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.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

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

Compare esomeprazole Oral, Intravenous with other medications

• Barrett's Esophagus
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• GERD
• Helicobacter Pylori Infection
• NSAID-Induced Gastric Ulcer
• Pathological Hypersecretory Conditions
• Zollinger-Ellison Syndrome

Touro CC-LD

Generic Name: dextromethorphan, guaifenesin, and pseudoephedrine (dex troe meth OR fan, gwye FEN e sin, soo doe e FED rin)

Brand Names: Altarussin CF, Ambifed-G DM, Relacon-DM NR, Robitussin Cold and Cough, Robitussin Pediatric Cough and Decongestant, Suda-Tussin DM, Touro CC, Touro CC-LD, Tussafed-LA

What is Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

Guaifenesin is an expectorant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth.

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of dextromethorphan, guaifenesin, and pseudoephedrine is used to treat stuffy nose, sinus congestion, cough, and chest congestion caused by the common cold or flu.

Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

Dextromethorphan, guaifenesin, and pseudoephedrine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Do not use any other over-the-counter cough, cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains a decongestant, expectorant, or cough suppressant. Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

What should I discuss with my healthcare provider before using Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Do not use this medicine if you are allergic to dextromethorphan, guaifenesin, or pseudoephedrine.

Before taking this medicine, tell your doctor if you are allergic to any drugs or if you have emphysema or chronic bronchitis. You may not be able to use this medication, or you may need a dosage adjustment or special tests during treatment.

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. This medication may pass into breast milk and could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Take the medication with food if it upsets your stomach. Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking or opening the pill would cause too much of the drug to be released at one time. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

Store this medicine at room temperature, away from heat, light, and moisture.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling restless or nervous.

What should I avoid while taking Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with cough or cold medicine can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cough, cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains a decongestant, expectorant, or cough suppressant.

Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  confusion, hallucinations; or

  
  


• 
  

  slow, shallow breathing.

  
  

Less serious side effects may include:

• 
  

  dizziness or headache,

  
  


• 
  

  a rash, or

  
  


• 
  

  nausea, vomiting, or stomach upset.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Touro CC-LD (dextromethorphan, guaifenesin, and pseudoephedrine)?

Before taking dextromethorphan, guaifenesin, and pseudoephedrine, tell your doctor if you are using any of the following drugs:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  cinacalcet (Sensipar);

  
  


• 
  

  darifenacin (Enablex);

  
  


• 
  

  imatinib (Gleevec);

  
  


• 
  

  quinidine (Quinaglute, Quinidex);

  
  


• 
  

  ranolazine (Ranexa)

  
  


• 
  

  ritonavir (Norvir);

  
  


• 
  

  sibutramine (Meridia);

  
  


• 
  

  terbinafine (Lamisil);

  
  


• 
  

  medicines to treat high blood pressure; or

  
  


• 
  

  antidepressant medications such as amitriptyline (Elavil, Etrafon), bupropion (Wellbutrin, Zyban), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Janimine, Tofranil), paroxetine (Paxil), sertraline (Zoloft), and others.

  
  

This list is not complete and there may be other drugs that can interact with dextromethorphan, guaifenesin, and pseudoephedrine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Touro CC-LD resources

• Touro CC-LD Use in Pregnancy & Breastfeeding
• Touro CC-LD Drug Interactions
• Touro CC-LD Support Group
• 0 Reviews for Touro CC-LD - Add your own review/rating

• Ambi 60/580/30 Controlled-Release and Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Dextromethorphan/Guaifenesin/Pseudoephedrine MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Touro CC-LD with other medications

• Cough and Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about dextromethorphan, guaifenesin, and pseudoephedrine.

Alupent

Generic Name: Metaproterenol Sulfate
Class: Selective beta-2-Adrenergic Agonists
VA Class: RE102
CAS Number: 5874-97-5

Introduction

Bronchodilator; less selective than relatively selective β₂-adrenergic agonists (e.g., albuterol).^{b c f h i j k}

Uses for Alupent

Bronchospasm in Asthma

Symptomatic management of bronchospasm in patients with reversible, obstructive airway disease (e.g., asthma).^{146 c g} Manufacturer recommends against use with other β-adrenergic bronchodilators.^{c f} (See Specific Drugs under Interactions.)

