Histamine H2-Receptor Antagonists (H2RA)


 

Cimetidine, Famotidine, Nizatidine, Ranitidine

  Issues for Surgery


For regular, chronic use – risk of rebound hyperacidity if omitted.

Increased risk of acid aspiration and/or post-operative stress-related mucosal disease if omitted.

For investigations of Helicobacter pylori (H. pylori) associated dyspepsia – risk of false negative if continued.


  Advice in the Perioperative period



Elective and Emergency Surgery

Continue.

Patients who take ‘when required’ H2RA should be advised to take a dose of their usual medication the evening prior to and/or on the morning of surgery.

EXCEPT:

  • Investigations for H. pylori – stop 2 weeks prior to investigation1.

For patients with increased risk factors for aspiration (e.g. pregnancy, obesity, non-fasted state in emergency surgery) consider administration of acid-suppressing medication (oral or intravenous) pre-operatively – see Further Information ‘H2RAs vs. Proton Pump Inhibitors (PPIs)’. Please refer to specific product information on the dose(s) of H2RA to be administered pre-operatively.

Post-operative Advice

Patients undergoing Anti-Reflux Surgery or Total Gastrectomy

If patient is on H2RA, consider continued need for H2RA therapy following surgery.

Use of Post-operative Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Consider prophylaxis with a H2RA, if PPI not suitable, for patients commenced on NSAIDs for post-operative pain relief, especially in those that have increased risk factors for gastro-intestinal ulceration. Use the lowest possible dose. Discontinue H2RA treatment as soon as patient stops NSAID treatment.

For information on PPI use see Proton Pump Inhibitor (PPIs) monograph.


  Interaction(s) with Common Anaesthetic Agents

 

Local Anaesthetics

Cimetidine slightly reduces clearance of intravenous lidocaine and raises levels in some patients, leading to toxicity in some patients. Monitor for signs of lidocaine toxicity (e.g. bradycardia, hypotension, pins and needles) and reduce dose as necessary. Ranitidine appears not to interact and may be a suitable alternative2.

One study suggests that cimetidine may raise plasma levels of lidocaine (given as an epidural), but other studies have found no effect. There is no clear clinical significance, but bear this interaction in mind in case of lidocaine adverse effects2.

Cimetidine and ranitidine appear to modestly raise the plasma levels of bupivacaine (given as an epidural). No clinical significance has been demonstrated, but bear this interaction in mind in case of bupivacaine adverse effects2.

Opioids (also see Interaction(s) with other Common Medicines used in the Perioperative Period)

Alfentanil (and possibly fentanyl) plasma concentrations are increased by cimetidine – monitor for prolonged and increased sedation and adjust dose accordingly2.

Benzodiazepines

Cimetidine increases the plasma concentration of diazepam and possibly other benzodiazepines. If increased benzodiazepine effects occur (e.g. drowsiness), consider changing to a non-interacting H2-receptor antagonist (e.g. ranitidine)2.

  Interaction(s) with other Common Medicines used in the Perioperative Period


Opioids (also see Interaction(s) with other Common Anaesthetic Agents)

H2RAs may enhance the effects of some opioid analgesics (e.g. morphine, pethidine)2, 3. There have been isolated reports of adverse effects including apnoea, muscle twitching (cimetidine), and confusion (cimetidine and ranitidine)3. The clinical significance of this interaction is uncertain, but is probably limited. However, some manufacturers advise caution2.

The UK manufacturer predicts that cimetidine will inhibit the metabolism of oxycodone (by inhibiting CYP3A4). Due to lack of evidence, the clinical significance of this interaction is unclear. Until more is known be alert for increased oxycodone adverse effects (such as sedation, constipation, respiratory depression) if used concurrently with cimetidine2.


  Further Information


H2RAs vs. Proton Pump Inhibitors (PPIs)

Superiority of either class of acid-suppressing medication given perioperatively to reduce the risk of aspiration has not been definitely proven, although the majority of evidence supports the pre-operative administration of H2RAs in most patients, with PPI therapy being reserved for patients on chronic acid suppression who may have developed some degree of tolerance to such chronic acid suppression4, 5. Also see Proton Pump Inhibitors (PPIs) monograph.


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 22nd June 2019]
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 23rd June 2019]
  3. Opioid Analgesics. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 23rd June 2019]
  4. Aspiration syndromes (Gastrointestinal Drugs – Management of Gastrointestinal Disorders). In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 23rd June 2019]
  5. Medscape. Acid Suppression in the Perioperative Setting: Acid-Related Pulmonary Complications. www.medscape.org [Accessed 22nd June 2019]