Prilosec (Omeprazole)

Boots Pharmacy Heartburn 10 mg Tablets. Omeprazole

What Is This Medicine For?

This medicine contains omeprazole, which belongs to a group of medicines called proton pump inhibitors. They reduce the amount of acid in your stomach.
It can be used to relieve acid reflux and heartburn, but it will not immediately relieve symptoms.

What Is in This Medicine?

Each gastro-resistant coated tablet contains Omeprazole 10 mg as the active ingredient.
As well as the active ingredient, the tablets also contain lactose monohydrate, sodium starch glycolate, sodium stearate, sodium stearyl fumarate, hypromellose acetate succinate, talc, triethyl citrate, monoethanolamine, sodium lauryl sulfate, sepisperse AP-3527 (containing propylene glycol, titanium dioxide (E171), red iron oxide (E172), hypromellose, yellow iron oxide (E172)), carnauba wax. The pack contains 14 brownish-pink, capsule-shaped film-coated tablets.

Before You Take This Medicine

This medicine can be taken by adults aged 18 years and over. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.

Do not take:

• if you are allergic to any of the ingredients;
• if you are under 18 years old;
• if you have an intolerance to some sugars unless your doctor tells you to (this medicine contains lactose);
• if you are pregnant or breastfeeding.

Talk to your doctor:

• If you have had to continuously take indigestion or heartburn medicine for 4 weeks or more to control your symptoms.
• If you have long-term recurrent symptoms of indigestion or heartburn.
• If you are 45 years old or older, and this is the first time you have had these symptoms, or your symptoms have recently changed.
• If you have lost weight without effort or are frequently tired or run down.
• If you have a bleeding stomach (you may be sick, and it contains blood or dark particles that look like coffee grounds, pass blood in your stools or pass black tarry stools).
• If you have a lump in your stomach.
• If you have stomach pain, pain while swallowing, or difficulty swallowing.
• If you are persistently feeling sick.
• If you have had a stomach ulcer or surgery.
• If you have jaundice or any other liver or kidney problems.
• If you are due to have an endoscopy or a breath test called a C-urea test.
• If you are 45 years old or over and taking any non-prescription (over-the-counter) medicines for indigestion or heartburn regularly.

Other Important Information

Driving and using machines: This medicine may cause drowsiness on rare occasions. You should not drive or operate machinery until you are sure you are not affected.

This medicine reduces the amount of acid your stomach produces and can upset the bacteria in your stomach. This may make you more susceptible to food poisoning.

Tell the doctor you are taking these tablets if you must pass blood tests.

Pregnancy

Proton pump inhibitors are not generally licensed for use during pregnancy (although the UK has licensed omeprazole for such use). Still, a meta-analysis of 5 studies of exposure to proton pump inhibitors during the first trimester, involving 593 exposed infants, found the relative risk of significant abnormalities associated with such exposure to be only 1.18, with a 95% confidence interval ranging from 0.72 to 1.94.

Meta-analysis of exposures to omeprazole (from 4 studies only) gave a relative risk of 1.05 (95% confidence interval 0.59 to 1.85). It was concluded that exposure to proton pump inhibitors, especially omeprazole, did not pose a crucial teratogenic risk. A retrospective epidemiological study of data from the Swedish Medical Birth Registry, which identified 955 exposed infants, also found no evidence of significant risk after exposure to omeprazole during pregnancy.

Precautions

Before giving omeprazole or other proton pump inhibitors to patients with gastric ulcers, the possibility of malignancy should be excluded since these drugs may mask symptoms and delay diagnosis. Omeprazole and other proton pump inhibitors should be used cautiously in hepatic impairment, and dose adjustment may be required.

Gastric Carcinoma

Proton pump inhibitors relieve dyspeptic symptoms associated with gastric carcinoma and can, therefore, delay its diagnosis. In addition, there is some evidence that they may also endoscopically ‘heal’ early gastric carcinoma so that the diagnosis is missed. Consequently, some commentators recommend that proton pump inhibitors should not be prescribed for symptom control before endoscopy in patients at risk for gastric carcinoma.

Helicobacter Infection

Treatment with proton pump inhibitors may cause false-negative results in the urea breath test for Helicobacter pylori infection. In one study in patients with H. pylori infection, 4 weeks of treatment with lansoprazole 30 mg daily caused 33% of patients to have negative urea breath tests. The breath test became positive again in all patients within 2 weeks of stopping lansoprazole therapy. In a similar study, 52% of patients had negative urea breath tests for Helicobacter pylori while receiving omeprazole 20 mg daily, and the breath test became positive again in all patients within 2 to 6 days of stopping treatment. The manufacturers of the urea breath test for Helicobacter pylori recommend that it should not be performed for at least 2 weeks after stopping treatment with an antisecretory drug. For a discussion of the link between proton pump inhibitors, H. pylori, and gastritis, see under Gastrointestinal Tumours above.

Hepatic Impairment

In patients with cirrhosis, an increase in omeprazole bioavailability and elimination half-life has been reported. For dosage adjustment in hepatic impairment, see Administration in Hepatic Impairment below.

Uses and Administration

Omeprazole is a proton pump inhibitor. It suppresses the secretion of gastric acid by inhibiting the enzyme system of hydrogen/potassium adenosine triphosphatase (H+/K+ ATPase), the ‘proton pump’ of the gastric parietal cell. It is used in conditions where inhibition of gastric acid secretion may be beneficial, including aspiration syndromes, dyspepsia (below), gastro-oesophageal reflux disease, peptic ulcer disease, and the Zollinger-Ellison syndrome.

Esomeprazole, an isomer of omeprazole, is also used.

Omeprazole may be given orally as the base or magnesium salt or intravenously as the sodium salt. Doses are expressed in terms of the base. Omeprazole magnesium 10.32 mg and omeprazole sodium 10.64 mg are each equivalent to about 10 mg of omeprazole. To relieve acid-related dyspepsia, omeprazole is given orally in doses of 10 or 20 mg daily for 2 to 4 weeks.

