GI Meds Treatment of Irritable Bowel Syndrome PDF

GI MEDS T R E AT M E N T O F I R R I TA B L E B O W E L SYNDROME Debra Forzese, Pharm. D. I R R I TA B L E B O W E L SY N D R O M E ( I B S ) IBS is a chronic GI disorder Treatment focus is on symptom suppression with only a few drugs found to be efficacious over the long term IBS Predominant bowel...

GI MEDS T R E AT M E N T O F I R R I TA B L E B O W E L SYNDROME Debra Forzese, Pharm. D. I R R I TA B L E B O W E L SY N D R O M E ( I B S ) IBS is a chronic GI disorder Treatment focus is on symptom suppression with only a few drugs found to be efficacious over the long term IBS Predominant bowel symptom leads to IBS classification o IBS with constipation (IBS-C) o IBS with diarrhea (IBS-D) o IBS with mixed constipation/diarrhea (IBS-M) A N T I - S PA S M OT I C D R U G S 5/17/23 Sample Footer Text 4 A N T I S PA S M OT I C S Dicyclomine Hyoscamine (Scopolamine) A N T I - S PA S M OT I C S Used for IBS for decades The goal of these drugs is to reduce symptoms by increasing colonic transit time, improving stool consistency, and reducing stool frequency Anti-spasmotics have favorable side effect profile combined with positive effects A N T I - S PA S M OT I C S Effective in treating wide range of IBS symptoms o Diarrhea o Constipation o Abdominal pain o Bloating A N T I - S PA S M OT I C S One of most frequently used treatments for IBS Assessing efficacy on global IBS symptoms is difficult since multiple agents with different MOA Antispasmotics relax intestinal smooth muscle and reduce GI motility Anticholinergic side effects – constipation, dry mouth, blurred vision, confusion (elderly), tachycardia, hyperthermia, narrow angle glaucoma, urinary retention A N T I - S PA S M OT I C S Relax intestinal smooth muscle causing reduction in GI motility Decrease fecal urgency and pain Used in patients with IBS-D Limited data support their use – different opinions on whether they are beneficial S E R ATO N I N 5 - H T- 3 R E C E P TO R A N TA G O N I S T S 5/17/23 Sample Footer Text 10 S E R ATO N I N 5 - H T- 3 R E C E P TO R A N TA G O N I S TS 5-HT modulates visceral sensation and motility Seratonin 5-HT-3 receptor antagonists work by slowing intestinal transit S E R ATO N I N 5 - H T- 3 R E C E P TO R A N TA G O N I S TS ALOSETRON Alosetron – works by slowing intestinal transit to allow for more water reabsorption resulting in more formed stool Safety concerns led to alosetron being taken off market in 2000 Reports of ischemic colitis, complicated constipation (obstruction or perforation), and death Alosetron reintroduced under a risk evaluation and mitigation strategy (REMS) in 2002 ALOSETRON Blocking of 5-HT receptors in patients with IBS-D reduces pain, abdominal discomfort, urgency, and diarrhea Also decreases visceral hypersensitivity by reducing blood flow to emotional centers in the brain Taken orally If constipation occurs patients stop alosetron until resolved, if symptoms recur at lower dose alosetron should be discontinued ALOSETRON No dose adjustment in renal or hepatic impairment Pregnancy – category B Breastfeeding – unknown if transfers to breast milk, consider risk versus benefit of breastfeeding infant while mother on alosetron, risk of infant exposure, treatment benefits to mother ALOSETRON Adverse effects Constipation – most common Nausea, intestinal discomfort and pain, abdominal distention Hemorrhoids Headache, tiredness A LOS E T RO N – C O N T R A I N D I CAT I O N S Chronic/severe constipation Intestinal obstruction Diverticulitis Crohn disease or ulcerative colitis Severe hepatic impairment History of blood clots Concomitant use of fluvoxamine (strong inhibitor CYP1A2) – increased blood levels ALOSETRON Use limited to women experiencing chronic (>6 months), severe IBS-D symptoms who lacked response to traditional therapies Initial safety concerns lessened due to low incidence of ischemic colitis and reduced rates of complicated constipation, possibly attributed to restricted prescribing doses established by the REMS ALOSETRON Current evidence supports use of alosetron to relieve symptoms of women with severe IBS-D when other interventions failed Studies of other agents in this class including ondansetron are ongoing to evaluate safety and efficacy of this agent in patients with IBS-D CHLORIDE CHANNEL A C T I VATO R S 5/17/23 Sample Footer Text 19 C H L O R I D E C H A N N E L A C T I VATO R Lubiprostone (Amitiza) G UA N Y L AT E C Y C L A S E - C AGONISTS 5/17/23 Sample Footer Text 21 G UA N Y L AT E C Y C L A S E - C AG O N I S TS Linaclotide (Linzess) Plecanatide (Trulance) G UA N Y L AT E C Y C L A S E AC T I VATO R S Target guanylate cyclase-C receptors in intestinal epithelial cells Increase intestinal fluid secretion and peristalsis and reduce activation of visceral nociceptive neurons Improvement develops quickly and response is maintained over time Considered secretagogues Well tolerated, most common adverse effect is diarrhea, sometimes severe LINACLOTIDE FDA indications o IBS-C o Chronic idiopathic constipation Use in adults only Reserve for patients with persistent constipation despite osmotic laxative use LINACLOTIDE No dose adjustment in kidney or hepatic impairment Adverse effects o Diarrhea – sometimes severe o Abdominal pain o Headache LINACLOTIDE- US BOXED WARNING Risk of serious dehydration in pediatric patients younger than 2 years Linaclotide is contraindicated in pediatric patients younger than 2 years in nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. LINACLOTIDE Warnings o Some reports of severe diarrhea associated with dizziness, syncope, hypotension, and electrolyte abnormalities requiring IV fluids and/or hospitalization Drug Interactions – no significant drug interactions known LINACLOTIDE Pregnancy – limited data, other agents preferred Breastfeeding – not present in breastmilk, according to manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. SODIUM/HYDROGEN EXCHANGER 3 (NHE3) IN HIBITOR 5/17/23 Sample Footer Text 29 NHE3 INHIBITOR Tenapanor (Ibsrela) T E N A PA N O R Approved by FDA for treatment of IBS-C for use in IBS-C in adults only Inhibits sodium/hydrogen exchanger isoform 3 found on the surface of the small intestine and the colon Blocks absorption of dietary sodium resulting in increased water secretion, which causes more frequent and softer bowel movements Decreases visceral hypersensitivity which leads to reduced abdominal pain T E N A PA N O R – U S B OX E D WA R N I N G Contraindicated in patients