Gastroesophageal reflux disease
Condition in which reflux of gastric contents into the esophagus causes troublesome symptoms (heartburn, regurgitation) and/or esophageal mucosal injury.
ICD-10 K2114 drugs
Also known as: GERD, GORD, Acid reflux, Reflux esophagitis
Drugs used for this condition
- AEsomeprazoleFirst line · Drugs for peptic ulcer and GORD. Proton pump inhibitorsFirst-line therapy for GERD in adults and adolescents. NICE CG184 (2014, updated 2019) and ACG 2022 recommend PPIs as the baseline GERD therapy, with dose chosen by esophagitis severity. Erosive esophagitis is treated for 8 weeks, non-erosive disease for 4 weeks with reassessment. Esomeprazole shows efficacy comparable to other PPIs at equivalent doses; at 40 mg it outperforms omeprazole 20 mg in healing of severe erosive esophagitis.
- ALansoprazoleFirst line · Proton pump inhibitor (PPI)First-line for gastroesophageal reflux disease per ACG 2022 and Spanish AEG 2024 alongside other PPIs. Standard dose 30 mg once daily for 4–8 weeks. In erosive esophagitis, extend to 8 weeks with possible step-down to maintenance 15 mg. The 2019 Cochrane meta-analysis showed comparable efficacy across PPIs; differences are in cost and individual tolerability.
- AOmeprazoleFirst line · Proton pump inhibitorsPPIs are first-line for GERD in adults per ACG 2022 and NICE CG184. Standard dose: omeprazole 20 mg once daily for 4–8 weeks in non-erosive disease, 40 mg in erosive disease. If the response is inadequate, assess adherence, timing, functional heartburn, and alternative diagnoses. Long-term maintenance uses the lowest effective dose.
- APantoprazoleFirst line · Proton pump inhibitorsFirst-line GERD therapy. PPIs are the most effective agents for acid suppression. Pantoprazole 40 mg once daily 30 minutes before breakfast. Course 4–8 weeks, then attempt dose reduction or on-demand dosing.
- ARabeprazoleFirst line · Proton pump inhibitor (PPI)First-line for GERD per ACG 2022 and the Spanish AEG 2024. Dose 20 mg once daily for 4–8 weeks. Compared with omeprazole, more convenient in patients on clopidogrel and CYP2C19 rapid metabolizers. Efficacy across PPIs is comparable per the 2019 Cochrane meta-analysis.
- BFamotidineSecond line · H2-histamine receptor antagonistAlternative to proton pump inhibitors in mild-to-moderate GERD when PPIs are intolerable, or for nocturnal acid breakthrough as PPI add-on. Dose 20–40 mg twice daily. Less effective than PPIs – omeprazole and esomeprazole suppress acid 80–95% over 24 hours versus 70% with famotidine. Used for episodic symptoms or nocturnal acidity.
- BSodium alginateFirst line · Anti-reflux agent forming a protective raftAlginate relieves heartburn and acid regurgitation by mechanically closing the exit from the stomach into the esophagus. The meta-analysis by Leiman and colleagues (Dis Esophagus 2017) pooled randomized trials and showed that alginates relieve reflux symptoms better than placebo and antacids, although they fall short of proton pump inhibitors. The AEMPS ficha técnica gives the indication as symptomatic treatment of heartburn and acid reflux in adults and adolescents from 12 years: 2 to 4 tablets after meals and at bedtime, up to 4 times a day. NICE guideline CG184 places alginates in the same niche – fast symptomatic relief rather than baseline treatment of reflux disease. If symptoms persist beyond 7 days, the ficha asks for reassessment. The calcium limit matters: prolonged high doses cause hypercalcemia and kidney stones.
- CAlmagateAdd-on therapy · Antacid (aluminium magnesium hydroxide carbonate)Symptomatic relief in moderate heartburn and acid reflux. ACG 2022 and the Spanish AEG GERD guideline (2022) set proton pump inhibitors (omeprazole, pantoprazole, esomeprazole) and lifestyle change as first-line in GERD. Antacids including almagate are quick symptomatic relief used before or together with a PPI, especially in episodic heartburn. Not used as monotherapy in erosive esophagitis. Antacids reduce absorption of some drugs (fluoroquinolones, tetracyclines, levothyroxine, iron) – separate doses by about 2 hours; use with caution in renal impairment due to aluminum and magnesium accumulation.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DCinitaprideNot recommended · Benzamide prokinetic with combined serotonin and dopamine receptor activityProkinetics are not first-line in GERD. Cinitapride may be added to a proton-pump inhibitor for persistent motility-related symptoms (belching, postprandial nausea), but the benefit is limited and does not exceed PPI dose optimization.