The usual dose for treating gastro-oesophageal reflux disease is 20 mg orally once daily for 4 weeks, followed by a further 4 to 8 weeks if not fully healed. In refractory oesophagitis, a dose of 40 mg daily may be used. Maintenance therapy after healing of oesophagitis is 20 mg once daily, and for acid reflux is 10 mg daily. For dosage in children, see below. In managing peptic ulcer disease, a single daily dose of 20 mg orally, or 40 mg in severe cases, is given. Treatment is continued for 4 weeks for duodenal ulcer and 8 weeks for gastric ulcer. Where appropriate, a dose of 10 to 20 mg once daily may be given for maintenance.

To eradicate Helicobacter pylori in peptic ulceration, omeprazole may be combined with antibacterials in dual or triple therapy. Effective triple therapy regimens include omeprazole 20 mg twice daily or 40 mg once daily combined with the following:

• amoxicillin 500 mg and metronidazole 400 mg, both three times daily;
• clarithromycin 250 mg and metronidazole 400 mg (or tinidazole 500 mg), both twice daily;
• amoxicillin 1 g and clarithromycin 500 mg, both twice daily.

These regimens are given for one week. Dual therapy regimens, such as omeprazole 20 mg twice daily or 40 mg daily with either amoxicillin 750 mg to 1 g twice daily or clarithromycin 500 mg three times daily, are less effective and must be given for two weeks. Omeprazole alone may be continued for a further 4 to 8 weeks.

Doses of 20 mg daily orally are used in treating NSAID-associated ulceration. A dose of 20 mg daily may also be used for prevention in patients with a history of gastroduodenal lesions who require continued NS AID treatment.

The initial recommended dosage for patients with the Zollinger-Ellison syndrome is 60 mg orally once daily, adjusted as required. Most patients are effectively controlled by doses of 20 to 120 mg daily, but doses up to 120 mg three times daily have been used. Daily doses above 80 mg should be divided (usually into 2).

Omeprazole is also used to prevent acid aspiration during general anesthesia, in a dose of 40 mg the evening before surgery and a further 40 mg two to six hours before the procedure. The dose of omeprazole may need to be reduced in patients with hepatic impairment (see below).

Parenteral Dosage

In patients, unsuited to receive oral therapy, omeprazole sodium may be given on a short-term basis by intravenous infusion, in a usual dose equivalent to 40 mg of the base for 20 to 30 minutes in 100 mL of sodium chloride 0.9% or glucose 5%. It may also be given by slow intravenous injection. Higher intravenous doses have been given to patients with Zollinger-Ellison syndrome.

Administration in Children

Licensed UK oral doses of omeprazole for the treatment of gastro-oesophageal reflux disease in children 1 year of age and older are determined by body weight as follows:

• 10 to 20 kg: 10 mg once daily;
• over 20 kg: 20 mg once daily.

These doses may be doubled if necessary. Treatment may be given for 4 to 12 weeks.

For gastro-oesophageal reflux disease, acid-related dyspepsia, treatment of duodenal and benign gastric ulcers including NSAID-associated ulceration, prophylaxis of acid aspiration, and Zollinger-Ellison syndrome, the BNFC recommends an oral dose of 700 micrograms/kg once daily in neonates and children 1 month to 2 years of age. If needed, doses may be increased in neonates after 7 to 14 days to 1.4 mg/kg once daily. Some neonates may require up to 2.8 mg/kg once daily. Children’s doses may be increased up to 3 mg/kg (to a maximum of 20 mg) once daily.

For parenteral dosage in children, the BNFC recommends an intravenous dose of 500 micrograms/kg (to a maximum of 20 mg) once daily in children aged 1 month to 12 years. If needed, this may be increased to 2 mg/kg (to a maximum of 40 mg) once daily.

To eradicate helicobacter pylori in children, the BNFC recommends an oral dose of omeprazole 1 to 2 mg/kg (to a maximum dose of 40 mg) once daily. This is given with antibacterial therapy under specialist supervision.

For administration of the tablets or capsules to children, see the Administration section above.

Administration in Hepatic Impairment

The bioavailability and half-life of omeprazole can increase in patients with hepatic impairment. UK licensed product information recommends a maximum daily oral dose of 20 mg; a daily intravenous dose of 10 to 20 mg is considered sufficient.

Asthma

Gastro-oesophageal reflux has been suggested as a potential exacerbating factor for asthma, and acid suppressive therapy with omeprazole has been reported to reduce asthma symptoms in some but not other studies. A meta-analysis of acid-suppressive therapy concluded it was ineffective in improving asthma symptoms in most patients with gastro-oesophageal reflux, and the link between reflux and asthma symptoms has been disputed.

Dyspepsia

Although earlier UK guidelines on the use of proton pump inhibitors in dyspepsia suggested that they should not be used routinely in non-ulcer dyspepsia, subsequent guidelines on its general management in both the UK and the US consider that a 1 -month empirical trial in patients aged under 55 without symptoms suggestive of more severe disease is a valid first-line treatment.

Inflammatory bowel disease

There are a few reports of responses to omeprazole in patients with inflammatory bowel disease. A combination of omeprazole with mesalazine has also been tried.

Scleroderma

Gastro-oesophageal reflux is one of the gastrointestinal manifestations of systemic sclerosis, and proton pump inhibitors such as omeprazole play a significant role in managing such gastrointestinal disease.

How to Take This Medicine

Omeprazole is given orally as tablets or capsules containing enteric-coated pellets or granules, which should be swallowed whole and not crushed or chewed. In children or patients with swallowing difficulties, UK-licensed product information (Losec AstraZeneca) states that the tablet be dispersed in water and then mixed with fruit juice (with a pH less than 5) or yogurt before swallowing without chewing. Similarly, the contents of the capsules can be mixed with water, fruit juice (with a pH less than 5), or yogurt and swallowed without chewing. A mixture of omeprazole and sodium bicarbonate as a powder for oral suspension is available in some countries.

Check the foil is not broken before use. If it is, do not take that tablet.

AGE	How many to take	How often to take
Adults aged 18 years and over	Two	Once a day, before a meal

If your symptoms improve, reduce the number of tablets to one tablet a day. Increase to two tablets a day if your symptoms return.

• You should always take the lowest amount that controls your symptoms.
• Swallow the tablets whole with a drink of water or fruit juice. Do not crush or chew the tablets.
• Do not give to children or adolescents under 18 years.
• Do not take more than the amount recommended above.
• If symptoms do not improve within 2 weeks, talk to your doctor.
• Talk to your doctor if you require continuous treatment for more than 4 weeks to relieve your symptoms.
• Tell your doctor if your symptoms reappear soon after you stop taking these tablets.

Interactions

Before you take these tablets, make sure that you tell your pharmacist about ANY other medicines you might be using at the same time, particularly the following:

Other medicines to reduce stomach acid production (e.g., cimetidine, famotidine, ranitidine, or lansoprazole):

• Diazepam (for your nerves), phenytoin (for epilepsy), warfarin (a blood thinner);
• Ketoconazole, itraconazole or voriconazole (for fungal infections);
• Digoxin (for heart problems);
• Cilostazol (for leg pain);
• Tacrolimus (to reduce the effect on the immune system).

If you need clarification on interactions with any other medicines, talk to your pharmacist. This includes medicines prescribed by your doctor and medicine you have bought for yourself, including herbal and homeopathic remedies.

Omeprazole and other proton pump inhibitors are metabolized by the CytochromeP450 system, primarily by isoenzyme CYP2C19 and, to a smaller extent, by CYP3A4. Inhibitors or inducers of these isoenzymes may affect exposure to omeprazole and other proton pump inhibitors. In turn, proton pump inhibitors may alter the metabolism of some drugs metabolized by these enzymes. Omeprazole may prolong the elimination of diazepam, phenytoin, and warfarin (but see below).

Omeprazole and other proton pump inhibitors can reduce the absorption of drugs such as dasatinib, ketoconazole, and itraconazole, whose absorption is dependent on an acid gastric pH. With voriconazole, the plasma concentration of both drugs may be increased (for further information, see below). Other proton pump inhibitors may be similarly affected by voriconazole. Omeprazole and other proton pump inhibitors should not be used with atazanavir, as it substantially reduces exposure to atazanavir. For further information on interactions between proton pump inhibitors and HIV-protease inhibitors, see Table 1, under Antivirals.

Omeprazole is metabolized primarily by the cytochrome P450 isoenzyme CYP2C19 (see Metabolism chapter below) and may interact with diazepam (see under Gastrointestinal Drugs). Some metabolism of phenytoin, tolbutamide, and the R-enantiomer of warfarin also occurs by CYP2C19, but the effects have been minor. Although some induction of C YP1A2, which metabolizes caffeine and theophylline, has been reported, this does not appear clinically significant.

While some consider the effect of omeprazole on CYP3A4 activity to be insignificant, others have noted an increasing body of evidence that competitive inhibition of intestinal C YP3A4 by omeprazole may affect the first-pass metabolism of some drugs. A review concluded that, while omeprazole and possibly esomeprazole have considerable potential for drug interactions, lansoprazole, pantoprazole, and rabeprazole are associated with a lower incidence of drug interactions.

For a study in vitro suggesting that omeprazole affected CYP3A4 metabolism of tacrolimus, see under Interactions of Tacrolimus. For more on the effect of proton pump inhibitors on tacrolimus, see Gastrointestinal Drugs for reference to the possibility of enhanced digoxin absorption with omeprazole. For a study suggesting that omeprazole reduces the absorption of cyanocobalamin and vitamin C, see Malabsorption above, and for its effect on calcium absorption. 

Clarithromycin

Studies in healthy subjects have indicated that using omeprazole with clarithromycin results in an approximate 30% increase in peak plasma concentrations of omeprazole and an increase in its mean half-life from 1.2 to 1.6 hours. At the same time, plasma concentrations of clarithromycin were also modestly increased, as were local concentrations in gastric tissue and mucus. Clarithromycin inhibits the metabolism of omeprazole mediated by the cytochrome P450 isoenzyme CYP3A4. The interaction may contribute to the benefits of combined therapy for Helicobacter pylori infection.

Fluvoxamine

Omeprazole and other proton pump inhibitors are metabolized mainly by cytochrome P450 isoenzyme C YP2C19, which shows genetically determined polymorphism, yielding extensive metabolizers and poor metabolizers. Fluvoxamine increased exposure to omeprazole, lansoprazole, and rabeprazole in patients with extensive metabolizers but did not affect pharmacokinetic parameters in poor metabolizers. Dose reductions may need to be considered in patients treated with fluvoxamine and proton pump inhibitors.

Voriconazole

When omeprazole is given with voriconazole, exposure to both drugs is increased. UK-licensed product information for omeprazole states that a dose adjustment of omeprazole is not routinely indicated unless patients have severe hepatic impairment and long-term therapy is indicated. However, UK-licensed product information for voriconazole states that, while no dosage adjustment is considered necessary for voriconazole, when patients already receiving omeprazole are started on voriconazole, the dose of omeprazole should be halved. Other proton pump inhibitors may be similarly affected by voriconazole.

Pharmacokinetics

Omeprazole is rapidly but variably absorbed after oral doses. Absorption is not significantly affected by food. Omeprazole is acid-labile, and the pharmacokinetics of the various formulations developed to improve oral bioavailability may vary. The absorption of omeprazole also appears to be dose-dependent. Increasing the dosage above 40 mg has been reported to increase the plasma concentrations non-linearly because of saturable first-pass hepatic metabolism. In addition, bioavailability is higher after long-term use.

The bioavailability of omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with hepatic impairment, but is not markedly affected in patients with renal impairment. On absorption, omeprazole is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxy-omeprazole and to a small extent by CYP3A4 to form omeprazole sulfone. The metabolites are inactive and are excreted mainly in the urine and, to a lesser extent, in bile. The elimination half-life from plasma is reported to be about 0.5 to 3 hours. Omeprazole is about 95% bound to plasma proteins.

Metabolism

The major enzyme involved in omeprazole metabolism is cytochrome P450 isoenzyme CYP2C19. This enzyme is polymorphically expressed, and individuals deficient in the enzyme are poor metabolizers of omeprazole. This occurs in about 3% of Caucasians and 15% of Chinese, Japanese, and Koreans. These individuals have markedly higher plasma concentrations of omeprazole, and they may require dosage adjustment. Some omeprazole is metabolised by CYP3A4, and some by CYP2D6 to form desmethylomeprazole.

! If you take too many tablets, talk to a doctor immediately. Take your medicine and this leaflet with you.

Overdosage

There is a report of 2 cases of overdosage with omeprazole. The major clinical features were drowsiness, headache (possibly due to a metabolite), and tachycardia. Both patients recovered uneventfully without specific treatments.

Adverse Effects

Proton pump inhibitors are generally well tolerated, with relatively infrequent adverse effects. The adverse effects reported most often with omeprazole and other proton pump inhibitors have been headache, diarrhea, and skin rashes; they have sometimes been severe enough to require stopping treatment. Other effects include pruritus, dizziness, fatigue, constipation, nausea and vomiting, flatulence, abdominal pain, arthralgia and myalgia, urticaria, and dry mouth.

Isolated cases of photosensitivity, bullous eruption, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred. Hypersensitivity reactions have been reported, including fever, bronchospasm, angioedema, and anaphylaxis. Effects on the CNS include occasional insomnia, drowsiness, vertigo, reversible confusional states, agitation, depression, and hallucinations that have occurred in severely ill patients.

Raised liver enzymes and isolated cases of hepatitis, jaundice, hepatic failure, and hepatic encephalopathy have been reported. Other adverse effects reported rarely include paraesthesia, blurred vision, alopecia, stomatitis, increased sweating, taste disturbances, peripheral edema, malaise, hyponatremia, blood disorders (including agranulocytosis, leucopenia, and thrombocytopenia), gynaecomastia, impotence, and interstitial nephritis. Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid-suppressive effects.

Early toxicological studies identified carcinoid-like tumors of the gastric mucosa in rats given very high doses of omeprazole over long periods. This is reviewed in more detail in the Gastrointestinal Tumours section below.

Incidence of Adverse Effects

Prescription-event monitoring for 16 205 patients for whom omeprazole was prescribed, 17 329 with prescribed lansoprazole, and 11 541 with prescribed pantoprazole, indicated that adverse events were reported infrequently. Gastrointestinal disturbance and headache were the most common among them. The most commonly reported cases of diarrhea per 1000 days of exposure were 0.18 for omeprazole, 0.39 for lansoprazole, and 0.23 for pantoprazole. Despite the inherent biases of such a cohort study, there did seem to be some evidence that lansoprazole might be associated with a somewhat more significant risk of diarrhea, particularly in elderly patients.

Effects on the Blood

There have been rare cases of leucopenia, agranulocytosis, thrombocytopenia, and pancytopenia with omeprazole and other proton pump inhibitors such as lansoprazole and pantoprazole. Auto-immune hemolytic anemia has also been reported with omeprazole.

Effects on the Cardiovascular System

Results and preliminary analyses from 2 studies raised concerns about a possible increased risk of myocardial infarction, cardiac failure, and cardiac-related sudden death in patients taking omeprazole or esomeprazole compared with patients who received surgery for gastro-oesophageal reflux disease. However, an FDA safety review found that patients who underwent surgery tended to be younger and less likely to have a history of cardiac problems or risk factors than those treated with one of the drugs.

The FDA concluded that long-term use of these drugs is not likely to be associated with an increased risk of cardiac problems. However, while Health Canada considered that there was no evidence to support such an increased risk with long-term use of esomeprazole, they could not make such a definitive conclusion for omeprazole.

Effects on the Endocrine System

Up to December 1991, WHO had received 30 reports of impotence or gynecomastia, possibly due to omeprazole. 15 of these reports were impotence, 13 of gynecomastia in men, and 2 of breast enlargement in women. The Spanish Pharmacovigilance System reported 24 cases of gynaecomastia associated with using proton pump inhibitors, including lansoprazole and rabeprazole, between January 1982 and July 2006. In most of the cases, gynaecomastia improved after stopping the drug. For reference to a case-control study showing no statistical link between gynaecomastia and omeprazole, see under Cimetidine.

Effects on the Eyes

Visual disturbances associated with the use of omeprazole have included 6 cases of irreversible blindness or visual impairment in severely ill patients given the drug intravenously and 13 cases of visual disturbances associated with oral use. As a result of concern about these effects, the availability of intravenous omeprazole was restricted in Germany. However, omeprazole and these ocular effects have not established a causal link.

Suggestions that visual (and also auditory) impairment could follow drug-induced vasculitis” appear to be contentious.’” A cohort study involving 140 128 patients receiving antisecretory therapy, 33 988 of whom received omeprazole, found no evidence that any of the drugs used was associated with a significant increase in the risk of vascular or inflammatory disorders of the eye; however, the statistical power of this study was not high.

Effects on the Kidneys

Acute interstitial nephritis developed in 2 elderly patients given omeprazole for treating gastro-oesophageal reflux disease. When the drug was stopped, renal function improved rapidly in 1 patient but recurred upon rechallenge. In the other patient, renal function remained severely affected for several months. It was postulated that this adverse effect might have an allergic mechanism. In these cases, interstitial nephritis was associated with rash and eosinophilia; however, a further 2 cases of acute interstitial nephritis associated with omeprazole therapy in elderly patients’ did not exhibit these symptoms. In another report, an associated rash without eosinophiluria was seen.

The Australian Adverse Drug Reactions Advisory Committee (ADRAC) stated in April 2003 that it had received 18 biopsy-confirmed reports of interstitial nephritis associated with the use of omeprazole. These patients had presented with symptoms including weight loss, malaise, fever, and nausea; polyuria and polydipsia occurred in one case. Most patients had raised plasma-urea and/or plasma-creatinine concentrations.

ADRAC had also received 2 reports of interstitial nephritis associated with rabeprazole. A case report (in March 2005) of 2 cases of interstitial nephritis associated with the omeprazole isomer esomeprazole noted that, by October 2004, the manufacturer had reported being aware of some 15 cases worldwide possibly associated with the drug, and at least 200 associated with omeprazole. Acute interstitial nephritis has also been associated with using pantoprazole in an elderly woman to treat gastro-oesophageal reflux disease.

Effects on the Liver

Raised liver enzymes have occurred with omeprazole and other proton pump inhibitors, and there have been isolated cases of hepatotoxicity. For a study suggesting a relatively low incidence of acute liver injury in patients receiving omeprazole, see the Cimetidine section.

Effects on the Musculoskeletal System

Progressive muscular weakness suggestive of myopathy developed in a 78-year-old patient given oral omeprazole. After 4 weeks of treatment, the patient required assistance in walking and rising from squatting. Weakness resolved on withdrawal of the drug but returned on rechallenge. Acute myopathy has also been reported after a single infusion of omeprazole. Analysis of the WHO adverse drug reaction database in March 2005 revealed 868 reports associating proton pump inhibitors with myalgia, of which 292 cases had symptoms indicative of muscle disorders, including polymyositis and rhabdomyolysis Reports implicated omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole, and it was suggested that myopathy was probably a class effect.

The mechanism might involve the induction of auto-immune antibodies. A report of 5 cases of arthralgia, sometimes associated with swelling of the affected joints, in patients receiving omeprazole also noted that some reported cases of omeprazole-associated headache were accompanied by arthralgia or myalgia. In another case, arthralgia in a patient with a hereditary myopathy receiving omeprazole appeared to represent one aspect of a drug-induced lupus syndrome, being accompanied by malaise, fever, Raynaud’s phenomenon, raised antinuclear antibody titers, and anti-cardiolipin and antihistone antibodies. Symptoms resolved on withdrawal of the drug.

A case of eosinophilia and myalgia related to lansoprazole treatment has been reported.

There has also been a report of 2 cases of acute gout associated with omeprazole in one patient. Symptoms, which resolved on withdrawal, recurred on rechallenge. However, case-control studies have failed to show an increased risk of polyarthralgia or gout associated with omeprazole use.

A large case-control study found an increased risk of hip fracture with more than 1 year of proton pump inhibitor therapy, especially with those patients on high doses. The authors theorized that calcium malabsorption secondary to acid suppression may explain this association. While further studies were deemed necessary to confirm these findings, they suggested that calcium intake be emphasized in elderly patients taking proton pump inhibitors.

Effects on the Nervous System

Ataxia has been reported in a patient given omeprazole, and symptoms resolved on stopping the drug. A patient given rabeprazole developed marked anxiety with panic attacks, episodic night terrors, confusion, and attention deficit. Her symptoms resolved 2 days after stopping therapy. She was given esomeprazole a month later with no adverse neuropsychiatric symptoms. The authors hypothesized that rabeprazole use had resulted in significantly greater plasma gastrin concentrations than esomeprazole, which may have affected gastrin receptors in the brain.

Effects on the Respiratory System

An intractable, dry, nonproductive cough started abruptly in a 42-year-old non-smoker given omeprazole for gastro-oesophageal reflux disease (GORD). The cough was initially thought to be related to the GORD, and treatment was continued for 4 months without any cessation. Omeprazole was stopped, and the cough ceased abruptly, with no recurrence during a 2-year follow-up.

Effects on the Skin

An extensive blistering erythematous skin rash in an elderly woman given omeprazole was characteristic of acute disseminated epidermal necrosis. The UK CSM had received 223 reports of cutaneous reactions to omeprazole up to August 1992, including 6 of erythema multiforme, but none of this severity. Other severe reactions that have subsequently been reported include a toxic bullous skin reaction, exfoliative dermatitis, erythema multiforme, toxic erythema, and dermatomyositis.

One patient developed exfoliative dermatitis with both omeprazole and lansoprazole. The authors of this report noted that by January 1998, a total of 1296 skin reactions to omeprazole, 500 to lansoprazole, and 44 to pantoprazole had been reported to the CSM. Most were non-specific rashes, pruritus, urticaria, erythematous rashes, and photosensitive eruptions. A lichenoid reaction in a patient taking omeprazole cleared after ceasing the drug but recurred during treatment with lansoprazole and pantoprazole.

Proton pump inhibitors, including esomeprazole, have been reported to worsen vitiligo. For a report of urticaria and angioedema possibly associated with omeprazole formulation, see the Hypersensitivity section below. For the association of rash with interstitial nephritis, see Effects on the Kidneys above.

Fever

Fever, associated with severe myalgia and headache, was seen in a 64-year-old man on 2 occasions, several hours after taking a dose of esomeprazole. Although it was suggested that the patient’s hyperpyrexia was due to a hypersensitivity reaction, the authors argued that esomeprazole may have interfered with the hypothalamic regulatory centers of body temperature.

