This site is intended for Healthcare Professionals only

Treating indigestion with ranitidine and PPIs

Medicines bookmark icon off

Treating indigestion with ranitidine and PPIs

Alan Nathan discusses non-antacid OTC indigestion treatments

Ranitidine is the only H2-receptor antagonist currently marketed for OTC sale in the UK. Famotidine and nizatidine are both licensed for sale without prescription for similar indications to ranitidine but no products are available.

How does it act?

Histamine is thought to be the most important mediator of gastric acid secretion through its activation of parietal cell receptors in the stomach lining. It stimulates the production of a protein kinase, which activates the proton pump (the enzyme hydrogen/potassium adenosine triphosphatase, or H+/K+ ATPase) in parietal cells to secrete hydrogen ions into the stomach. H2-receptor antagonists interfere with this mechanism by occupying receptor sites on the parietal cells, blocking the action of histamine.

They are effective for longer than antacids because their action is not limited by contact time with the stomach contents. Ranitidine reaches peak plasma levels about an hour after ingestion and the elimination half-life is two to three hours. Acid secretion is inhibited for up to 12 hours.

Licensed indications

Ranitidine is licensed for the symptomatic relief of heartburn, indigestion and acid indigestion, and also for prevention of indigestion and heartburn associated with food and drink consumption.

Cautions and contraindications

Ranitidine is well tolerated and the incidence of side effects is low. It should not be sold to patients taking non-steroidal anti-inflammatory drugs, as it may mask the symptoms of developing peptic ulcer. Pregnant or breastfeeding women are advised to consult their doctor before taking ranitidine.

Interactions

Ranitidine can interfere with the metabolism and elimination of drugs through the cytochrome P450 (CYP) enzyme pathway. However, the manufacturer states that at usual therapeutic doses ranitidine does not potentiate the action of drugs such as midazolam, metoprolol, phenytoin and theophylline, which are among those that theoretically could be subject to this interaction.

Close monitoring of prothrombin time of patients on warfarin and other coumarin anticoagulants is recommended, because of the drugs’ narrow therapeutic index. The activity of drugs that require an acid medium for absorption may be reduced by ranitidine, including ketoconazole and itraconazole.

OTC dosages

Ranitidine 75mg tablets are licensed as both P and GSL medicines, with different dosage schedules.

  • For the P product: For adults and children aged 16 years and over, one tablet as soon as symptoms occur. If symptoms persist for more than an hour or return, another tablet can be taken, to a maximum of four tablets in 24 hours. For prevention of symptoms associated with consuming food and drink, one tablet should be taken half to one hour in advance. Dosage should not be continued for more than two weeks continuously, and patients should be referred to their doctor if symptoms worsen or persist beyond this period.
  • For the GSL product: As above, but a maximum of two tablets in 24 hours and for no more than six days without consulting a pharmacist or doctor.

How effective is OTC ranitidine?

There is very little published evidence regarding the efficacy of ranitidine for its OTC licensed indications. Such trials and reviews as have been published indicate that it is effective.1,2,3

 

PANTOPRAZOLE AND ESOMEPRAZOLE

How do they act?

Proton pump inhibitors (PPIs) such as pantoprazole and esomeprazole directly inhibit the parietal cells’ proton pump and thereby block the secretion of gastric acid. PPIs have a more prolonged effect on acid suppression than H2-antagonists, although onset of action may take longer.

PPIs have a more prolonged effect on acid suppression than H2-antagonists, although onset of action may take longer

What are they licensed for?

Gastric reflux, the symptoms of which are heartburn and acid regurgitation, is a chronic, intermittent, relapsing disorder of varying frequency and severity. Although there is usually no underlying pathology, sufferers can experience recurrent attacks, including at night, which can be distressing and negatively affect quality of life.

Pantoprazole and esomeprazole are indicated for the short-term treatment of reflux symptoms, in adults aged 18 years and over. Omeprazole is also licensed for OTC sale and a product was available, but has been discontinued.

Cautions and contraindications

Patients should not take OTC pantoprazole or esomeprazole and should consult a doctor, if they:

  • Have any symptoms that may indicate a gastric ulcer or malignancy, as treatment with the drugs may alleviate symptoms and delay diagnosis
  • Have had previous gastric ulcer or gastrointestinal surgery
  • Have been on continuous symptomatic treatment for indigestion or heartburn for four or more weeks
  • Have jaundice or severe liver disease
  • Are aged over 55 years with new or recently changed symptoms.

Patients should not take another proton pump inhibitor or H2 antagonist concomitantly. OTC pantoprazole or esomeprazole are not recommended for pregnant or breastfeeding women.

Interactions

Pantoprazole and esomeprazole are metabolised in the liver via the cytochrome P450 enzyme system. But they can be given with most drugs, as no clinically significant interactions have been observed. However, they may reduce the absorption of active substances whose bioavailability is dependent on gastric pH, eg, ketoconazole and atazanavir. And they may possibly enhance the anticoagulant effect of coumarins, so monitoring of prothrombin time/INR is recommended if co-administered.

OTC dosages

For both pantoprazole and esomeprazole, one 20 mg tablet per day, for up to two to three consecutive days if necessary to achieve improvement of symptoms. Once complete relief of symptoms has occurred, treatment should be discontinued. If no symptom relief is obtained within two weeks of continuous treatment, the patient should consult a doctor.

Legal classification

Pantoprazole is a P medicine. Esomeprazole was originally authorised as a non-prescription medicine through the European Union’s centralised procedure. The UK manufacturer subsequently applied for and was granted GSL status.

How effective are they?

Three trials have found on-demand therapy with either pantoprazole 20mg or esomeprazole 20mg to be a comparably effective treatment strategy for the treatment of mild reflux.4,5,6

REFERENCES

  1. Redstone HA, Barrowman N, Veldhuyzen Van Zanten SJ. H2-receptor antagonists in the treatment of functional (non-ulcer) dyspepsia: a meta-analysis of randomized controlled clinical trials. Aliment Pharmacol Ther. 2001;15:1291-9.
  2. Farup PG, Wetterhus S, Osnes M, Ulshagen K. Ranitidine effectively relieves symptoms in a subset of patients with functional dyspepsia. Scand J Gastroenterol.1997;32:755-9.
  3. Farup PG, Larsen S, Ulshagen K, Osnes M. Ranitidine for non-ulcer dyspepsia. A clinical study of the symptomatic effect of ranitidine and a classification and characterization of the responders to treatment. Scand JGastroenterol.1991;26:1209-16.
  4. Kalaitzakis E, Björnsson E. A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD). Ther Clin Risk Manag. 2007;3:653-63.
  5. Scholten T, Teutsch I, Bohuschke M, Gatz G. Pantoprazole on-demand effectively treats symptoms in patients with gastro-oesophageal reflux disease. Clin Drug Investig. 2007;27:287-96.
  6. Goh KL, Benamouzig R, Sander P, Schwan T. Efficacy of pantoprazole 20mg daily compared with esomeprazole 20mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial – the EMANCIPATE study. Eur J Gastroenterol Hepatol. 2007;19:205-11.
Copy Link copy link button

Medicines

Share: