Ropinirole 0.5 mg Film-Coated Tablets (Actavis UK Ltd)

1. Name Of The Medicinal Product

Ropinirole 0.5 mg Film-Coated Tablets

2. Qualitative And Quantitative Composition

Each film-coated tablet contains ropinirole hydrochloride equivalent to 0.5 mg ropinirole base.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Ropinirole 0.5 mg Film-Coated Tablets are yellow, round (7mm in diameter), biconvex, and embossed with R0.5 on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

Ropinirole is indicated for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome (see Section 5.1).

4.2 Posology And Method Of Administration

Oral use.

Adults

Individual dose titration against efficacy and tolerability is recommended.

Ropinirole should be taken just before bedtime, however the dose can be taken up to 3 hours before retiring. Ropinirole may be taken with food, to improve gastrointestinal tolerance.

Treatment initiation (week 1)

The recommended initial dose is 0.25 mg once daily (administered as above) for 2 days. If this dose is well tolerated the dose should be increased to 0.5 mg once daily for the remainder of week 1.

Therapeutic regimen (week 2 onwards)

Following treatment initiation, the daily dose should be increased until optimal therapeutic response is achieved. The average dose in clinical trials, in patients with moderate to severe Restless Legs Syndrome, was 2.0 mg once a day.

The dose may be increased to 1.0 mg once a day at week 2. The dose may then be increased by 0.5 mg per week over the next two weeks to a dose of 2.0 mg once a day. In some patients, to achieve optimal improvement, the dose may be increased gradually up to a maximum of 4.0 mg once a day. In clinical trials the dose was increased by 0.5 mg each week to 3.0 mg once a day and then by 1.0 mg up to the maximum recommended dose of 4.0 mg once a day as shown in Table 1.

Doses above 4.0 mg once daily have not been investigated in Restless Legs Syndrome patients.

Table 1 - Dose titration

Week	2	3	4	5*	6*	7*
Dose (mg) / once daily	1.0	1.5	2.0	2.5	3.0	4.0

* To achieve optimal improvement in some patients.

The patient's response to ropinirole should be evaluated after 3 months treatment (see Section 5.1). At this time the dose prescribed and the need for continued treatment should be considered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.

Children and Adolescents

Ropinirole is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.

Elderly

The clearance of ropinirole is decreased in patients over 65 years of age. Any increase in dosage should be gradual and titrated against the symptomatic response.

Renal impairment

No dosage adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Severe renal impairment (creatinine clearance < 30ml/min).

Severe hepatic impairment.

4.4 Special Warnings And Precautions For Use

Ropinirole should not be used to treat neuroleptic akathisia, tasikinesia (neuroleptic-induced compulsive tendency to walk), or secondary Restless Legs Syndrome (e.g. caused by renal failure, iron deficiency anaemia or pregnancy).

During treatment with ropinirole, paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed. If this occurs, treatment should be reviewed and dosage adjustment or discontinuation of treatment may be considered.

In Parkinson's disease, ropinirole has been associated uncommonly with somnolence and episodes of sudden sleep onset (see Section 4.8) however in Restless Legs Syndrome, this phenomenon is very rare. Nevertheless, patients must be informed of this phenomenon and advised to exercise caution while driving or operating machines during treatment with ropinirole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Patients with major psychotic disorders should not be treated with dopamine agonists unless the potential benefits outweigh the risks.

Impulse control disorders including pathological gambling and hypersexuality, and increased libido, have been reported in patients treated with dopamine agonists, including ropinirole, principally for Parkinson's disease. Those disorders were reported especially at high doses and were generally reversible upon reduction of the dose or treatment discontinuation. Risk factors such as a history of compulsive behaviours were present in some cases (see section 4.8).

Ropinirole should be administered with caution to patients with moderate hepatic impairment. Undesirable effects should be closely monitored.

Due to the risk of hypotension, patients with severe cardiovascular disease (in particular coronary insufficiency) should be treated with caution.

Ropinirole Film-Coated Tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Ropinirole is principally metabolised by the cytochrome P450 isoenzyme CYP1A2. A pharmacokinetic study (with a ropinirole dose of 2 mg, three times a day) revealed that ciprofloxacin increased the C_max and AUC of ropinirole by 60% and 84% respectively, with a potential risk of adverse events. Hence, in patients already receiving ropinirole, the dose of ropinirole may need to be adjusted when medicinal products known to inhibit CYP1A2, e.g. ciprofloxacin, enoxacin or fluvoxamine, are introduced or withdrawn.

A pharmacokinetic interaction study between ropinirole (at a dose of 2 mg, three times a day) and theophylline, a substrate of CYP1A2, revealed no change in the pharmacokinetics of either ropinirole or theophylline. Therefore, it is not expected that ropinirole will compete with the metabolism of other medicinal products which are metabolised by CYP1A2.

Based on in-vitro data, ropinirole has little potential to inhibit cytochrome P450 at therapeutic doses. Hence, ropinirole is unlikely to affect the pharmacokinetics of other medicinal products, via a cytochrome P450 mechanism.

Smoking is known to induce CYP1A2 metabolism. Therefore, if patients stop or start smoking during treatment with ropinirole, dose adjustment may be required.

Increased plasma concentrations of ropinirole have been observed in patients treated with hormone replacement therapy. In patients already receiving hormone replacement therapy, ropinirole treatment may be initiated in the usual manner. However, it may be necessary to adjust the ropinirole dose, in accordance with clinical response, if hormone replacement therapy is stopped or introduced during treatment with ropinirole.