Gastrointestinal Tumours

Early toxicological studies in rats given high doses of omeprazole over 2 years identified carcinoid tumors of the gastric mucosa associated with a complete block of gastric acid secretion leading to hypergastrinemia and hyperplasia of enterochromaffin-like cells. This has been the main issue concerning the safety of omeprazole and other proton pump inhibitors and initially led to restrictions in use and duration of treatment. A drug manufacturer, Glaxo, developed a new test to detect the genotoxicity of antisecretory drugs, indicating that omeprazole’s genotoxic effect could not be discounted.

This study was heavily criticized; more established genotoxicity tests have been reported to be negative for omeprazole, and other groups have not been able to replicate the findings with the new test. The lowest doses at which Glaxo found a genotoxic effect of omeprazole were 10 to 20 mg/kg, and the clinical significance of their results was questioned. Long-term studies of omeprazole in patients with Zoilinger-Ellison syndrome have found no increase in fasting serum-gastrin concentrations and no evidence of gastric carcinoid tumors.

For mention of the risk of proton pump inhibitors delaying the diagnosis of gastric carcinoma, see the Precautions section below. Hypergastrinaemia can occur with short- and long-term omeprazole therapy and may be higher in patients with Helicobacter pylori infection. Patients with H. pylori eradicated before long-term omeprazole treatment had lower gastrin concentrations than those without since Helicobacter pylori eradication reduced the pretreatment gastrin concentrations.

Helicobacter pylori is also a cause of atrophic gastritis, another risk factor for stomach cancer, and one study found that omeprazole increased the risk of atrophic gastritis in Helicobacter pylori-positive patients with gastro-oesophageal reflux disease. However, the results of this study require confirmation since it was nonrandomized and retrospective. Nevertheless, some have suggested that it may be appropriate to eradicate Helicobacter pylori before long-term treatment with a proton pump inhibitor. Conversely, there is some evidence that H. pylori may be protective in gastro-oesophageal reflux disease.

There has been a report of gastric polyps developing in 3 of 8 patients after receiving omeprazole 20 or 40 mg daily for one year. A subsequent report noted that these omeprazole-induced fundic gland polyps had remained asymptomatic and non-malignant for up to five years after their onset. Further long-term omeprazole studies may be needed before a realistic risk assessment can be made.

Hypersensitivity

Cases of anaphylactic reactions after treatment with omeprazole, lansoprazole, and pantoprazole have been reported in the literature and by WHO.

Urticaria, facial angioedema, and bronchospasm in a patient given omeprazole capsules did not recur when the patient was given omeprazole granules and the reaction might have been precipitated by the ingredients of the capsule shell. See also Effects on the Kidney section and Effects on the Musculoskeletal System section above.

Infection

Oesophageal candidiasis occurred in 2 elderly patients given omeprazole but was successfully treated with anti-fungal therapy. It was postulated that gastric acid secretion and a degree of physiological reflux of acid into the esophagus might typically play a protective role in preventing candidal infection. A case-control study found that yeast was recovered more often from peritoneal cultures in those patients with community-acquired peritonitis who had previously used proton pump inhibitors, although the trend was non-significant.

The profound reduction in acid secretion produced by omeprazole may also predispose to gastrointestinal infection. There is evidence for an increased risk of community-acquired pneumonia, and campylobacter infection, as well as a report of recurrent salmo-nelly infection. Data from cohort and case-control studies suggest gastric acid suppression by proton pump inhibitors may also be a risk factor for Clostridium difficile-associated diarrhea. For evidence of an increased risk of pneumonia in primary-care patients, proton pump inhibitors were prescribed.

Lupus syndrome

For a report of drug-induced lupus syndrome associated with omeprazole therapy, see Effects on the Musculoskeletal System section above.

Malabsorption

Omeprazole has been reported to result in a substantial reduction in cyanocobalamin (vitamin B12) absorption, probably related to increased gastric pH and indicating a potential risk of vitamin deficiency with long-term therapy. UK licensed product information recommends that severely ill children who may have borderline body stores of cyanocobalamin should have serum vitamin B12 concentrations monitored if they require long-term therapy. Omeprazole has also been reported to impair the bioavailability of dietary vitamin C. Fat malabsorption, secondary to increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum, has also been reported with omeprazole treatment. For the suggestion that proton pump inhibitors can cause calcium malabsorption, see the Effects on the Musculoskeletal System section above.

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

Synonyms: H-168/68; Omepratsoli; Omeprazol; Omeprazolas; Omeprazolum

BAN: Omeprazole

USAN: Omeprazole

INN: Omeprazole [rINN (en)]

INN: Omeprazol [rINN (es)]

INN: Oméprazole [rINN (fr)]

INN: Omeprazolum [rINN (la)]

INN: Омепразол [rINN (ru)]

Chemical name: (RS)-5-Methoxy-2-(4-methoxy-3,5-dimethyl-2-pyridylmethylsulphinyl)benzimidazole

Molecular formula: C17H19N3O3S =345.4

CAS: 73590-58-6

ATC code: A02BC01

Read code: y01QN

Pharmacopoeias. In China, Europe, and the US.

European Pharmacopoeia, 6th ed. (Omeprazole). A white or almost white powder. It exhibits polymorphism. Very slightly soluble in water, sparingly soluble in alcohol, and in methyl alcohol, soluble in dichloromethane. It dissolves in dilute solutions of alkali hydroxides. Store in airtight containers at a temperature between 2° and 8°. Protect from light.

The United States Pharmacopeia 31, 2008 (Omeprazole). A white to off-white powder. Very slightly soluble in water, sparingly soluble in alcohol and in methyl alcohol, soluble in dichloromethane. Store in airtight containers at a temperature not exceeding 8°. Protect from moisture.

