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Undesirable effects
The following adverse drug reactions have been identified or suspected in the clinical trials programme
for esomeprazole and post-marketing. None was found to be dose-related. The reactions are classified
according to frequency (common >1/100, <1/10; uncommon >1/1000, <1/100; rare >1/10000, <1/1000;
very rare <1/10000).
Blood and lymphatic system disorders
Rare: Leukopenia, thrombocytopenia
Very rare: Agranulocytosis, pancytopenia
Immune system disorders
Rare: Hypersensitivity reactions e.g. angioedema and anaphylactic reaction/shock
Metabolism and nutrition disorders
Uncommon: Peripheral oedema
Rare: Hyponatraemia
Psychiatric disorders
Uncommon: Insomnia
Rare: Agitation, confusion, depression
Very rare: Aggression, hallucinations
Nervous system disorders
Common: Headache
Uncommon: Dizziness, paraesthesia, somnolence
Rare: Taste disturbance
Eye disorders
Rare: Blurred vision
Ear and labyrinth disorders
Uncommon: Vertigo
Respiratory, thoracic and mediastinal disorders
Rare: Bronchospasm
Gastrointestinal disorders
Common: Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting
Uncommon: Dry mouth
Rare: Stomatitis, gastrointestinal candidiasis
Hepatobiliary disorders
Uncommon: Increased liver enzymes
Rare: Hepatitis with or without jaundice
Very rare: Hepatic failure, encephalopathy in patients with pre-existing liver disease
Skin and subcutaneous tissue disorders
Uncommon: Dermatitis, pruritus, rash, urticaria
Rare: Alopecia, photosensitivity
Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)
Musculoskeletal, connective tissue and bone disorders
Rare: Arthralgia, myalgia
Very rare: Muscular weakness
Renal and urinary disorders
Very rare: Interstitial nephritis
Reproductive system and breast disorders
Very rare: Gynaecomastia
General disorders and administration site conditions
Rare: Malaise, increased sweating
Overdose
There is very limited experience to date with deliberate overdose. The symptoms described in
connection with 280 mg were gastrointestinal symptoms and weakness. Single doses of 80 mg esomeprazole were uneventful. No specific antidote is known. Esomeprazole is extensively plasma
protein bound and is therefore not readily dialyzable. As in any case of overdose, treatment should be
symptomatic and general supportive measures should be utilised.
Pharmacodynamic properties
Esomeprazole, is the S-isomer of omeprazole and reduces gastric acid secretion through a specific
targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. Both the R-
and S-isomer of omeprazole have similar pharmacodynamic activity.
Site and mechanism of action
Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic
environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase – the acid pump and inhibits both basal and stimulated acid secretion.
Effect on gastric acid secretion
After oral dosing with esomeprazole 20 mg and 40 mg the onset of effect occurs within one hour. After
repeated administration with 20 mg esomeprazole once daily for five days, mean peak acid output after
pentagastrin stimulation is decreased 90% when measured 6 - 7 hours after dosing on day five.
After five days of oral dosing with 20 mg and 40 mg of esomeprazole, intragastric pH above 4 was
maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic GERD
patients. The proportion of patients maintaining an intragastric pH above 4 for at least 8, 12 and
16 hours respectively were for esomeprazole 20 mg 76%, 54% and 24%. Corresponding proportions for
esomeprazole 40 mg were 97%, 92% and 56%.
Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid
secretion and exposure has been shown.
Therapeutic effects of acid inhibition
Healing of reflux esophagitis with esomeprazole 40 mg occurs in approximately 78% of patients after
four weeks, and in 93% after eight weeks.
One week treatment with esomeprazole 20 mg b.i.d. and appropriate antibiotics, results in successful
eradication of Helicobacter pylon in approximately 90% of patients. After eradication treatment for one
week there is no need for subsequent monotherapy with antisecretory drugs for effective ulcer healing
and symptom resolution in uncomplicated duodenal ulcers.
Other effects related to acid inhibition
During treatment with antisecretory drugs serum gastrin increases in response to the decreased acid
secretion.
An increased number of ECL cells possibly related to the increased serum gastrin level, have been
observed in some patients during the long term treatment with esomeprazole.
During long-term treatment with antisecretory drugs gastric glandular cysts have been reported to occur
at a somewhat increased frequency. These changes are a physiological consequence of pronounced
inhibition of acid secretion, are benign and appear to be reversible.
In two studies with ranitidine as an active comparator, Nexium showed better effect in healing of gastric
ulcers in patients using NSAIDs, including COX-2 selective NSAIDs.
In two studies with placebo as comparator, Nexium showed better effect in the prevention of gastric
and duodenal ulcers in patients using NSAIDs (aged >60 and/or with previous ulcer), including COX-2
selective NSAIDs.
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