No pharmacokinetic interaction has been seen between ropinirole and domperidone (a medicinal product used to treat nausea and vomiting) that would necessitate dosage adjustment of either medicinal product. Domperidone antagonises the dopaminergic actions of ropinirole peripherally and does not cross the blood-brain barrier. Hence its value as an anti-emetic in patients treated with centrally acting dopamine agonists

Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and, therefore, concomitant use of these medicinal products with ropinirole should be avoided.

4.6 Pregnancy And Lactation

There are no adequate data from the use of ropinirole in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.

Ropinirole should not be used in nursing mothers as it may inhibit lactation.

4.7 Effects On Ability To Drive And Use Machines

Patients being treated with ropinirole and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such effects have resolved (see also Section 4.4).

4.8 Undesirable Effects

Adverse drug reactions are listed below by system organ class and frequency. Frequencies from clinical trials are determined as excess incidence over placebo and are classed as Very Common (> 1/10) or Common (> 1/100 to < 1/10) or uncommon (> 1/1000 to < 1/100).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Use of ropinirole in Restless Legs Syndrome

In Restless Legs Syndrome clinical trials the most common adverse drug reaction was nausea (approximately 30% of patients). Undesirable effects were normally mild to moderate and experienced at the start of therapy or on increase of dose and few patients withdrew from the clinical studies due to undesirable effects.

Table 2 lists the adverse drug reactions reported for ropinirole in the 12-week clinical trials at

Table 2 - Adverse drug reactions reported in 12-week Restless Legs Syndrome clinical trials (ropinirole n=309, placebo n=307)

Psychiatric Disorders
Common:	Nervousness
Uncommon:	Confusion
Nervous System Disorders
Common:	Syncope, Somnolence, Dizziness (including vertigo)
Vascular Disorders
Uncommon:	Postural hypotension, hypotension
Gastrointestinal Disorders
Very Common:	Vomiting, Nausea
Common:	Abdominal pain
General Disorders and Administration Site Conditions
Common:	Fatigue

Hallucinations were reported uncommonly in the open label long-term studies.

Paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed during treatment with ropinirole.

Management of undesirable effects

Dose reduction should be considered if patients experience significant undesirable effects. If the undesirable effect abates, gradual up-titration can be re-instituted. Anti-nausea medicinal products that are not centrally active dopamine antagonists, such as domperidone, may be used if required.

Other experience with Ropinirole

Ropinirole is also indicated for the treatment of Parkinson's disease. The adverse drug reactions reported in patients with Parkinson's disease on ropinirole monotherapy and adjunct therapy at doses up to 24 mg/day at excess incidence over placebo are described below.

Table 3 - Adverse drug reactions reported in Parkinson's disease clinical trials at doses up to 24 mg/day

Psychiatric Disorders
Common:	Hallucinations, Confusion
Uncommon:	Increased libido
Nervous System Disorders
Very Common:	Syncope, Dyskinesia, Somnolence
Gastrointestinal Disorders
Very Common:	Nausea
Common:	Vomiting, Abdominal pain, Heartburn
General Disorders and Administration Site Conditions
Common:	Leg oedema

Post marketing reports

Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus)

Psychotic reactions (other than hallucinations) including delirium, delusion, paranoia have been reported.

Impulse control disorders including pathological gambling and hypersexuality, and increased libido, have been reported (see section 4.4).

In Parkinson's disease, ropinirole is associated with somnolence and has been associated uncommonly (>1/1,000, <1/100) with excessive daytime somnolence and sudden sleep onset episodes, however, in Restless Legs Syndrome, this phenomenon is very rare (<1/10,000).

Following ropinirole therapy, postural hypotension or hypotension has been reported uncommonly (>1/1,000, <1/100), rarely severe.

Very rare cases of hepatic reactions (<1/10,000), mainly increase of liver enzymes, have been reported.

4.9 Overdose

It is anticipated that the symptoms of ropinirole overdose will be related to its dopaminergic activity. These symptoms may be alleviated by appropriate treatment with dopamine antagonists such as neuroleptics or metoclopramide.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Dopamine agonist ATC code: N04BC04

Mechanism of action

Ropinirole is a non-ergoline D2/D3 dopamine agonist which stimulates striatal dopamine receptors.

Clinical efficacy

Ropinirole Film-coated Tablets should only be prescribed to patients with moderate to severe idiopathic Restless Legs Syndrome. Moderate to severe idiopathic Restless Legs Syndrome is typically represented by patients who suffer with insomnia or severe discomfort in the limbs.

In the four 12-week efficacy studies, patients with Restless Legs Syndrome were randomised to ropinirole or placebo, and the effects on the IRLS scale scores at week 12 were compared to baseline. The mean dose of ropinirole for the moderate to severe patients was 2.0 mg/day. In a combined analysis of moderate to severe Restless Legs Syndrome patients from the four 12-week studies, the adjusted treatment difference for the change from baseline in IRLS scale total score at week 12 Last Observation Carried Forward (LOCF) Intention To Treat population was -4.0 points (95% CI -5.6, -2.4, p<0.0001; baseline and week 12 LOCF mean IRLS points: ropinirole 28.4 and 13.5; placebo 28.2 and 17.4).

A 12-week placebo-controlled polysomnography study in Restless Legs Syndrome patients examined the effect of treatment with ropinirole on periodic leg movements of sleep. A statistically significant difference in the periodic leg movements of sleep was seen between ropinirole and placebo from baseline to week 12.

Although sufficient data is not available to adequately demonstrate the long term efficacy of ropinirole in Restless Legs Syndrome (see Section 4.2), in a 36-week study, patients who continued on ropinirole demonstrated a significantly lower relapse rate compared with patients randomised to placebo (33% versus 58%, p=0.0156).

A combined analysis of data from moderate to severe Restless Legs Syndrome patients, in the four 12-week placebo-controlled studies, indicated that ropinirole-treated patients reported significant improvements over placebo on the parameters of the Medical Outcome Study Sleep Scale (scores on 0-100 range except sleep quantity). The adjusted treatment differences between ropinirole and placebo were: sleep disturbance (-15.2, 95% CI -19.37, -10.94; p<0.0001), sleep quantity (0.7 hours, 95% CI 0.49, 0.94; p<0.0001), sleep adequacy (18.6, 95% CI 13.77, 23.45; p<0.0001) and daytime somnolence (-7.5, 95% CI -10.86, -4.23; p<0.0001).

A rebound phenomenon following discontinuation of ropinirole treatment (end of treatment rebound) cannot be excluded. In clinical trials, although the average IRLS total scores 7-10 days after withdrawal of therapy were higher in ropinirole-treated patients than in placebo-treated patients, the severity of symptoms following withdrawal of therapy generally did not exceed the baseline assessment in ropinirole-treated patients.

In clinical studies most patients were of Caucasian origin.

Study of the effect of ropinirole on cardiac repolarisation

A thorough QT study conducted in male and female healthy volunteers who received doses of 0.5, 1, 2 and 4 mg of ropinirole film-coated (immediate release) tablets once daily showed a maximum increase of the QT interval duration at the 1mg dose of 3.46 milliseconds (point estimate) as compared to placebo. The upper bound of the one sided 95% confidence interval for the largest mean effect was less than 7.5 milliseconds. The effect of ropinirole at higher doses has not been systematically evaluated.

The available clinical data from a thorough QT study do not indicate a risk of QT prolongation at doses of ropinirole up to 4 mg/day.

5.2 Pharmacokinetic Properties

Absorption

The bioavailability of ropinirole is about 50% (36% to 57%), with C_max reached on average 1.5 hours after the dose. A high fat meal decreases the rate of absorption of Ropinirole, as shown by a delay in median T_max by 2.6 hours and an average 25% decrease in C_max.

Distribution

Plasma protein binding of ropinirole is low (10 - 40%). Consistent with its high lipophilicity, ropinirole exhibits a large volume of distribution (approx. 7 l/kg).

Metabolism

Ropinirole is primarily cleared by the cytochrome P450 enzyme, CYP1A2, and its metabolites are mainly excreted in the urine. The major metabolite is at least 100 times less potent than ropinirole in animal models of dopaminergic function.

Elimination

Ropinirole is cleared from the systemic circulation with an average elimination half-life of approximately 6 hours. No change in the oral clearance of ropinirole is observed following single and repeated oral administration. Wide inter-individual variability in the pharmacokinetic parameters has been observed.

Linearity

The pharmacokinetics of ropinirole are linear overall (C_max and AUC) in the therapeutic range between 0.25 mg and 4 mg, after a single dose and after repeated dosing.

Population-related characteristics

In patients over 65 years of age, a reduction in the systemic clearance of ropinirole by about 30% is possible.

In patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min), no change in the pharmacokinetics of ropinirole is observed. No data is available in patients with severe renal impairment.

Paediatric population

Limited pharmacokinetic data obtained in adolescents (12-17 years, n=9) showed that the systemic exposure following single doses of 0.125 mg and 0.25 mg was similar to that observed in adults (see also section 4.2; subparagraph “Children and adolescents).

5.3 Preclinical Safety Data

Toxicology: The toxicology profile is principally determined by the pharmacological activity of the drug: behavioural changes, hypoprolactinaemia, decrease in blood pressure and heart rate, ptosis and salivation. In the albino rat only, retinal degeneration was observed in a long term study at a high dose (50 mg/kg), probably associated with an increased exposure to light.

Genotoxicity: Genotoxicity was not observed in the usual battery of in vitro and in vivo tests.

Carcinogenicity: From two-year studies conducted in the mouse and rat at dosages up to 50 mg/kg/day there was no evidence of any carcinogenic effect in the mouse. In the rat, the only drug-related lesions were Leydig cell hyperplasia and testicular adenoma resulting from the hypoprolactinaemic effect of ropinirole. These lesions are considered to be a species specific phenomenon and do not constitute a hazard with regard to the clinical use of ropinirole.

Reproductive Toxicity: Administration of ropinirole to pregnant rats at maternally toxic doses resulted in decreased foetal body weight at 60 mg/kg/day (approximately 15 times the AUC at the maximum dose in humans), increased foetal death at 90 mg/kg/day (approximately 25 times the AUC at the maximum dose in humans) and digit malformations at 150 mg/kg/day (approximately 40 times the AUC at the maximum dose in humans). There were no teratogenic effects in the rat at 120 mg/kg/day (approximately 30 times the AUC at the maximum dose in humans) and no indication of an effect on development in the rabbit.

Safety Pharmacology: In vitro studies have shown that ropinirole inhibits hERG-mediated currents. The IC₅₀ is 5-fold higher than the expected maximum plasma concentration in patients treated at the highest recommended dose (4 mg/day), see section 5.1.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core:

Lactose monohydrate

Microcrystalline cellulose

Pregelatinised starch

Magnesium stearate

Film coating:

Opadry II 85F32111 (Polyvinyl alcohol, Titanium dioxide, Macrogol 3350, Talc, Iron oxide yellow)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Do not store above 25°C

Store in the original package in order to protect from light

HDPE tablet containers only:

Keep the container tightly closed in order to protect from moisture

6.5 Nature And Contents Of Container

Aluminium/Aluminium blister or induction sealed HDPE tablet containers of 2, 5, 7, 10, 12, 14, 20, 21, 28, 30, 50, 56, 60, 84, 100, 126 and 210 tablets.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Caduceus Pharma Limited

6^th Floor, 94 Wigmore Street,

London W1U 3RF

UK

8. Marketing Authorisation Number(S)

PL 24668/0079

9. Date Of First Authorisation/Renewal Of The Authorisation

21/01/2011

10. Date Of Revision Of The Text

25/03/2011

Levofloxacin 500 mg Film-coated Tablets

1. Name Of The Medicinal Product

Levofloxacin 500 mg Film-coated Tablets

2. Qualitative And Quantitative Composition

Each film coated tablet contains 500 mg of levofloxacin as active substance corresponding to 512.46 mg of levofloxacin hemihydrate.

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Film-coated tablet

For 500 mg tablets: Pink coloured, capsule shaped, biconvex, film coated tablet with break line on both sides. Debossed 'L' and 'V' either side of the break line on one face.

The tablets can be divided into equal halves.

4. Clinical Particulars

4.1 Therapeutic Indications

In adults with infections of mild or moderate severity, Levofloxacin Tablets are indicated for the treatment of the following infections when due to levofloxacin-susceptible microorganisms: (see section 5.1)

• Acute sinusitis (adequately diagnosed according to national and/or local guidelines on the treatment of respiratory tract infections, and when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection or when these have failed to resolve the infection),

• Acute exacerbations of chronic bronchitis (adequately diagnosed according to national and/or local guidelines on the treatment of respiratory tract infections, and when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection or when these have failed to resolve the infection),

• Community-acquired pneumonia (when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection),

• For 250mg only: Uncomplicated urinary tract infections

• Complicated urinary tract infections (including pyelonephritis)

• Chronic bacterial prostatitis.

• Skin and soft tissue infections.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology And Method Of Administration

Levofloxacin Tablets are administered once or twice daily. The dosage depends on the type and severity of the infection and the sensitivity of the presumed causative pathogen.

Treatment time

The duration of therapy varies according to the course of the disease (see table below). As with antibiotic therapy in general, administration of Levofloxacin Tablets should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.

Method of administration

Levofloxacin Tablets should be swallowed whole and with sufficient amount of liquid. The tablets may be taken during meals or between meals. Levofloxacin Tablets should be taken at least two hours before iron salts, antacids and sucralfate administration since reduction of absorption can occur (see section 4.5).

The following dose recommendations can be given for Levofloxacin Tablets:

Dosage in patients with normal renal function

(creatinine clearance > 50 ml/min)

Indication	Daily dose regimen (according to severity)	Duration of treatment
Acute sinusitis	500 mg once daily	10 - 14 days
Acute exacerbations of chronic bronchitis	250 to 500 mg once daily	7 - 10 days
Community-acquired pneumonia	500 mg once or twice daily	7 - 14 days
Uncomplicated urinary tract infections	250 mg once daily	3 days
Complicated urinary tract infections including pyelonephritis	250 mg once daily1	7 - 10 days
Chronic bacterial prostatitis	500 mg once daily	28 days
Skin and soft tissue infections	250 mg once daily or 500 mg once or twice daily2	7 - 14 days

^1,2 Consideration should be given to increasing the dose in cases of severe infection and special attention should be paid to available information on resistance to levofloxacin before commencing therapy.

¹ Because of the increasing E.coli resistance the dose 500 mg/day should be considered.

² Because of the increasing Staphylococcus resistance the dose 500 mg twice daily should be considered.

Special Populations

Impaired renal function (creatinine clearance

Creatinine clearance	Dosage regimen
250 mg/24 h	500 mg/24 h	500 mg/12 h
First dose: 250 mg	First dose: 500 mg	First dose: 500 mg
50-20 ml/min	Then:125 mg/24h	Then: 250 mg/24 h	Then:250 mg/12 h
19-10 ml/min	Then: 125 mg/48 h	Then: 125 mg/24 h	Then:125 mg/12 h
< 10 ml/min (including haemodialysis and CAPD)1	Then: 125 mg/48 h	Then: 125 mg/24 h	Then:125 mg/24 h

¹ No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Impaired liver function

No adjustment of dosage is required since levofloxacin is not metabolised to any relevant extent by the liver and is mainly excreted by the kidneys.

Dosage in elderly

No adjustment of dosage is required in the elderly, other than that imposed by consideration of renal function (see section 4.4 QT interval prolongation).

In children

Levofloxacin is contraindicated in children and growing adolescents (less than 18 years of age) (see section 4.3).

4.3 Contraindications

Levofloxacin Tablets must not be used:

• in patients hypersensitive to levofloxacin or other quinolones or any of the excipients,

• in patients with epilepsy,

• in patients with history of tendon disorders related to fluoroquinolone administration,

• in children or growing adolescents (up to age of 18)

• during pregnancy,

• in breast-feeding women.

4.4 Special Warnings And Precautions For Use

In the most severe cases of pneumococcal pneumonia Levofloxacin Tablets may not be the optimal therapy.

Nosocomial infections due to P. aeruginosa may require combination therapy.

Methicillin-resistant Staphylococcus aureus (MRSA)

Levofloxacin is not effective against infections caused by MRSA (see section 5.1). In infections suspicious for MRSA levofloxacin should be combined with an agent approved to treat MRSA infections.

Tendinitis and tendon rupture

Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to tendon rupture. The risk of tendinitis and tendon rupture is increased in the elderly and in patients using corticosteroids. Close monitoring of these patients is therefore necessary if they are prescribed Levofloxacin Tablets. All patients should consult their physician if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with Levofloxacin Tablets must be halted immediately, and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon.

Clostridium difficile-associated disease

Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with Levofloxacin Tablets, may be symptomatic of Clostridium difficile-associated disease, the most severe form of which is pseudomembranous enterocolitis. If pseudomembranous enterocolitis is suspected, Levofloxacin Tablets must be stopped immediately and patients should be treated with supportive measures and specific therapy without delay (e.g. oral metronidazole or vancomycin). Products inhibiting the peristalsis are contraindicated in this clinical situation.

Patients predisposed to seizures

Levofloxacin Tablets are contraindicated in patients with a history of epilepsy and, as with other quinolones, should be used with extreme caution in patients predisposed to seizures, such as patients with pre-existing central nervous system damage; concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs or with drugs which lower the cerebral seizure threshold, such as theophylline (see section 4.5). In case of convulsive seizures, treatment with levofloxacin should be discontinued.

Patients with G-6- phosphate dehydrogenase deficiency

Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents, and so levofloxacin should be used with caution.

Patients with renal impairment

Since levofloxacin is excreted mainly by the kidneys, the dose of Levofloxacin Tablets should be adjusted in patients with renal impairment. (see section 4.2).

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema to anaphylactic shock), occasionally following the initial dose (see section 4.8). Patients should discontinue treatment immediately and contact their physician or an emergency physician, who will initiate appropriate emergency measures.

Hypoglycemia

As with all quinolones, hypoglycemia has been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glibenclamide) or with insulin. In these diabetic patients, careful monitoring of blood glucose is recommended. (see section 4.8).

Prevention of photosensitisation

Although photosensitisation is very rare with levofloxacin, it is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), in order to prevent photosensitisation.

Patients treated with Vitamin K antagonists

Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs are given concomitantly (see section 4.5).

Psychotic reactions

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare cases these have progressed to suicidal thoughts and self-endangering behaviour- sometimes after only a single dose of levofloxacin (see section 4.8). In the event that the patient develops these reactions, levofloxacin should be discontinued and appropriate measures instituted. Caution is recommended if levofloxacin is to be used in psychotic patients or in patients with a history of psychiatric disease.

Cardiac disorders

Caution should be taken when using fluoroquinolones, including levofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:

- congenital long QT syndrome

-concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides).

- uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia)

- elderly

- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

(see section 4.2 Elderly, section 4.5, section 4.8, section 4.9).

Peripheral neuropathy

Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving fluoroquinolones, including levofloxacin, which can be rapid in its onset. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversible condition.

Opiates

In patients treated with levofloxacin, determination of opiates in urine may give false-positive results. It may be necessary to confirm positive opiate screens by a more specific method.

Hepatobiliary disorders

Cases of hepatic necrosis up to life threatening hepatic failure have been reported with levofloxacin, primarily in patients with severe underlying diseases, e.g. sepsis (see section 4.8). Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Effect of other medicinal products on levofloxacin

Iron salts, magnesium- or aluminium-containing antacids

Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or aluminium-containing antacids are administered concomitantly. It is recommended that preparations containing divalent or trivalent cations such as iron salts, or magnesium- or aluminium-containing antacids should not be taken 2 hours before or after Levofloxacin Tablets administration (see section 4.2). No interaction was found with calcium carbonate.

Sucralfate

The bioavailability of Levofloxacin Tablets is significantly reduced when administered together with sucralfate. If the patient is to receive both sucralfate and Levofloxacin Tablets, it is best to administer sucralfate 2 hours after the Levofloxacin Tablets administration (see section 4.2).

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs

No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. However a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other agents which lower the seizure threshold.

Levofloxacin concentrations were about 13 % higher in the presence of fenbufen than when administered alone.

Probenecid and cimetidine

Probenecid and cimetidine had a statistically significant effect on the elimination of levofloxacin. The renal clearance of levofloxacin was reduced by cimetidine (24 %) and probenecid (34 %). This is because both drugs are capable of blocking the renal tubular secretion of levofloxacin. However, at the tested doses in the study, the statistically significant kinetic differences are unlikely to be of clinical relevance.

Caution should be exercised when levofloxacin is coadministered with drugs that effect the tubular renal secretion such as probenecid and cimetidine, especially in renally impaired patients.

Effect of levofloxacin on other medicinal products

Ciclosporin

The half-life of ciclosporin was increased by 33 % when coadministered with levofloxacin.

Vitamin K antagonists

Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists (see section 4.4).

Drugs known to prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotic). (See section 4.4 ).

Other forms of interactions

Meals

There is no clinically relevant interaction with food. Levofloxacin Tablets may therefore be administered regardless of food intake.

Other relevant information

Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with the following drugs:

- calcium carbonate

- digoxin

- glibenclamide

- ranitidine.

4.6 Pregnancy And Lactation

Pregnancy

There are no data with respect to the use of levofloxacin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). In juvenile and prenatal animals exposed to quinolones, effects on immature cartilage have been observed; thus, it cannot be excluded that the drug could cause damage to articular cartilage in the human immature organism / fetus (see section 5.3). The product is therefore contraindicated during pregnancy.

Lactation

There is insufficient information with respect to the excretion of levofloxacin in human and/or animal milk. In the absence of these data and given the potential risk of articular damage, levofloxacin is contraindicated during breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

Some undesirable effects (e.g. dizziness/vertigo, drowsiness, visual disturbances) may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).

4.8 Undesirable Effects

The information given below is based on data from clinical studies in more than 5000 patients and on extensive post marketing experience.

The adverse reactions are described according to the MedDRA system organ class below.