- DCisaprideNot recommended · Prokinetic, 5-HT4 serotonin receptor agonist (withdrawn EU/US)Cisapride was historically used for gastroesophageal reflux disease and gastroparesis to enhance GI motility. FDA withdrew it in 2000 after reported torsades de pointes and sudden cardiac death, especially with CYP3A4 inhibitors. Not available in Spain. Card retained for historical reference and recognition of dangerous combinations in countries where the drug is still accessible.
- DLicorice root (Glycyrrhiza glabra, root and rhizome; including deglycyrrhizinated DGL)Not recommended · Root of Glycyrrhiza glabra and related Glycyrrhiza uralensis and Glycyrrhiza inflata species. Supplements come as root extract, candy, tea, alcoholic tincture, and deglycyrrhizinated form (DGL, without glycyrrhizin). Marketing promotes licorice as «adrenal support», a remedy for «adrenal fatigue», and a «natural remedy for viruses and gastritis». EMA HMPC published a European herbal monograph (2013) with traditional uses in cough, dyspepsia, and skin irritation; AEMPS does not register it as a medicine; AESAN classifies it as a complemento alimenticio. FDA grants GRAS status as a food additive but in 2017 warned consumers of cardiac arrhythmia risk with intake above 56 g/day of black licorice candy in people over 40.Deglycyrrhizinated licorice (DGL) is actively marketed for heartburn, gastritis, reflux, and ulcer as a «natural PPI alternative». The Raveendra 2012 RCT (Evid Based Complement Alternat Med) in 50 patients with functional dyspepsia reported lower CGSRS symptom scores after 30 days of GutGard licorice root extract 150 mg/day. The sample is small, manufacturer-sponsored, without comparison to omeprazole or rebamipide. Older 1970-80s work on carbenoxolone (a semisynthetic glycyrrhetinic acid derivative) showed gastric ulcer healing, but carbenoxolone was withdrawn from most markets owing to mineralocorticoid side effects. NICE NG184 for gastro-oesophageal reflux disease recommends proton pump inhibitors (omeprazole, esomeprazole, pantoprazole, rabeprazole, lansoprazole) and H2 blockers (famotidine, nizatidine) as first-line, with alginates (Gaviscon) and antacids for symptom relief. The Spanish SEPD follows the same approach. Licorice is absent from reflux and peptic ulcer guidelines. DGL stripped of glycyrrhizin carries less hypertension risk and less benefit. If licorice was offered in place of a PPI, consider seeking a second opinion – alarm features (weight loss, dysphagia, melaena, haematemesis, anaemia) require gastroscopy, not self-treatment with licorice.
- DSimeticoneNot recommended · Drugs for functional bowel disorders. Antifoaming agentsSimethicone is an anti-foaming agent that lowers the surface tension of gas bubbles in the gut, and it is sometimes offered for GERD, reflux and heartburn. For this use the benefit has not been shown: there is no convincing evidence that simethicone reduces reflux or heals the esophagus. GERD responds to other measures – proton pump inhibitors, changes in diet and lifestyle, and a medical check-up when needed. The substance itself is harmless in this role, but it should not be used instead of treatment with proven benefit, or the right therapy may be missed.
- DSodium bicarbonateNot recommended · Systemic alkalinizing agent, antacidA spoon of baking soda in a glass of water is the best known home remedy for heartburn, and it works exactly once. In reflux disease soda is unsuitable as ongoing treatment. Acid neutralization lasts minutes, then the stomach answers with a new release – the AEMPS ficha técnica lists the rebound effect among adverse reactions. Sodium from soda retains water, and for people with hypertension and heart failure that costs more than the heartburn did. NICE guideline CG184 builds reflux management differently: a course of a proton pump inhibitor, assessment of alarm symptoms, gastroscopy where needed, with antacids and alginates on top for fast relief. If soda or effervescent bicarbonate is advised daily for heartburn, consider seeking a second opinion.
- FBetaine hydrochlorideNot recommended · Over-the-counter supplement, an acidic salt of betaine (trimethylglycine hydrochloride); marketed as a gastric acid replacement for «low stomach acid»; commonly combined with pepsin on iHerb and AmazonIn GERD, betaine hydrochloride is CONTRAINDICATED. Betaine HCl briefly lowers gastric pH – exactly what aggravates reflux into the esophagus and worsens erosive esophagitis. The marketing idea «heartburn from low acid, add acid» contradicts physiology: in GERD, heartburn arises from acid content reflux into the esophagus and lower esophageal sphincter weakness, not from a hydrochloric acid deficit. ACG 2022 and NICE CG184 unambiguously recommend proton pump inhibitors (omeprazole, esomeprazole, pantoprazole) for GERD for 4–8 weeks with step-down. Betaine HCl is not mentioned as an option in these guidelines – the product is potentially harmful in an acid-related disease. If betaine HCl was bought «for heartburn», stop it immediately and discuss heartburn with a gastroenterologist or family doctor – confirmed GERD needs PPIs, not acidifiers.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit