Zantac and ulcers

Q:Could you please tell me the side effects of Zantac? M D, London......

A:Zantac, or ranitidine, is one of a family of drugs called histamine 2 receptor antagonists, which supposedly have revolutionized the treatment of stomach ulcers. They work by blocking the H2 nerve receptors in the stomach which histamine ordinarily stimulates to produce gastric acid. By inhibiting this action, the H2 blockers reduce both the amount and pepsin content of the acid. They also block the effects of the hormone called gastrin, produced in the stomach to stimulate the production of stomach juices. It is relatively long acting, suppressing gastric acid secretion for 12 hours, so patients are usually given 150 mg to take twice a day or a single bedtime dose of 300 mg. In most cases, claim the manufacturers (Glaxo Laboratories), "healing occurs in four weeks" or in those who don't initially respond, four weeks after that.

The drug is used for Zollinger-Ellison syndrome (where patients suffer from too much stomach acid) and oesophageal reflux disease, and even for those who have chronic episodic heartburn with pain. Lately H2 blockers, as they're called, are also being used to prevent the formation of duodenal ulcers from non steroidal anti inflammatory drugs used to treat arthritis. (There is less convincing evidence for this. In one study, under a third of NSAID patients healed after four weeks; about half after eight weeks NE J Med 1989:320:69-75).

Doctors treating ulcer patients and seeing fast results with the H2 blockers (59 per cent of Zantac patients heal after four weeks; 85 per cent after eight weeks, according to one study) have become so zealous in their use that they have now begun using them as a just in case measure, to prevent relapses. As with Losec (see Drug of the Month, p 7), the long term safety of these drugs hasn't been established with certainty since the oldest one has only been on the market for a little more than a decade. Furthermore, they are far more effective for duodenal than stomach ulcers, which can occur even in individuals with very little stomach acid.

The problem, of course, is that gastric and duodenal ulcers, are chronic, recurring diseases. Many doctors believe that relapses can be prevented by using H2 blockers for maintenance therapy that is, keeping patients on them long term. The problem is that none of the current drugs on the market has been approved for maintenance therapy in the US (in the UK, the entry in the Data Sheet Compendium for Zantac emphasizes that the drug should mainly be used no longer than 12 weeks, although it does mention maintenance treatment at reduced dosages.)

As you'd suspect, there are problems with turning off your stomach acid. Dr Mark Feldman and pharmacist Michael Burton have written (NE J Med, 20 Dec 1993), "Although H2 blockers are effective in accelerating the healing of gastric ulcers, the evidence that they accelerate the relief of symptoms and prevent complications is less convincing."

One of the goals of ulcer therapy is to heal the ulcer completely, particularly since 2 to 5 per cent of apparently benign gastric ulcers are in fact malignant. As Glaxo warns in the Data Sheet Compendium: "Treatment with an H2 antagonist may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition. Accordingly, where gastric ulcer has been diagnosed or in patients of middle age and over with new or recently changed dyspeptic symptoms the possibility of malignancy should be excluded before therapy with Zantac . . . is instituted."

As for side effects, the Physician's Desk Reference offers the usual laundry list: headaches (often severe), insomnia, vertigo, depression, hallucinations, blurred vision, irregular heartbeats, pancreatitis (inflammation of the pancreas), diarrhoea, nausea/vomiting, abdominal discomfort, hepatitis and other liver disorders. "In such circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in exceedingly rare circumstances death has occurred," notes Glaxo in the PDR (it says nothing to this effect in Britain's Data Sheet). They continue: blood count changes, usually reversible, or those rare cases of agranulocytosis (severe blood disorder) have been reported; occasional cases of impotence; hair loss; anaphylactic shock.

It's well to keep in mind that all such ulcer drugs don't deal with the cause of the problem, which easily could recur once the drug is stopped. One area to investigate is a food allergy which in many instances contributes to the development of ulcers. Other contributory factors include smoking and alcohol, prescription drugs and stress, lowered levels of B6 and an infection.