Frequencies are defined using the following convention: very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Cardiac disorders

Rare: Tachycardia

Not Known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), Electrocardiogram QT prolonged (see section 4.4 and section 4.9)

Blood and lymphatic system disorders

Uncommon : Leukopenia, eosinophilia

Rare : Thrombocytopenia, neutropenia

Very rare : Agranulocytosis

Not Known : Pancytopenia, haemolytic anaemia

Nervous system disorders

Uncommon : Dizziness, headache, somnolence

Rare : Convulsion, tremor, paraesthesia,

Very rare: sensory or sensorimotor peripheral neuropathy, dysgeusia including ageusia, parosmia including anosmia

Eye disorders

Very rare: Visual disturbance

Ear and Labyrinth disorders

Uncommon: Vertigo

Very rare: Hearing impaired

Not known: Tinnitus

Respiratory, thoracic and mediastinal disorders

Rare: Bronchospasm, dyspnoea

Very rare: Pneumonitis allergic

Gastrointestinal disorders

Common: Diarrhoea, nausea

Uncommon: Vomiting, abdominal pain, dyspepsia, flatulence, constipation

Rare: Diarrhoea -haemorrhagic which in very rare cases may be indicative of enterocolitis, including pseudomembranous colitis

Renal and urinary disorders

Uncommon: Blood creatinine increased

Very rare: Renal failure acute (e.g. due to nephritis interstitial)

Skin and subcutaneous tissue disorders

Uncommon: Rash, pruritus

Rare: Urticaria

Very rare: Angioneurotic oedema, photosensitivity reaction

Not Known: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, hyperhidrosis

Mucocutaneous reactions may sometimes occur even after the first dose

Musculoskeletal and Connective tissue disorders

Rare: Tendon disorder (see section 4.4) including tendinitis (e.g. Achilles tendon), arthralgia, myalgia

Very rare: Tendon rupture (see section 4.4). This undesirable effect may occur within 48 hours of starting treatment and may be bilateral, muscular weakness which may be of special importance in patients with myasthenia gravis

Not Known: Rhabdomyolysis

Metabolism and nutrition disorders

Uncommon: Anorexia

Very rare: Hypoglycemia, particularly in diabetic patients (see section 4.4)

Infections and infestations

Uncommon: Fungal infection (and proliferation of other resistant microorganisms)

Vascular disorders

Rare: Hypotension

General disorders and administration site conditions

Uncommon: Asthenia

Very rare: Pyrexia

Not known: Pain (including pain in back, chest, and extremities)

Immune system disorders

Very rare: Anaphylactic shock (see section 4.4)

Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose

Not known: Hypersensitivity (see section 4.4)

Hepatobiliary disorders

Common: Hepatic enzyme increased (ALT/AST, alkaline phosphatase, GGT)

Uncommon: Blood bilirubin increased

Very rare: Hepatitis

Not known: Jaundice and severe liver injury, including cases with acute liver failure, have been reported with levofloxacin, primarily in patients with severe underlying diseases (see section 4.4).

Psychiatric disorders

Uncommon: Insomnia, nervousness

Rare: Psychotic disorder, Depression, confusional state, agitation, anxiety

Very rare: Psychotic reactions with self-endangering behaviour including suicidal ideation or acts (see section 4.4), hallucination

Other undesirable effects which have been associated with fluoroquinolone administration include:

• extrapyramidal symptoms and other disorders of muscular coordination,

• hypersensitivity vasculitis,

• attacks of porphyria in patients with porphyria.

4.9 Overdose

According to toxicity studies in animals or clinical pharmacology studies performed with supra-therapeutic doses, the most important signs to be expected following acute overdosage of levofloxacin are central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures, increases in QT interval as well as gastro-intestinal reactions such as nausea and mucosal erosions.

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Antacids may be used for protection of gastric mucosa. Haemodialysis, including peritoneal dialysis and CAPD, are not effective in removing levofloxacin from the body. No specific antidote exists.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antiifectives for systemic use - Antibacterials for systemic use - Quinolone antibasterials - Fluoroquinolones

ATC code: J01MA12

Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-) enantiomer of the racemic drug substance ofloxacin.

Mechanism of action

As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA-gyrase complex and topoisomerase IV.

PK/PD releationship

The degree of the bactericidal activity of levofloxacin depends on the ratio of the maximum concentration in serum (C_max) or the area under the curve (AUC) and the minimal inhibitory concentration (MIC).

Mechanism(s) of resisance

The main mechanism of resistance is due to a gyr-A mutation. In vitro there is a cross-resistance between levofloxacin and other fluoroquinolones.

Due to the mechanism of action, there is generally no cross-resistance between levofloxacin and other classes of antibacterial agents.

Breakpoints

The EUCAST recommended MIC breakpoints for levofloxacin, separating susceptible from intermediately susceptible organisms and intermediately susceptible from resistant organisms are presented in the below table for MIC testing (mg/L).

EUCAST clinical MIC breakpoints for levofloxacin (2006-06-20):

Pathogen	Susceptible	Resistant
Enterobacteriacae		>2 mg/L
Pseudomonas spp.		>2 mg/L
Acinetobacter spp.		>2 mg/L
Staphylococcus spp.		>2 mg/L
S.pneumoniae1		>2 mg/L
Streptococcus A,B,C,G		>2 mg/L
H.influenzae M.catarrhalis 2		>1 mg/L
Non-species related breakpoints 3		>2 mg/L

¹ the S/I-breakpoint was increased from 1.0 to 2.0 to avoid dividing the wild type MIC distribution. The breakpoints relate to high dose therapy.

² Strains with MIC values above the S/I breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory.