Current asthma management guidelines and most clinicians recommend anti-inflammatory therapy with an orally inhaled corticosteroid as first-line therapy for long-term control of persistent asthma, supplemented by intermittent, as-needed use of a short-acting, inhaled β₂-agonist.^{j o}

The National Asthma Education and Prevention Program (NAEPP) does not recommend nonselective β-adrenergic agonists, including metaproterenol,^{j k} for treatment of asthma because of the associated potential for excessive cardiac stimulation, particularly in high doses.^j

Bronchospasm in COPD

Symptomatic management of reversible bronchospasm in patients with COPD, including chronic bronchitis and emphysema.¹⁴⁶ Manufacturer recommends against use with other β-adrenergic bronchodilators.^{c f} (See Specific Drugs under Interactions.)

Alupent Dosage and Administration

General

• 
  

  Adjust dosage carefully according to individual requirements and response.^{146 c f g}

  
  

Administration

Administer orally^{146 f} or by oral inhalation via metered-dose inhaler or nebulizer.^{145 c}

Oral Inhalation

Metered-dose Inhaler

Oral inhalation aerosol delivers approximately 0.65 mg from mouthpiece per metered spray; 7-g or 14-g canister delivers 100 or 200 metered sprays, respectively.^c

Administer inhalation aerosol only with actuator provided by manufacturer.^d

Shake the inhaler well before use.^d

Avoid spraying aerosol into eyes.^d

Place the mouthpiece of the inhaler well into the mouth with lips closed around it.^d Exhale through nose as completely as possible.^d Inhale slowly and deeply through mouth.^d Actuate aerosol inhaler, hold breath for few seconds, withdraw mouthpiece, and exhale slowly.^d

Allow ≥2 minutes to elapse between inhalations from aerosol inhaler.^d

Clean inhalation aerosol inhaler by removing metal canister and running warm water through plastic mouthpiece.^d If soap used, rinse thoroughly with plain water.^d

Dosage

Available as metaproterenol sulfate; dosage expressed in terms of metaproterenol sulfate.^{145 c f}

Pediatric Patients

Bronchospasm in Asthma

Oral

Oral solution in children <6 years of age (limited experience): 1.3–2.6 mg/kg daily.^f

Oral solution in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.^f

Conventional tablets in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.¹⁴⁶

Oral solution in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.^f

Conventional tablets in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.¹⁴⁶

Oral Inhalation

Inhalation aerosol in children ≥12 years of age: 1.3 or 1.95 mg (2 or 3 inhalations).^c Usually no need to repeat dosing more often than every 3–4 hours.^{c d} If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.^{c d}

0.4 or 0.6% inhalation solution for nebulization in children ≥12 years of age: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.¹⁴⁵ Usually no need to repeat dosing more often than every 4 hours.^{145 g}

Adults

Bronchospasm in Asthma

Oral

Usually, 20 mg 3 or 4 times daily.^{146 f}

Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations).^c Usually no need to repeat dosing more often than every 3–4 hours.^d If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.^{c d}

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.¹⁴⁵ Usually no need to repeat dosing more often than every 4 hours.^{145 g}

Bronchospasm in COPD

Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations).^c Usually no need to repeat dosing more often than every 3–4 hours.^d If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.^{c d}

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily.¹⁴⁵ Usually no need to repeat dosing more often than every 4 hours.^{145 g}

Prescribing Limits

Pediatric Patients

Bronchospasm

Asthma

Oral Inhalation

Inhalation aerosol in children ≥12 years of age: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.^c

Adults

Bronchospasm in Asthma

Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.^d

Bronchospasm in COPD

Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.^d

Cautions for Alupent

Contraindications

Arrhythmias associated with tachycardia.^{145 146 c f}

Known hypersensitivity to metaproterenol or any ingredients in formulation.^{145 146 c f}

Warnings/Precautions

Warnings

Acute or Worsening Asthma

Oral inhalation therapy intended for acute symptomatic relief of bronchospasm.^{126 134 135}

