDEMIOLOGICAL CLAIMS DATA ANALYSISGomm W et al. JAMA Neurol. 2016 Apr 1; 73(4): 410-6

STUDY DESIGN

• OBJECTIVE: To examine the association between the use of PPIs and the risk of incident

dementia in the elderly.

• DESIGN: Prospective cohort study data from 2004 to 2011, derived from the largest German

statutory health insurer, Allgemeine Ortskrankenkassen (AOK).

• MAIN OUTCOMES: Diagnosis of incident dementia and association with PPI use analyzed by means

of time-dependent Cox regression.

• The model was adjusted for potential confounding factors, including age, sex, comorbidities, and

polypharmacy.




FLOWCHART OF PATIENTS INCLUDED FOR ANALYSIS




CHARACTERISTICS OF PROTON PUMP INHIBITOR (PPI) USERS AND NONUSERS FOR COX REGRESSION WITH TIME-DEPENDENT COVARIATES




DATA ON RISK OF INCIDENT DEMENTIA BY PPI USE




DEMENTIA-FREE SURVIVAL BY USE OF PPIs




DATA ON RISK OF INCIDENT DEMENTIA BY PPI USE, AGE-GROUP ANALYSIS




CONCLUSIONS AND RELEVANCE

• The avoidance of PPI medication may prevent the development of dementia

• This finding is supported by recent pharmacoepidemiological analyses on primary data

and is in line with mouse models in which the use of PPIs increased the levels of β-

amyloid in the brains of mice

• Randomized, prospective clinical trials are needed to examine this connection in more

detail

INTERAZIONE TRA FARMACI: CASI CLINICI A CONFRONTO · STATIN USE IN VERY ELDERLY INDIVIDUALS,...

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