³ Non-species related breakpoints have been determined mainly on the basis of pharmacokinetic/pharmacodynamic data and are independent of MIC distributions of specific species. They are for use only for species that have not been given a species-specific breakpoint and are not for use with species where susceptibility testing is not recommended or for which there is insufficient evidence that the species in question is a good target (Enterococcus, Neisseria, Gram negative anaerobes)

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Commonly susceptible species

Aerobic Gram-positive bacteria

Staphylococcus aureus* methicillin-susceptible Coagulase negative meticillin-susceptible Staphylococcus, including staphylococcus saprophyticus Streptococci

Aerobic Gram- negative bacteria

Eikenella corrodens Haemophilus influenzae * Haemophilus para-influenzae * Klebsiella oxytoca Klebsiella pneumoniae * Legionella pneumophila* Moraxella catarrhalis * Pasteurella multocida Proteus vulgaris Providencia rettgeri

Anaerobic bacteria

Clostridium perfringens Fusobacterium Prevotella($), Propionibacterium

Other

Chlamydophila pneumoniae * Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae * Mycoplasma hominis Ureaplasma urealyticum

Species for which acquired resistance may be a problem

Aerobic Gram-positive bacteria

Enterococcus faecalis* Staphylococcus aureus methicillin-resistant Staphylococcus coagulase negative methicillin-resistant

Aerobic Gram- negative bacteria

Acinetobacter baumannii * Citrobacter freundii * Enterobacter aerogenes Enterobacter agglomerans Enterobacter cloacae * Escherichia coli * Morganella morganii * Proteus mirabilis * Providencia stuartii Pseudomonas aeruginosa* Serratia marcescens *

Anaerobic bacteria

Peptostreptococcus

Naturally resistant species

Aerobic Gram-positive bacteria

Enterococcus faecium

Aerobic Gram-negative bacteria

Burkholderia cepacia

Anaerobic bacteria

Bacteroides Clostridium difficile

* Clinical efficacy has been demonstrated for susceptible isolates in the approved clinical indications.

$ natural intermediate susceptibility

Other information

Nosocomial infections due to P. aeruginosa may require combination therapy.

5.2 Pharmacokinetic Properties

Absorption

Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma concentrations being obtained within 1 h. The absolute bioavailability is approximately 100 %. Food has little effect on the absorption of levofloxacin.

Distribution

Approximately 30 - 40 % of levofloxacin is bound to serum protein. 500 mg once daily multiple dosing with levofloxacin showed negligible accumulation. There is modest but predictable accumulation of levofloxacin after doses of 500 mg twice daily. Steady-state is achieved within 3 days.

Penetration into tissues and body fluids:

Penetration into Bronchial Mucosa, Epithelial Lining Fluid (ELF)

Maximum levofloxacin concentrations in bronchial mucosa and epithelial lining fluid after 500 mg p.o. were 8.3 μg/g and 10.8 μg/ml respectively. These were reached approximately one hour after administration.

Penetration into Lung Tissue

Maximum levofloxacin concentrations in lung tissue after 500 mg p.o. were approximately 11.3 μg/g and were reached between 4 and 6 hours after administration. The concentrations in the lungs consistently exceeded those in plasma.

Penetration into Blister Fluid

Maximum levofloxacin concentrations of about 4.0 and 6.7 μg/ml in the blister fluid were reached 2 - 4 hours after administration following 3 days dosing at 500 mg once or twice daily, respectively.

Penetration into Cerebro-Spinal Fluid

Levofloxacin has poor penetration into cerebro-spinal fluid.

Penetration into prostatic tissue

After administration of oral 500mg levofloxacin once a day for three days, the mean concentrations in prostatic tissue were 8.7 µg/g, 8.2 µg/g and 2.0 µg/g respectively after 2 hours, 6 hours and 24 hours; the mean prostate/plasma concentration ratio was 1.84.

Concentration in urine

The mean urine concentrations 8 - 12 hours after a single oral dose of 150 mg, 300 mg or 500 mg levofloxacin were 44 mg/L, 91 mg/L and 200 mg/L, respectively.

Biotransformation

Levofloxacin is metabolised to a very small extent, the metabolites being desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites account for < 5 % of the dose excreted in urine. Levofloxacin is stereochemically stable and does not undergo chiral inversion.

Elimination

Following oral and intravenous administration of levofloxacin, it is eliminated relatively slowly from the plasma (t_½: 6 - 8 h). Excretion is primarily by the renal route > 85 % of the administered dose).

There are no major differences in the pharmacokinetics of levofloxacin following intravenous and oral administration, suggesting that the oral and intravenous routes are interchangeable.

Linearity

Levofloxacin obeys linear pharmacokinetics over a range of 50 to 600 mg.

Subjects with renal insufficiency

The pharmacokinetics of levofloxacin are affected by renal impairment. With decreasing renal function renal elimination and clearance are decreased, and elimination half-lives increased as shown in the table below:

Clcr [ml/min]	< 20	20 - 40	50 - 80
ClR [ml/min]	13	26	57
t1/2 [h]	35	27	9

Elderly subjects

There are no significant differences in levofloxacin kinetics between young and elderly subjects, except those associated with differences in creatinine clearance.

Gender differences

Separate analysis for male and female subjects showed small to marginal gender differences in levofloxacin pharmacokinetics. There is no evidence that these gender differences are of clinical relevance.

5.3 Preclinical Safety Data

During repeat-dose studies, common observations included reduced food consumption and minor alterations in haematological and biochemical parameters at 200 mg/kg/day in the rat and reduced body weight, saliv

Boots Glycerin & Blackcurrant Linctus (Boots Company plc)

Glycerin and Blackcurrant Linctus (Boots Company plc)

(Glycerol, Sucrose)

Helps relieve sore throats and dry, tickly coughs

200 ml e

Read all of this label for full instructions.