Failure to respond to previously effective dosage of metaproterenol may indicate seriously worsening asthma.^{112 126 134 135} Contact a clinician if control of mild asthma deteriorates. Reevaluate asthma therapy and institute alternative regimens or therapy.^{112 126 134 135}

Excessive Doses

Fatalities have been associated with excessive use of inhaled sympathomimetic drugs; cardiac arrest occurred in several cases.^{145 c}

Paradoxical Bronchospasm

Possible life-threatening, acute paradoxical bronchospasm.^{b c} Occasionally occurs after repeated or excessive use of orally inhaled sympathomimetic amines.^{b g}

Discontinue therapy immediately if bronchoconstriction occurs and institute alternative therapy.^{b c}

Cardiovascular Effects

Possible clinically important cardiovascular effects, including cardiac arrhythmias (e.g., tachycardia), changes in BP, and related symptoms.^{146 b c f}

Cautious use recommended in patients with cardiovascular disorders (e.g., ischemic heart disease, CAD, cardiac arrhythmias, hypertension, CHF).^{145 146 c f}

Sensitivity Reactions

Rarely, immediate hypersensitivity reactions can occur.^{c f}

Possible acute bronchospasm.^{b c} (See Paradoxical Bronchospasm under Cautions.)

General Precautions

Nervous System Effects

In high doses, possible CNS stimulation.^b

Cautious use recommended in patients with seizure disorders and those with sensitivity to sympathomimetic amines.^{146 c}

Metabolic Effects

Possible hypokalemia, which may increase risk of adverse cardiovascular effects.^{k l m}

Cautious use recommended in patients with diabetes mellitus or hyperthyroidism.^{145 146 c f}

Specific Populations

Pregnancy

Category C.^{c f g}

Lactation

Not known whether metaproterenol is distributed into milk.^{c f g} With oral inhalation solution, use caution.^g Administer oral solution or inhalation aerosol to nursing women only if potential benefits to the woman outweigh the possible risk to infant.^{c f}

Pediatric Use

Safety and efficacy of oral inhalation aerosol or solution for nebulization not established in children <12 years of age.^{c g}

Safety and efficacy of oral tablets not established in children <6 years of age.^{146 b} Safety and efficacy of oral solution demonstrated in limited number of pediatric patients <6 years of age.^f

Common Adverse Effects

Inhalation aerosol: Nervousness, ^c headache,^c dizziness,^c palpitations,^c GI distress,^c tremor,^c throat irritation,^c nausea,^c vomiting,^c cough,^c asthma exacerbation.^c

Inhalation solution: Nervousness,^g tachycardia,^g tremor,^g nausea.^g

Oral tablets: Nervousness,¹⁴⁶ tachycardia,¹⁴⁶ tremor,¹⁴⁶ headache,¹⁴⁶ palpitations,¹⁴⁶ nausea,¹⁴⁶ GI distress,¹⁴⁶ dizziness,¹⁴⁶ asthma exacerbation, ¹⁴⁶ insomnia,¹⁴⁶ fatigue,¹⁴⁶ diarrhea,¹⁴⁶ bad taste,¹⁴⁶ vomiting,¹⁴⁶ drowsiness,¹⁴⁶ syncope,¹⁴⁶ hypertension,¹⁴⁶ pruritus,¹⁴⁶ appetite changes,¹⁴⁶ dry throat,¹⁴⁶ fever.¹⁴⁶

Oral solution: Tachycardia,^f nervousness,^f tremor,^f nausea,^f headache.^f

Interactions for Alupent

Specific Drugs

Drug	Interaction	Comments
Antidepressants, tricyclic	Increased effect on vascular system146 c f	Use caution146 c f
β-Adrenergic blocking agents	Antagonism of pulmonary effects, bronchospasmb n	If concomitant use necessary, use cardioselective β-adrenergic blocker without intrinsic sympathomimetic activity (e.g., metoprolol, atenolol, esmolol); use low dosages initially and titrate upward with cautionn
MAO inhibitors	Increased effect on vascular system 146 c f	Use caution146 c f
Methylxanthine derivatives	Pharmacokinetic interaction unlikelye Potential for increased cardiotoxic effects (e.g., arrhythmias)100 101 102 146 c g
Sympathomimetic agents	Additive effects and possible toxicityb c f	Concomitant use not recommendedc f Exercise extreme care and allow sufficient time to elapse prior to administration of another sympathomimetic agent146 c (See Duration under Pharmacokinetics)

