There is limited information available on the effects of overdoses of Ultop in humans. In literature, doses of up to 560 mg have been described, and occasional reports have been received when single oral doses have been reached of up to 2,400 mg Ultop (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been reported. Also apathy, depression and confusion have been described in single cases.
The symptoms described in connection with Ultop overdose have been transient, and no serious outcome has been reported. The rate of elimination was unchanged (first order kinetics) with increased doses. Treatment, if needed, is symptomatic.
There is limited information available on the effects of overdoses of omeprazole in humans. In the literature, doses of up to 560 mg have been described, and occasional reports have been received when single oral doses have reached up to 2,400 mg omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been reported. Also apathy, depression and confusion have been described in single cases.
The symptoms described have been transient, and no serious outcome has been reported. The rate of elimination was unchanged (first order kinetics) with increased doses. Treatment, if needed, is symptomatic.
Not applicable.
Not applicable.
The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/vomiting.
The following adverse drug reactions have been identified or suspected in the clinical trials programme for Ultop and post-marketing. None was found to be dose-related.
Adverse reactions listed below are classified according to the frequency and System Organ Class (SOC). Frequency categories are defined according to the following convention:
- 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)
| SOC/ Frequency | Adverse reaction |
| Blood and lymphatic system disorders | |
| Rare: | Leukopenia, thrombocytopenia |
| Very rare: | Pancytopenia, agranulocytosis |
| Immune system disorders | |
| Rare: | Hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/ shock |
| Metabolism and nutrition disorders | |
| Rare: | Hyponataemia |
| Not Known: | Hypomagneseamia; severe hypomagnesaemia may result in hypocalcaemia Hypomagnesaemia may also be associated with hypokalaemia. |
| Psychiatric disorders | |
| Uncommon: | Insomnia |
| Rare: | Agitation, confusion, depression |
| Very Rare: | Aggression, hallucinations. |
| Nervous system disorders | |
| Common: | Headache |
| Uncommon: | Dizziness, paresthesia, 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 and vomiting fundic gland polyps (benign) |
| Rare: | Dry mouth, stomatitis, gastrointestinal candidiasis |
| Not known: | Microscopic colitis |
| 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-Johnsonsyndrome, toxic epidermal necrolysis (TEN) |
| Not known | Subacute cutaneous lupus erythematosus |
| Musculoskeletal and connective tissue disorders | |
| Uncommon: | Fracture of the hip, wrist or spine |
| Rare: | Arthralgia, myalgia |
| Very Rare: | Muscular weakness |
| Renal and urinary disorders: | |
| Rare: | Interstitial nephritis |
| Reproductive System and breast disorders: | |
| Very Rare: | Gynaecomastia |
| General disorders and administration site conditions | |
| Uncommon: | Malaise, peripheral oedema |
| Rare: | Increased sweating. |
Paediatric Population
The safety of Ultop has been assessed in a total of 310 children aged 0 to 16 years with acid-related disease. There are limited long term safety data from 46 children who received maintenance therapy of Ultop during a clinical study for severe erosive oesophagitis for up to 749 days. The adverse event profile was generally the same as for adults in short- as well as in long-term treatment. There are no long term data regarding the effects of Ultop treatment on puberty and growth.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Summary of the safety profile
The most common side effects (1-10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence and nausea/vomiting.
Tabulated list of adverse reactions
The following adverse drug reactions have been identified or suspected in the clinical trials programme for omeprazole and post-marketing. None was found to be dose-related. Adverse reactions listed below are classified according to frequency and System Organ Class (SOC). Frequency categories are defined according to the following convention: 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).
| SOC/frequency | Adverse reaction | |
| 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 | ||
| Rare: | Hyponatraemia | |
| Not known: | Hypomagnesaemia; severe hypomagnesaemia may result in hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia. | |
| 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, fundic gland polyps (benign) | |
| Rare: | Dry mouth, stomatitis, gastrointestinal candidiasis | |
| Not known: | Microscopic colitis | |
| 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) | |
| Not known: | Subacute cutaneous lupus erythematosus | |
| Musculoskeletal and connective tissue disorders | ||
| Uncommon: | Fracture of the hip, wrist or spine | |
| Rare: | Arthralgia, myalgia | |
| Very rare: | Muscular weakness | |
| Renal and urinary disorders | ||
| Rare: | Interstitial nephritis | |
| Reproductive system and breast disorders | ||
| Very rare: | Gynaecomastia | |
| General disorders and administration site conditions | ||
| Uncommon: | Malaise, peripheral oedema | |
| Rare: | Increased sweating | |
Paediatric population
The safety of omeprazole has been assessed in a total of 310 children aged 0 to 16 years with acid-related disease. There are limited long-term safety data from 46 children who received maintenance therapy of omeprazole during a clinical study for severe erosive oesophagitis for up to 749 days. The adverse event profile was generally the same as for adults in short- as well as in long-term treatment. There are no long-term data regarding the effects of omeprazole treatment on puberty and growth.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard.
Gastric ECL-cell hyperplasia and carcinoids have been observed in life-long studies in rats treated with Ultop. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition. Similar findings have been made after treatment with H2-receptor antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not from a direct effect of any individual active substance.
Gastric ECL-cell hyperplasia and carcinoids, have been observed in life-long studies in rats treated with omeprazole. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition. Similar findings have been made after treatment with H2-receptor antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not from a direct effect of any individual active substance.
Pharmacotherapeutic group: Proton pump inhibitors, ATC-code: A02BC01
Mechanism of Action:
Ultop, a racemic mixture of two enantiomers, reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once daily dosing.
Ultop is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+, K+-ATPase - the acid pump. This effect on the final step of gastric acid formation process is dose-dependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus.
Pharmacodynamic effects:
All pharmacodynamic effects observed can be explained by the effect of Ultop on acid secretion.
Clinical Efficacy and Safety:
Effect on gastric acid secretion:
Oral dosing with Ultop once daily provides for rapid and effective inhibition of daytime and night-time gastric acid secretion with maximum effect being achieved within 4 days of treatment. With Ultop 20mg, a mean decrease of at least 80% in 24-hour intragastric acidity is then maintained on duodenal ulcer patients, with the mean decrease in peak acid output after pentagastrin stimulation being about 70% 24 hours after dosing.
Oral dosing with Ultop 20mg maintains an intragastric pH of > 3 for a mean time of 17 hours of the 24-hour period in duodenal ulcer patients.
As a consequence of reduced acid secretion and intragastric acidity, Ultop dose-dependently reduces/normalizes acid exposure of the esophagus in patients with gastro-esophageal reflux disease. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) of Ultop and not the actual plasma concentration at a given time.
No tachyphylaxis has been observed during treatment with Ultop.
Effect on H. pylori
H. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer disease. H. pylori is a major factor in the development of gastritis. H. pylori together with gastric acid are major factors in the development of peptic ulcer disease. H. pylori is a major factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric cancer.
Eradication of H. pylori with Ultop and antimicrobials is associated with high rates of healing and long-term remission of peptic ulcers.
Dual therapies have been tested and have been found to be less effective than triple therapies. They could however be considered in cases where known hypersensitivity precludes the use of any triple combination.
Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric count of bacteria normally present in the gastrointestinal tract. Treatment with acid reducing drugs may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and, in hospitalized patients, possibly also Clostridium difficile..
During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
An increased number of ECL cells possibly related to the increased serum gastrin levels, have been observed in some patients (both children and adults) during long term treatment with Ultop. The findings are considered to be of no clinical significance.
Paediatric population
In a non-controlled study in children (1 to 16 years of age) with severe reflux esophagitis, Ultop at doses of 0.7 to 1.4 mg/kg improved esophagitis level in 90 % of the cases and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed gastro-esophageal reflux disease were treated with 0.5, 1.0 or 1.5 mg Ultop/kg. The frequency of vomiting/regurgitation episodes decreased by 50 % after 8 weeks of treatment irrespective of the dose.
Eradication of Helicobacter pylori in children
A randomised, double-blind clinical study (Heliot study) concluded that Ultop in combination with two antibiotics (amoxicillin and clarithromycin) was safe and effective in the treatment of H. pylori infection in children of 4 years old and above with a gastritis: H. pylori eradication rate: 74 % (23/31 patients) with Ultop + amoxicillin + clarithromycin versus 9.4 % (3/32 patients) with amoxicillin + clarithromycin. However, there was no evidence of clinical benefit demonstrated regarding dyspeptic symptoms. This study does not support any information for children aged less than 4 years old.
Pharmacotherapeutic group: Drugs for acid-related disorders, proton pump inhibitors, ATC code: A02BC01
Mechanism of action
Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion through a highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. It is rapidly acting and provides control through reversible inhibition of gastric acid secretion with once daily dosing.
Omeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+ K+-ATPase - the acid pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for highly effective inhibition of both basal acid secretion and stimulated acid secretion, irrespective of stimulus.
Pharmacodynamic effects
All pharmacodynamic effects observed can be explained by the effect of omeprazole on acid secretion.
Effect on gastric acid secretion
Oral dosing with omeprazole once daily provides for rapid and effective inhibition of daytime and night-time gastric acid secretion with maximum effect being achieved within 4 days of treatment. With omeprazole 20 mg, a mean decrease of at least 80% in 24-hour intragastric acidity is then maintained in duodenal ulcer patients, with the mean decrease in peak acid output after pentagastrin stimulation being about 70% 24 hours after dosing.
Oral dosing with omeprazole 20 mg maintains an intragastric pH of > 3 for a mean time of 17 hours of the 24-hour period in duodenal ulcer patients.
As a consequence of reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces/normalizes acid exposure of the oesophagus in patients with gastro-oesophageal reflux disease.
The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) of omeprazole and not to the actual plasma concentration at a given time.
No tachyphylaxis has been observed during treatment with omeprazole.
Effect on H. pylori
H. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer disease. H. pylori is a major factor in the development of gastritis. H. pylori together with gastric acid are major factors in the development of peptic ulcer disease. H. pylori is a major factor in the development of atrophic gastritis which is associated with an increased risk of developing gastric cancer.
Eradication of H. pylori with omeprazole and antimicrobials is associated with, high rates of healing and long-term remission of peptic ulcers.
Dual therapies have been tested and found to be less effective than triple therapies. They could, however, be considered in cases where known hypersensitivity precludes use of any triple combination.
Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in a somewhat increased frequency. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing drugs may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and, in hospitalised patients, possibly also Clostridium difficile.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours. Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
An increased number of ECL cells possibly related to the increased serum gastrin levels, have been observed in some patients (both children and adults) during long term treatment with omeprazole. The findings are considered to be of no clinical significance.
Paediatric population
In a non-controlled study in children (1 to 16 years of age) with severe reflux oesophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved oesophagitis level in 90% of the cases and significantly reduced reflux symptoms. In a single-blind study, children aged 0-24 months with clinically diagnosed gastro-oesophageal reflux disease were treated with 0.5, 1.0 or 1.5 mg omeprazole/kg. The frequency of vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment irrespective of the dose.
Eradication of H. pylori in children
A randomised, double blind clinical study (Héliot study) concluded that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin), was safe and effective in the treatment of H. pylori infection in children age 4 years old and above with gastritis: H. pylori eradication rate: 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin versus 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, there was no evidence of any clinical benefit with respect to dyspeptic symptoms. This study does not support any information for children aged less than 4 years.
Absorption
Ultop is acid labile and is therefore administered orally as enteric-coated granules in hard-gelatin capsules. Absorption of Ultop is rapid, with peak-plasma levels occurring 1-2 hours after the dose. Absorption of Ultop takes place in the small intestine and is usually completed within 3-6 hours. Concomitant intake of food has no influence on the bioavailability. The systemic availability (bioavailability) from a single oral dose of Ultop is approximately 40%. After repeated once-daily administration, the bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3l/kg body weight. Ultop is 97% protein bound.
Biotransformation
Ultop is completely metabolised, by the cytochrome P450 system (CYP). The major part of metabolism is dependent on the polymorphically expressed CYP 2C19 responsible for the formation of hydroxyUltop, the major metabolite in plasma. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of Ultop Sulphone. As a consequence of high affinity of Ultop to CYP 2C19, there is the potential for competitive inhibition and metabolic drug-drug interactions with other substrates for CYP 2C19. However due to low affinity to CYP3A4, Ultop has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition Ultop lacks an inhibitory effect on the main CYP enzymes.
Approximately 3% of the Caucasian population and 15-20% of the Asian population lack a functional CYP 2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of Ultop is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 20mg Ultop the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher, by 3 to 5 times. These findings have no implications for the posology of Ultop.
Elimination
The plasma elimination half life of Ultop is usually shorter than one hour both after single and repeated oral once daily dosing. Ultop is completely eliminated from plasma between doses with no tendency for accumulation during once daily administration. Almost 80% of an oral dose of Ultop is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion.
The AUC of Ultop increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. This time- and dose- dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by Ultop and /or it's metabolites (e.g. the sulphone).
No metabolite has been found to have any effect on gastric acid secretion.
Special Populations
Impaired hepatic function
The metabolism of Ultop in patients with liver dysfunction is impaired, resulting in an increased AUC. Ultop has not shown any tendency to accumulate with once-daily dosing.
Impaired renal function
The pharmacokinetics of Ultop, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function.
Elderly
The metabolism rate of Ultop is somewhat reduced in elderly subjects (75-79 years of age).
Paediatric patients
During treatment with the recommended doses to children from the age of 1 year, similar plasma concentrations were obtained as compared to adults. In children younger than 6 months, clearance of Ultop is low due to low capacity to metabolise Ultop.
Absorption
Omeprazole and omeprazole magnesium are acid labile and are therefore administered orally as enteric-coated granules in capsules or tablets. Absorption of omeprazole is rapid, with peak plasma levels occurring approximately 1-2 hours after dose. Absorption of omeprazole takes place in the small intestine and is usually completed within 3-6 hours. Concomitant intake of food has no influence on the bioavailability. The systemic availability (bioavailability) from a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, the bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight. Omeprazole is 97% plasma protein bound.
Biotransformation
Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. As a consequence of high affinity of omeprazole to CYP2C19, there is a potential for competitive inhibition and metabolic drug-drug interactions with other substrates for CYP2C19. However, due to low affinity to CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. In addition, omeprazole lacks an inhibitory effect on the main CYP enzymes.
Approximately 3% of the Caucasian population and 15-20% of Asian populations lack a functional CYP2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of omeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5 to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher, by 3 to 5 times. These findings have no implications for the posology of omeprazole.
Elimination
The plasma elimination half-life of omeprazole is usually shorter than one hour both after single and repeated oral once-daily dosing. Omeprazole is completely eliminated from plasma between doses with no tendency for accumulation during once-daily administration. Almost 80% of an oral dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion.
Linearity/non-linearity
The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. This time- and dose-dependency is due to a decrease of first pass metabolism and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulfone).
No metabolite has been found to have any effect on gastric acid secretion.
Special populations
Hepatic impairment
The metabolism of omeprazole in patients with liver dysfunction is impaired, resulting in an increased AUC. Omeprazole has not shown any tendency to accumulate with once daily dosing.
Renal impairment
The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with reduced renal function.
Elderly
The metabolism rate of omeprazole is somewhat reduced in elderly subjects (75-79 years of age).
Paediatric population
During treatment with the recommended doses to children from the age of 1 year, similar plasma concentrations were obtained as compared to adults. In children younger than 6 months, clearance of omeprazole is low due to low capacity to metabolise omeprazole.
Ultop has no or negligible influence on the ability to drive or use machines. Adverse drug reactions such as dizziness and visual disturbance may occur. If affected, patients should not drive or operate machinery.
Ultop is not likely to affect the ability to drive or use machines. Adverse drug reactions such as dizziness and visual disturbances may occur. If affected, patients should not drive or operate machinery.
No special requirements for disposal.
No special requirements.
