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DRUGS FOR IBS-DIARRHEA &

PPI THERAPY

IBS - DIARRHEAIrritable Bowel Syndrome (IBS)

a chronic functional disorder of the gastrointestinal tract characterized by

chronic abdominal pain and altered bowel habits in the absence of alarm symptoms

IBS - DIARRHEA ROME IV CRITERIA Recurrent ABD pain

on average at least 1 day a week, in the last 3 months, associated with 2

or more of the following:

S/S started at least 6 months ago

Related to defecation

a/w change in frequency

a/w change in consistency

(based on Bristol Scale)

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IBS – DIARRHEA Management Education & Reassurance

Dietary Modifications i.e FODMAP diet Gluten avoidance Physical activity

Adjunctive Pharmacologic Therapy

Eluxadoline (Viberzi)

Mixed Mu –opioid receptor agonist,

Delta opioid receptor antagonist &Kappa opioid receptor agonist** Controlled Substance – IV**

Eluxadoline (Viberzi)Mechanism of Action

Reduces peristalsis and acts to decrease ABD pain in IBS-D without constipation side effects

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Eluxadoline (Viberzi)PHARMACODYNAMICS

Protein Binding Metabolism via

CYP450 Pathway

PHARMACOKINECTICS

Peak in 1.5 hours with food and 2 hours without

Half life 3.7 – 6 hours

Excreted feces

Eluxadoline (Viberzi)DOSING

Oral dosing: 100 mg BID in pts with a Gallbladder 75 mg BID without Given with food NO dose adjustment for Renal Disease Child-Pugh class A & B use 75 mg BID Child –Pugh class C DO NOT USE

Eluxadoline (Viberzi)SIDE EFFECTS

Dizziness, Fatigue, Skin Rash,

Increased AST and ALT

N/V, ABD pain

Contraindications Blockage in

gallbladder or Sphincter of Oddidysfunction

ETOH Abuse Hx of Pancreatitis Severe liver

problems Pregnancy/Lactation

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Eluxadoline (Viberzi) DRUG INTERACTIONS

Analgesics & Anticholinergics: may increase constipating effects

Decrease dose to 75 mg BID in combination with:

Hep C drugs, HIV meds, Cyclosporine, Gemfibrozil and Rifampin

IBS – DIARRHEARifaximin (Xifaxan)

Rifaximin (Xifaxan) Mechanism of Action

Non systemically absorbed antibiotics. Approved in 2015

Inhibits of protein synthesis and growth of bacteria

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Rifaximin (Xifaxan)PHARMACODYNAMICS

Binds to Protein

Metabolized mainly by CYP3A

PHARMACOKINECTICS

Half Life elimination in 6 hours

Time to peak ~1 hr Primarily excreted

in feces

Rifaximin (Xifaxan) DOSING

550 mg PO TID x 2 weeks

Recurrence of s/s can be retreated up to 2 times with same dosing regimen

Can be given with or without food

Renal = no dose adjustments

Hepatic= no dose adjustments; use with caution in Child Pugh class C

Rifaximin (Xifaxan) 3 trials showed that Xifaxan 550 mg relieves

multiple symptoms commonly associated with IBS-D.1 After a single course (ie, 2-week treatment) with

Xifaxan 550 mg TID in Trial 1 and Trial 2, patients experienced relief of IBS-D symptoms, i.e abdominal pain, and stool consistency, and

effects sustained for an average of 3 months. In Trial 3, repeat treatment with Xifaxan 550 mg

was effective when symptoms recurred.

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Rifaximin (Xifaxan)Side Effects/Contraindications Main side effects are Nausea and Elevated ALT

XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN.

Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.

Do NOT use in pregnancy

IBS - DIARRHEAXifaxan 550 TID x 2 wk Viberzi 75/100 mg BID

PPI THERAPY

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PPI - OBJECTIVES Data to support use of PPI

Examine features of 3 specific PPI drugs

Identify appropriate Patients for PPI in clinical practice

PPI MECHANISM OF ACTION

Final step is known as H-K-ATPaseofacid secretion.