Alupent Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability about 10%.^{f h}

Onset

Oral inhalation aerosol: ≤1 minute.^b

Oral: ≤15–30 minutes.^{146 b}

Oral inhalation solution: ≤5–30 minutes.^{b g}

Oral or oral inhalation: Peak effect ≤1 hour.^b

Duration

Oral: ≤4 hours for oral solution and ≥4 hours for tablets.^{146 f}

Oral inhalation aerosol: About 1–2.5 hours.^c

Oral inhalation solution: 4–6 hours.^g

Bronchodilating effect of metaproterenol persists for ≥1 hour longer than that of equipotent doses of isoproterenol.^b

Distribution

Extent

Not known if metaproterenol is distributed into milk.^c

Plasma Protein Binding

Approximately 10–15%.ⁱ

Elimination

Metabolism

Following oral administration, extensively metabolized in GI tract to sulfate conjugate.^{c i} Following oral inhalation, may be excreted as glucuronic acid conjugates.^{145 147}

Elimination Route

Oral: Excreted in urine (approximately 40%) mostly as sulfate metabolite.^{147 f i}

Half-life

Biphasic: Terminal half-life 1.5–6 hours.^{h i}

Stability

Storage

Oral

Solution and Tablets

Tight, light-resistant containers at 15–30°C.^{146 f} Protect from moisture.¹⁴⁶

Oral Inhalation

Oral inhalation aerosol: 15–25°C; avoid excessive humidity.^c

Oral inhalation solution: ≤25°C.¹⁴⁵ Discard solution if pinkish or darker than slightly yellow in color or if it contains a precipitate.^g

ActionsActions

• 
  

  Stimulates β-adrenergic receptors with little or no effect on α-adrenergic receptors.^b

  
  


• 
  

  Less selectivity for β₂-receptors than albuterol.^{b j} More selectivity for β₂-receptors than isoproterenol.^{c f i}

  
  


• 
  

  Stimulates the production of cyclic adenosine-3′,5′-monophosphate (cAMP),^{146 b f} which mediates bronchial smooth muscle relaxation and inhibition of release of proinflammatory mediators from mast cells in airways.^{146 b c f}

  
  


• 
  

  Decreases airway resistance.^{c f g}

  
  


• 
  

  In high doses, may cause CNS stimulation and some cardiostimulatory effects, which may result in tachycardia and hypertension.^b

  
  


• 
  

  Possible development of tolerance to bronchodilatory effects with prolonged therapy exceeding recommended dosages.^b

  
  

Advice to Patients

• 
  

  Importance of adherence to dosing schedules of metaproterenol and concomitant therapy, including not exceeding recommended dosage or frequency of use unless otherwise instructed by a clinician.^{b f}

  
  


• 
  

  Importance of using extreme care when considering administration of additional sympathomimetic agents.^f Importance of allowing a sufficient interval of time to elapse before administering another sympathomimetic agent.^f (See Specific Drugs under Interactions.)

  
  


• 
  

  Importance of contacting clinician if asthmatic symptoms worsen or adverse reactions or diminished response occurs with usual dosage;^{b f g} do not increase dose or frequency of administration.^{c f}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^c

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^c

  
  


• 
  

  Importance of advising patients of other important precautionary information.^{146 c f g} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Metaproterenol Sulfate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	10 mg/5 mL*	Metaproterenol Sulfate Syrup	Novex, Par, Silarx
	Tablets	10 mg*	Metaproterenol Sulfate Tablets	Par, Teva, Watson
		20 mg*	Metaproterenol Sulfate Tablets	Par, Teva, Watson
Oral Inhalation	Aerosol	0.65 mg/metered spray	Alupent (with chlorofluorohydrocarbon propellants)	Boehringer Ingelheim
	Solution, for nebulization	0.4%	Metaproterenol Sulfate Inhalation Solution	Dey
		0.6%	Metaproterenol Sulfate Inhalation Solution	Dey

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions September 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation solution prescribing information. Ridgefield, CT; 1995 July.