Omeprazole Magnesium Drug Approvals

(BANM, US Adopted Name, rINNM)

BAN: Omeprazole Magnesium [BANM]

USAN: Omeprazole Magnesium

INN: Omeprazole Magnesium [rINNM (en)]

INN: Omeprazol magnésico [rINNM (es)]

INN: Oméprazole Magnesique [rINNM (fr)]

INN: Magnesii Omeprazolum [rINNM (la)]

INN: Магния Омепразол [rINNM (ru)]

Molecular formula: C34H36MgN6O6S2 =713.1

CAS: 95382-33-5

ATC code: A02BC01

Pharmacopoeias. In US.

The United States Pharmacopeia 31, 2008 (Omeprazole Magnesium). A white to off-white powder. Very soluble in water and in dichloromethane, slightly soluble in alcohol, sparingly soluble in methyl alcohol. Store in airtight containers. Protect from light.

Omeprazole Sodium Drug Approvals

(BANM, US Adopted Name, rINNM)

Synonyms: Omepratsolinatrium; Omeprazol sódico; Omeprazol sodná sůl monohydrát; Omeprazol-nátrium; Omeprazolnatrium; Omeprazolo natrio druska; Omeprazolum Natricum; Omeprazolum Natricum Monohydricum

BAN: Omeprazole Sodium [BANM]

USAN: Omeprazole Sodium

INN: Omeprazole Sodium [rINNM (en)]

INN: Omeprazol sódico [rINNM (es)]

INN: Oméprazole Sodique [rINNM (fr)]

INN: Natrii Omeprazolum [rINNM (la)]

INN: Натрий Омепразол [rINNM (ru)]

Molecular formula: C17H18N3NaO3S =367.4

CAS: 95510-70-6

ATC code: A02BC01

Pharmacopoeias. In Europe.

European Pharmacopoeia, 6th ed. (Omeprazole Sodium). A white or almost white hygroscopic powder. It is freely soluble in water and in alcohol, very slightly soluble in dichloromethane, and soluble in propylene glycol. The pH of a 2% solution in water is 10.3 to 11.3. Store in airtight containers. Protect from light.

How to store this medicine

Do not store above 30°C. Store in the original package.

Keep this medicine safe out of the sight and reach of children, preferably in a locked cupboard.

Use before the expiry date.

FAQ

Question: I have systemic Mastocytosis. My Dr. has put me on PRILOSEC. He said it is a Proton Pump Inhibitor. What is a Proton Pump Inhibitor, and how does it work for Mastocytosis?

Answer: Mastocytosis is a disease in which the bone marrow produces excessive numbers of cells known as Mast cells. These cells make many chemicals (mediators) that have an effect on other organs of the body. One such mediator is Histamine; excess of this leads to some of the symptoms of Mastocytosis, including various GI disturbances.

Histamine is a powerful stimulant of Acid secretion by the stomach. The large amount of Histamine in patients with Mastocytosis causes a rise in acid secretion. The end result is ulcer disease and sometimes diarrhea and impaired intestinal absorption. The diarrhea and decreased intestinal absorption happen because of more fluid being produced than the GI tract can handle, and the effect of acid on intestinal enzymes which are needed for digestion.

This does not happen in all those with this rare disease-but it certainly can be a problem when it does. TAGAMET belongs to a class of medications known as H-2 Antagonist; they block some of the effects of Histamine, including acid secretion. Proton Pump Inhibitors (PPIs), such as PRILOSEC, block acid secretion at a different biochemical step in acid production. PPIs do a better job in blocking acid secretion than the H-2′s, and their effects last longer, allowing for less frequent doses.

Question: I have Esophageal reflux condition for years. I am 36 years old and have the pain part of the problem taken care of with the use of Prilosec, which I take daily, however, I still have the reflux…..( the problem is that my gastroenterologist recommends surgery, but my family doctor prefers continued medication). What is your opinion?

Answer: You are not alone in feeling confused as to the best long-term treatment (surgery vs.long-term medication) for esophageal reflux in a young patient. Our gastroenterologist writers are also divided on this issue. As you know, medication treatment of esophageal reflux oftentimes have to be continued indefinitely, because symptoms usually return promptly after stopping medications. Some gastroenterologists and surgeons feel that young individual (36 is young) who is a good surgical risk would benefit from the surgery. There are several reasons for that. With successful surgery by a competent surgeon, many of the present prohibitions in diet, not eating 3 hours before bedtime, etc. would no longer be needed and patient could resume a normal life-style.

The cost of PRILOSEC over a patient’s projected life span far exceeds the cost of surgery. Our experience of long term safety with PRILOSEC is good, but is limited to about 7 years. No one at present can predict the safety of the drug for 30-40 years. One theoretical concern over long term use of PRILOSEC is the potential development of carcinoid tumor (even though no cases have been reported among humans so far). A recent study of patients on PRILOSEC for several years and also infected with Helicobacter Pylori bacteria (a very common stomach infection), has shown a significant increase in the incidence of atrophic gastritis (one of the potential precursors of stomach cancer). In short, using PRILOSEC for several years is most likely safe. But the safety of decades of PRILOSEC use is unknown, and the answer will not be in for another 15 or so years. Some doctors, however, still favor long term medication over surgery. They weigh the theoretical risks of long term medications against the risks of general anesthesia, complications of surgery, or poor results from surgery.

What is a young man like Tony to do? You should ask your gastroenterologist and your family doctor to confer and agree upon a course of action for you. Make sure you have optimized non-medication measures such as reducing excess weight, stopping smoking, alcohol and caffeine, raising head of bed etc. Availability of a competent surgeon experienced in anti-reflux surgery in your community is a very important factor in helping you and your doctor in making this decision.

Preparations

British Pharmacopoeia 2008: Gastro-resistant Omeprazole Capsules; Gastro-resistant Omeprazole Tablets

The United States Pharmacopeia 31, 2008: Omeprazole Delayed-Release Capsules.

