ustment of esomeprazole is not regularly required in either of these situations. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.
Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.
4.6 Pregnancy and lactation
For Nexium, clinical data on exposed pregnancies are insufficient. With the racemic mixture omeprazole data on a larger number of exposed pregnancies stemmed from epidemiological studies indicate no malformative nor foetotoxic effects. Animal studies with esomeprazole do not indicate direct or indirect harmful effects with respect to embryonal/foetal development. Animal studies with the racemic mixture do not indicate direct or indirect harmful effects with respect to pregnancy, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.
It is not known whether esomeprazole is excreted in human breast milk. No studies in lactating women have been performed. Therefore, NEXIUM should not be used during breast-feeding.
4.7 Effects on ability to drive and use machines
No effects have been observed.
4.8 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 very common > 1/10; common >1/100 to <1/10; uncommon >1/1,000 to <1/100; rare >1/10,000 to <1/1,000; very rare <1/10,000; not known (cannot be estimated from the available data).
Blood and lymphatic system disorders
Rare: Leukopenia, thrombocytopenia
Very rare: Agranulocytosis, pancytopenia
Immune system disorders
Rare: Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock
Metabolism and nutrition disorders
Uncommon: Peripheral oedema
Rare: Hyponatraemia
Very rare: Hypomagnesaemia
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
