Pharmacological Therapy for Gastrointestinal Manifestations in SSc (Courtesy of Monika Lammi, rights reserved)

Drug Class	Drug Name	Concerns for use/Comments
GERD
Proton Pump Inhibitors	Pantoprazole* Omeprazole* Lansoprazole* Esomeprazole* Rabeprazole* Dexlansoprazole	*Bioavailability reduced if taken with food Take 30–60 min before breakfast. Decreased absorption of: Mg, B12, Fe Risks (prolonged use): renal insufficiency, osteoporosis, atypical fractures, pneumonia, and dementia.
Histamine 2 Antagonists	Famotidine Cimetidine	Possible inhibition of cytochrome P450 with possible enhanced effects of drugs with P450 reliant metabolism
Antiacids	Calcium carbonate	Hyperkalemia, alkalosis and acute or chronic renal injury.
	Aluminum hydroxide	Aluminum retention with neurotoxicity and anemia in renal failure. Hypophosphatemia.
Surface agents	Gaviscon +/− alginate
	Sucralfate	Can bind to other drugs if taken simultaneously. Hypophosphatemia. Combining with antiacids can amplify these side effects.
Promotility/LES	Metoclopramide	May increase gastric motility in patients with systemic sclerosis. FDA advised against use for more than 3 months SE: traditive dyskinesia, cardiac arrythmia (monitor with EKG)
	Domperidone	Not FDA approved in US. Can be obtained with Investigational New Drug Application. SE: cardiac arrhythmia
	Buspirone	Increases the lower esophageal sphincter pressure, amplitude of esophageal contractions. Appears more effective for GERD-related symptoms not esophageal hypomotility symptoms (dysphagia and chest pain).
	Baclofen	Shown to augment lower esophageal sphincter pressure in patients with GERD. Not studied in patients with SSc.
Gastroparesis
Promotility agents	Metoclopramide	May increase gastric motility in patients with systemic sclerosis FDA advised against use for more than 3 months Risk: traditive dyskinesia, cardiac arrythmia (monitor with EKG) FDA advised against use for more than 3 months
	Domperidone	Not FDA approved in US. Can be obtained with Investigational New Drug Application. SE: cardiac arrhythmia (monitor with EKG)
	Erythromycin	Not recommended long term: tachyphylaxis, may cause small bowel dysmotility. SE: cardiac arrhythmia (monitor with EKG)
	Prucalopride	Improves gastric, small bowel and colonic transit. FDA approved for constipation.
	Cisapride	Improves postprandial symptoms and gastric emptying. More potent acutely than metoclopramide. Withdrawn from the US market because of cardiac arrhythmia.
Antiemetics	Ondansetron	SE: Prolongs GI transit, headache, cardiac arrhythmia.
	Granisetron	SE: constipation, headache, cardiac arrhythmias
	Prochlorperazine	SE: Sedation, tardive dyskinesia
	Promethazine	SE: Central, cardiac arrhythmia
Dyspepsia
Neuromodulators	Buspirone	Improves gastric accommodation and symptoms of dyspepsia, but decreases gastric emptying of liquids.
	Mirtazapine	Improves dyspepsia, sleep, depression SE: weight gain, drowsiness
Herbal	FDgard (caraway oil and I-menthol)
SIBO
Antibiotics	Rifaximin Metronidazole Amoxicillin/clavulanic acid Norfloxacin	Treat for 2 weeks. High risk of recurrence due to small bowel dysmotility. Cycle regimens to limit antibiotic resistance. May consider use of prokinetics, see below. Antibiotics, e.g. fluoroquinolones may contribute to clostridium difficile overgrowth
Chronic Intestinal pseudo-obstruction
Prokinetics	Metoclopramide Erythromycin Prucalopride	See above. May also be considered for SIBO.
Cholinesterase inhibitor	Pyridostigmine	SE: bradycardia, excessive bronchial secretions, cholinergic crisis
Somatostatin analog	Octreotide	Used in patients who failed to respond to other prokinetic agents. Inhibits gastric motility.
Constipation
Bulk forming laxatives	Psyllium Methylcellulose	Patients with gastric dysmotility and visceral hypersensitivity may not be able to tolerate.
Osmotic laxatives	Polyethylene glycol	SE: abdominal pain, distention, bloating.
Stimulant laxatives	Bisacodyl Glycerol
Guanylate cyclase-C receptor agonists	Linaclotide	Diarrhea, bloating.
	Plecanatide	Improves gastric, small bowel and colonic transit. Diarrhea.
Chloride channel activator	Lubiprostone	Nausea, diarrhea.
Promotility agent	Prucalopride	Improves gastric, small bowel and colonic transit. FDA approved for constipation.