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Therapeutics Letter, issue 1, October 1994

Treatment of Non-Ulcer Dyspepsia in Adults: Common Questions about H2-blockers

Complaints referable to the upper gastrointestinal tract are a common presentation to the primary care physician. We are fortunate to have a wide variety of drugs available to manage these conditions including antacids, H2-blockers, sucralfate, misoprostol, and omeprazole. In this letter we will focus on the most widely prescribed drugs, the H2-blockers. The next two letters will concentrate on Helicobacter pylori and gastroesophageal reflux disease.

 There are four H2-blockers available for prescription in British Columbia (see Table). These four drugs all act to reduce gastric acid secretion and are similar chemically and pharmacokineticaly; they are all eliminated mostly by the kidney and they have similar half-lives of around 2 hours.(1) Despite the short half-life, they are all effective in most patients when given once daily at bed-time.(1) Administration of any of the four H2-blockers results in healing after 8 weeks of therapy in 80% of the cases. The approximate clinically equivalent doses are shown in the Table reflecting some difference in potency, which is not of any clinical significance. The safety profile of all four drugs is excellent with a low percentage of patients developing side effects, requiring discontinuing the drug.(1)

    Dose*
Drug
Trade Names
Treatment of 6-8 weeks
mg qhs
Maintenance
mg qhs
Cimetidine Tagamet, Peptol, Nu-Cimet, Apo-Cimetidine, Novo-Cimetidine 800 400
Ranitidine Zantac, Nu-Ranit, Novo-Randine, Apo-Ranitidine 300 150
Famotidine Pepcid, Apo-famotidine, Novo-famotidine 40 20
Nizatidine Axid 300 150

* Reduce by at least one half in patients with renal insufficiency, e.g. many elderly patients.

Commonly asked questions

What about confusion in the elderly?

The outpatient incidence of CNS reactions including confusion is 0.2% or less. There is no evidence of a higher incidence with one H2-blocker as compared with another.(2)

What about drug interactions?

Cimetidine and to a lesser extent ranitidine have the capacity to inhibit the metabolism of some other drugs to a small usually clinically insignificant degree (10 to 30%). Cimetidine only needs to be avoided in combination with the following three drugs: warfarin, phenytoin, and theophylline.

What about gynecomastia?

Cimetidine is associated with a 0.3% overall incidence of gynecomastia; the risk is less with doses less than 1000 mg daily.(3)

Is it possible to switch from one H2-blocker to another?

Patients can be readily switched from one H2-blocker to another in equivalent dose without any risk to the patient.

 How much should the dose be reduced in the elderly?

In the elderly and other patients with reduced renal function the doses used should be 1/2 to 1/4 of the usual doses.(1)

Is it safe to stop H2-blockers in patients who have been on long term maintenance therapy?

Studies have shown that many patients are inappropriately maintained on H2-blockers.(4) Maintenance therapy should be limited to patients with proven recurrent peptic ulcer disease, or severe recurrent dyspepsia. The need for maintenance therapy will be markedly diminished with the appropriate eradication of Helicobacter pylori (see Therapeutics Letter 2). It is safe to abruptly stop the drug in such patients. If a patient develops symptoms consistent with rebound hyperacidity the dose of the drug can be tapered over a 2-3 week period and stopped.

Is there a significant difference in the cost of H2-blockers?

The relative cost of the average maintenance dose of H2-blockers in comparison to the other drugs used in the management of peptic ulcer disease is shown in the Figure.

 Conclusion:

There is little difference between the various H2-blockers other than cost.


References

  1. Feldman M., Burton ME. Histamine2 - receptor antagonists. Standard therapy for acid-peptic diseases. NEJM. 323:1672- 80, 1749-55; 1990.

  2. Cantu TG, Korek JS. Central nervous system reactions to histamine-2 receptor blockers. Ann Int Med. 114:1027-34; 1994.

  3. Rodriguez LAG, Jick H. Risk of gynecomastia associated with cimetidine, omeprazole, and other antiulcer drugs. BMJ. 308: 503-6; 1994.

  4. Carmichael JM, Zell SC. Survey of ulcer recurrence risk factors associated with long-term cimetidine prescribing. Drug Intelligence and Clinical Pharmacy. 21: 452-8; 1987.


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