101. Joseph X, Whitehurst VE, Bloom S et al. Enhancement of cardiotoxic effects of β-adrenergic bronchodilators by aminophylline in experimental animals. Fundam Appl Toxicol. 1981; 1:443-7. [PubMed 6136445]

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122. O’Connor BJ, Aikman SL, Barnes PJ. Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma. N Engl J Med. 1992; 327:1204-8. [IDIS 304091] [PubMed 1357551]

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125. Reviewers’ comments (personal observations) on Salmeterol 12:12.

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127. Devoy MAB, Fuller RW, Palmer JBD. Are there any detrimental effects of the use of inhaled long-acting β₂-agonists in the treatment of asthma? Chest. 1995; 107:1116-24.

128. McFadden ER Jr. Perspectives in β₂-agonist therapy: vox clamantis in deserto vel lux in tenebris? J Allergy Clin Immunol. 1995; 95:641-51.

129. Crane J, Burgess C, Pearce N et al. Asthma deaths in New Zealand. BMJ. 1992; 304:1307. [IDIS 296806] [PubMed 1606438]

130. Crane J, Pearce N, Flatt A et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet. 1989; 1:917-22. [IDIS 254874] [PubMed 2565417]

131. Pearlman DS, Chervinsky P, LaForce C et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992; 327:1420-5.

132. D’Alonzo GE, Nathan RA, Henochowicz S et al. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. JAMA. 1994; 271:1412-6.

133. Drazen JM, Israel E, Boushey HA et al. Comparison of regularly scheduled with as- needed use of albuterol in mild asthma. N Engl J Med. 1996; 335:841-7.

134. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

135. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2002 Feb. NIH/NHLBI Publication No. 02-3659. Available from website. Accessed Sep. 26, 2002

136. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2001. Available at: . Accessed Sep. 26, 2002.

137. American Thoracic Society. ATS Statement: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(Suppl):S78-120.

138. Veterans’ Health Administration Department of Veteran Affairs. The pharmacologic management of chronic obstructive pulmonary disease. Washington, DC: Veterans’ Health Administration; 1999 June. Pharmacy Benefits Management No. 99-0012. Available from website. Accessed Sep. 30, 2002.

139. Veterans’ Health Administration, Department of Veterans’ Affairs. VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease: complete summary. Washington, DC: Veterans’ Health Administration; 1999 Aug.

140. Boehringer Ingelheim. Atrovent (ipratropium bromide) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Mar.

141. ATS/ERS Standards for the diagnosis and management of patients with COPD. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available from website. Accessed Dec. 8, 2004.

142. O’Donnell DE, Aaron S, Bourbeau J et al. State of the art compendium: Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease. Can Respir J. 2004; 11 (Suppl. B):7B-59B. [PubMed 15340581]

143. Celli BR, Macnee W. Standard for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23:932-46. [PubMed 15219010]

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145. Dey. Metaproterenol sulfate (0.4 and 0.6%) inhalation solution. Napa , CA; 1998 Apr.

146. Par Pharmaceuticals. Metaproterenol tablets prescribing information. Spring Valley, NY; 2000 Sep.

147. MacGregor TR, Nastasi L, Farina PR et al. Isolation and characterization of metaproterenol-3-O-sulfate: a conjugate of metaproterenol in human urine. Drug Metab Dispos. 1983; 160:568-73.

b. AHFS drug information 2007. McEvoy GK, ed. Metaproterenol. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1321-3.

c. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation aerosol prescribing information. Ridgefield, CT; 1999 Feb.

d. Boehringer Ingelheim Pharmaceuticals Inc. Alupent (metaproterenol sulfate) inhalation aerosol patient instructions. Ridgefield, CT; 1999 Feb.