PPIs inhibit only active parietal cells

ALL are the similar in action;

DIFFER in pharmacokinetic properties i.e.

pKa, bioavailability, peak plasma levels and route of excretion

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PPI - PHARMACOKINETICSDexlansoprazole Esomeprazole Pantoprazole

Time to Peak 1st peak 1-2 hrs2nd peak 4-5 hrs

1- 1.6 hours 2 - 2.5 hours

Metabolism& Clearance

Metabolized by LiverExcreted in urine and feces

SAME Same + via Bile

pH Increase N/A 4.0 3.9

PHARMACOKINETICSDIFFERENCES

DEXILANT (DEXLANSOPRAZOLE)• Can be given AC or PC• Dual Peak pattern• Inhibits CYP2C19 Pathway• Metabolized by CYP3A4

Nexium (ESOMEPRAZOLE)• NO adjustment for renal

patients• Absorption reduced if

taken with food• IV Formulation• Metabolized by CYP2C19

Pathway; increased risk of drug interaction

Protonix(PANTOPRAZOLE)• Highest plasma

concentration levels • IV formulation• Used in combination with

ADR inhibitors • 2 step Metabolism pathway

has lowest potential for drug interaction

WHO NEEDS A PPI ??

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INDICATIONS FOR PPI USE Eradication of H- pylori GERD/ Esophagitis/ Gastritis Peptic Ulcer Disease Treatment & Prevention of Gastric Ulcer

associated with NSAIDS Maintenance Therapy Zollinger-Ellison Syndrome

PPI D

OSING

Dexlansoprazole Esomeprazole PantoprazoleH Pylori Rx 30 mg PO BID 10-14

days40 mg PO daily 10-

14 days40 mg PO BID 10-14 days

GERD 30 mg PO daily x 4 weeks

20 mg daily 4-8 weeks

40 mg once daily for up to 8 weeks; can repeat

Non Erosive Gastritis

30 mg PO daily x 4 weeks

20 mg daily 4-8 weeks

NONE

Erosive Esophagitis 60 mg PO daily up to 8wks

20-40 mg daily x 4 – 6 weeks or IV x 10 days

IV: 40 mg once daily for 7 to 10 days

Maintenance Therapy

Not labeled indication

20 mg PO daily 40 mg once daily

NSAID induced Gastric Ulcer Prophylaxis

& treatment of Ulcers due to

NSAIDS

NONE 20-40 mg daily 6 months

Prophylaxis dosing label not in U.S.

GU/DU Re- bleeding after

Endoscopy

NONE 80 mg bolus then 8 mg/hr x 72 hours; then 40 mg PO

80 mg bolus then 8 mg/hr x 72 hours; then 40 mg PO

Zollinger-Ellison Syndrome

NONE 40 mg twice daily Oral: Initial: 40 mg twice daily IV: 80 mg every 12 hours ; adjusted

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PPI – Side EffectsCommon things are….

Uncommon thingscan occur….

PPI-Medication Safety Issues Infections

Malabsorption

Atrophic Gastritis

Dementia & Kidney Disease

Drug Interactions

PPI-Medication Safety Issues Infections: C-diff, Pneumonia (CAP &

HCAP) Malabsorption: Mg, Ca (decreasing bone

density)leading to Fractures of hip, wrist, & spine

Decreased in Vit B12 absorption & Hypergastrinemia (seen with Omeprazole use)

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PPI-Medication Safety Issues Atrophic Gastritis: risk is small

Dementia and Kidney Disease:studies ongoing…

Drug Interactions:May interfere with drugs that need high pHIncreases levels of INR in patients on Coumadin, increase levels of patients on Tacrolimus and Methotrexate

PPI-Medication Taper WHY

To avoid rebound gastric acid hyersecretion

WHEN: Pt’s with GERD or Dyspepsia start after

asymptomatic x 3 months NO taper need s/p treatment for GU/DU Higher dose 40mg daily – BIB; dose reduce

by 50% every week