Proprietary Preparations

Argentina: Acimed Aziatop Brux Danlox Fabrazol Fendiprazol Gastec Gastroprazol Gastrotem Klomeprax Losec Mucoxol Omeprasec Pepticus-H Pravil Procelac Prysma Regulacid Timezol Ulcozol Zoltenk

Australia: Acimax Losec Maxor Meprazol Omepral Probitor

Austria: Helicostad Losec Lostad Medoprazol Omec Omegastron Omepralan Probitor Semiglerr|-

Belgium: Docomepra Logastric Losec Omepratop Sedacicl

Brazil: Belprazol Bioprazolf Elprazol Estomepe Eupept Fegran Gasec Gaspiren Gastrib Gastrium Gastrozol Klispel Lomepral Loprazol Losaprol Losar Losec Lozap Lozeprel Lozix Meprazan Mesopran Neoprazol Novoprazol Omegastrol Omenax Omep Omepramed Omeprazin Omeprotec Oprazon Peprazol Pepsicaps Prazolex Prazonil Prazotom Ulcecaps Ulcefor Ulcozol Uniprazol Victrix Zolpramex

Canada: Losec

Chile: Lomex Losec Micromex Omeprax Pepticum Prazolo Ulc-Out Ulcelac Ulcrux Zatrol Zomepral

Czech Republic: Apo-Ome Gasec Helicid Lomac Losec Loseprazol Omepirex Omeprol Omolin Onprelen Oprazole Ortanol Pepticum Problok Tulzol Ultop

Denmark: Losec

Finland: Losec

France: Mopral Zoltum

Germany: Antra Gastracid Ome TAD Omenerton Ome-Puren Ome-Q Omebeta Omedoc Omegamma OmeLich Omelind Omep

Greece: Assoprol Belifax Elibactin Elkostop Elkotheran Eselan Esopraz Ezipol Gertalgin Glaveral Inhiplex Kerlofin Lanex Lenar Lomezec Loproc Lordin Losec Lozaprin Malortil Meprolen Novek Odamesol Odasol Ofnimarex Omeprol Penrazol Pipacid Prazolin Probitor Rythmogastryl Sedacid Sieral Silato Ufonitren Veralox Zolldenol

Hong Kong: Losec

Hungary: Losec Omegen Omep Omeprawin Ulzol

India: Biocid Lomac Nogacid Ocid Olit Omezol Promisee UIzol

Indonesia: Contral Dudencer Loklor Losec Meisec Nor-sec Omevell OMZ Onic Opm Oprezol Ozid Prohibit Promezol Pro-top Pumpitor Redusec Regasec Rocer Socid Stomacer Ulzol Zepral Zollocid

Ireland: BySec Lopraz Losamel Losec Losepine Ulcid

Israel: Losec Omepradex

Italy: Antra Losec Mepral Omeprazen

Japan: Omepral

Malaysia: Gasec Losec Medoprazole Omelon Omesec Omez Omezole Probitor Romesec Zenpro Zimor

Mexico: Alboz Aleprozil Apopraza Argarynf Azoran Danovag Domer Gerdex Grizol Hopram Ibax Inhibitron Logazil Lopram Losec Medral Mopral Mornin Olexin Omecaps Ometec Opramid Osiren Ozoken Panzer Pastrizol Pentren Prazidec Prazolit Sarox Solcer Suifac Tarzol Ucetal Ulsen Ultizol Ultromep Usaltron Vulcasid Zoral Zulmedx

The Netherlands: Losec Omeprazostad Omepstad Omezol Omolin Romisan

Norway: Losec

New Zealand: Losec Omezol

Philippines: Gastriloc Hovizol Losec Mepracid Omenole Omepron Omizac OMZ Opehex Peptisolv Premio Promesec Puroxel Risek Tansinel Ulsek Zyom

Poland: Bioprazol Gasec Helicid Losec Notis Omar Ortanol Polprazol Prazol Ulzol

Portugal: Belmazol Bioprazol Eugastrim Gasec Losec Mepraz Novek Nuclosina Omepra Omeratio Omerol Ometon Omezolan Prazentol Prazex Prazolene Proclor Proton

South Africa: Altosec Losec Omez Omiloc Ulzec

Singapore: Losec Ocid Olit Omesec Omezole Penrazole Proceptin Romesec Zenpro Zimor

Spain: Audazol Aulcer Belmazol Ceprandal Dolintol Elgam Emeproton Gastrimut Indurgan Ipirasa Losec Miol Mopral Norpramin Novek Nuclosina Omapren Ompranyt Parizac Pepticum Prysma Sanamidol Ulceral Ulcesep Ulcometion Zimor

Sweden: Losec

Switzerland: Amanol Antra Antramups Gastroprazol Omed omeprabasan Omezol Oprazol

Thailand: Airomet Desec Dosate Duogas Eselan Eucid Gaster Gomec Lomac Losec Madiprazole Meiceral Metsec Miracid Nocid O-Sid Olit Omez Omicap Oprazole Probitor Severon Stomec Ulprazole Zefxon Zimor

Turkey: Demeprazol Erbolin Losec Omegast Omeprazid Omeprol Prosek

UAE: Risek

UK: Heartburn Relief Losec Zanprol

USA: Prilosec

Venezuela: Fordex Gastronol Losec Meprox Omebloc Omevax Omez Omezul Parsolen Prazol Probitor Promezol Tecol

Multi-ingredient

Australia: Klacid HP 7 Losec Hp 7

Brazil: Erradic Helicocid Triplicef Omepramix

Canada: Losec 1-2-3 A Losec 1-2-3 M

Finland: Losec Helira

India: Helipac Nogacid D Okacid D OTC HP Kit

Malaysia: Fylobact Combi

New Zealand: Klacid HP 7 Losec Hp 7

Philippines: OAC Hp7

Russia: Fylobact

South Africa: Losec 20 Triple

USA: Zegerid