Uses:

A linctus to relieve irritating tickly, dry coughs and sore throats.

Before you take this medicine

Do not take:

• If you are allergic or intolerant to any of the ingredients



• If you have an intolerance to some sugars, unless your doctor tells you to (this medicine contains glucose)

People with diabetes should take into account the carbohydrate content of this medicine (6.9 g per 10 ml).

You can take this medicine if your are pregnant or breastfeeding.

How to take this medicine

Check the cap seal is not broken before first use. If it is, do not take the medicine.

Adults and children of 5 years and over: Two 5 ml spoonfuls. Swallow this amount 3 or 4 times a day.

Children of 1 to 4 years: One 5 ml spoonful. Give this amount to your child to swallow 3 or 4 times a day.

Do not give to children under 1 year.

If symptoms do not go away talk to your pharmacist or doctor.

If you take or give too much: Talk to a pharmacist or doctor.

Possible side effects

This medicine is not expected to cause any side effects.

If you notice any side effect, please tell your pharmacist or doctor.

Keep all medicines out of the sight and reach of children.

Use by the date on the label edge.

Active ingredients

Each 10 ml of liquid contains Glycerol 1.5 ml, Sucrose 3.4 g.

Also contains: glucose (1.6 g), purified water, citric acid, sodium benzoate, anthocyanin, flavour (blackcurrant flavour and blackcurrant juice).

PL 00014/0307

Text prepared 12/07

Manufactured by the Marketing Authorisation holder

The Boots Company PLC

Nottingham

NG2 3AA

If you need more advice ask your pharmacist.

BTC19702 vD 13/06/08

esomeprazole Oral, Intravenous

es-oh-MEP-ra-zole SOE-dee-um

Commonly used brand name(s)

In the U.S.

• Nexium I.V.

Available Dosage Forms:

• Powder for Solution

Pharmacologic Class: Esomeprazole

Uses For esomeprazole

Esomeprazole injection is used to treat conditions where there is too much acid in the stomach. It is used for the short-term treatment (up to 10 days) of gastroesophageal reflux disease (GERD) with erosive esophagitis in adults and children 1 month of age and older. GERD is a condition where the acid in the stomach washes back up into the esophagus.

Esomeprazole is a proton pump inhibitor (PPI). It works by decreasing the amount of acid that is produced by the stomach.

esomeprazole is available only with your doctor's prescription.

Before Using esomeprazole

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For esomeprazole, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to esomeprazole or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of esomeprazole injection in children greater than 1 month of age. However, safety and efficacy have not been established in infants younger than 1 month of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of esomeprazole injection in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving esomeprazole, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using esomeprazole with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rilpivirine

Using esomeprazole with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atazanavir


• Citalopram


• Clopidogrel


• Dasatinib


• Erlotinib


• Methotrexate


• Mycophenolate Mofetil


• Nelfinavir


• Nilotinib

Using esomeprazole with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cranberry


• Posaconazole


• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of esomeprazole. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Osteoporosis (thinning of the bones)—Use with caution. May make this condition worse.

Proper Use of esomeprazole

A nurse or other trained health professional will give you or your child esomeprazole in a clinic or hospital. esomeprazole is given through a needle placed in one of your veins.

Your doctor will give you a few doses of esomeprazole until your condition improves, and then switch you to an oral medicine that works the same way. If you have any concerns about this, talk to your doctor.

Precautions While Using esomeprazole

It is important that your doctor check the progress of you or your child at regular visits. If your or your child's condition does not improve, or if it becomes worse, check with your doctor.

esomeprazole may cause atrophic gastritis (inflammation in the stomach). This has happened in patients who used a similar medicine called omeprazole (Prilosec®) for a long time. Check with your doctor right away if you or your child have a burning feeling in the chest or stomach; indigestion; stomach upset; or tenderness in the stomach area.

Esomeprazole injection may increase your risk of having fractures of the hip, wrist, and spine. This is more likely if you are 50 years of age and older, if you receive high doses of esomeprazole, or use it for one year or more.

Make sure any doctor or dentist who treats you knows that you or your child are using esomeprazole. esomeprazole may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

esomeprazole Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Incidence not known

• Blistering, peeling, or loosening of the skin


• bloating


• chills


• cough


• darkened urine


• difficulty with swallowing


• dizziness


• fast heartbeat


• fever


• hives


• indigestion


• itching


• joint or muscle pain


• loss of appetite


• pains in the stomach, side, or abdomen, possibly radiating to the back


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• red, irritated eyes


• red skin lesions, often with a purple center


• shortness of breath


• skin rash


• sore throat


• sores, ulcers, or white spots in the mouth or on the lips


• tightness in the chest


• unusual tiredness or weakness


• vomiting


• wheezing


• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Acid or sour stomach


• belching


• heartburn


• stomach discomfort, upset, or pain

Less common

• Burning, itching, redness, skin rash, swelling, or soreness at the injection site


• diarrhea


• difficulty having a bowel movement (stool)


• dryness of the mouth


• feeling of constant movement of self or surroundings


• gas


• headache


• lightheadedness


• nausea


• pain or tenderness around the eyes and cheekbones


• sensation of spinning


• sneezing


• stuffy or runny nose


• wheezing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: esomeprazole Oral, Intravenous side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

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More esomeprazole Oral, Intravenous resources

• Esomeprazole Oral, Intravenous Side Effects (in more detail)
• Esomeprazole Oral, Intravenous Use in Pregnancy & Breastfeeding
• Esomeprazole Oral, Intravenous Drug Interactions
• Esomeprazole Oral, Intravenous Support Group
• 54 Reviews for Esomeprazole Oral, Intravenous - Add your own review/rating

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