e. Upton RA. Pharmacokinetic interactions between theophylline and other medication. Clin Pharmacokinet. 1991; 20:66-80. [PubMed 1674242]

f. Apotex Corporation. Metaproterenol sulfate oral solution prescribing information. Weston, FL; 2005 May.

g. Dey. Metaproterenol sulfate (0.4 and 0.6%) inhalation solution prescribing information. Napa , CA; 2006 Jan.

h. Kelly HW. New β₂-adrenergic agonist aerosols. Clin Pharm. 1985; 4:393-403. [PubMed 2864159]

i. Hatch F, McKellop K, Hansen G et al. Relative bioavailability of metaproterenol in humans utilizing a single-dose, stable isotope approach. J Pharm Sci. 1986; 75:886-90. [PubMed 3783458]

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k. Burgess CD, Windom HH, Pearce N et al. Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma. Am Rev Respir Dis. 1991; 143(2):444-6. [PubMed 1671326]

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Sirolimus Solution

Pronunciation: sir-OH-li-mus
Generic Name: Sirolimus
Brand Name: Rapamune

Sirolimus Solution decreases the action of the immune system. This may increase your risk of infection. It may also increase your risk of developing certain types of cancer (eg, lymphoma, skin cancer). Tell your doctor right away if you notice signs of infection (eg, persistent sore throat, chills, fever), any changes in the appearance or size of a mole, night sweats, unusual growths or lumps, or unusual tiredness or weakness.

Sirolimus Solution may increase the risk of severe side effects, including death, when used with certain other immunosuppressants in liver or lung transplant patients. Use of Sirolimus Solution in liver or lung transplant patients is not recommended.

Sirolimus Solution is used for:

Preventing organ rejection after a kidney transplant. It is used with other medicines. It may also be used for other conditions as determined by your doctor.

Sirolimus Solution is an immunosuppressant. It works by blocking the action of certain blood cells (eg, T lymphocytes) that can cause the body to reject the transplanted organ.

Do NOT use Sirolimus Solution if:

• you are allergic to any ingredient in Sirolimus Solution


• you have had a liver or lung transplant


• you are taking astemizole, certain azole antifungals (eg, itraconazole, ketoconazole, voriconazole), certain macrolide antibiotics (eg, clarithromycin, erythromycin), rifabutin, rifampin, tacrolimus, telithromycin, or terfenadine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Sirolimus Solution:

Some medical conditions may interact with Sirolimus Solution. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are able to become pregnant


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have liver problems, kidney problems, high cholesterol or triglycerides, low blood platelet levels, diabetes, or a history of lung or breathing problems


• if you are on dialysis, have recently received or are scheduled to receive a vaccine, or have a history of tuberculosis (TB) or have ever had a positive TB skin test


• if you have had multiple organ transplants, an organ retransplanted, or a previous transplant that was rejected


• if you or a family member has a history of skin cancer


• if you previously took cyclosporin and have recently stopped taking it

Some MEDICINES MAY INTERACT with Sirolimus Solution. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Angiotensin-converting enzyme (ACE) inhibitors (eg, lisinopril) because the risk of a serious side effect (angioedema) involving swelling of the mouth, face, lips, tongue, throat, and hands; trouble swallowing or breathing; and unexplained hoarseness may be increased


• Amiodarone, azole antifungals (eg, fluconazole, itraconazole, ketoconazole, voriconazole), bromocriptine, cimetidine, cisapride, cyclosporine, danazol, diltiazem, dronedarone, hepatitis C virus (HCV) protease inhibitors (eg, boceprevir), HIV protease inhibitors (eg, ritonavir), macrolide antibiotics (eg, clarithromycin, erythromycin), metoclopramide, mibefradil, nicardipine, streptogramins (eg, dalfopristin), telithromycin, troleandomycin, or verapamil because they may increase the risk of Sirolimus Solution's side effects, including kidney problems


• Medicines that may harm the kidney (eg, aminoglycosides [eg, gentamicin], amphotericin B, nonsteroidal anti-inflammatory drugs [NSAIDs] [eg, ibuprofen], vancomycin) because the risk of kidney side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the kidney


• Carbamazepine, hydantoins (eg, phenytoin), phenobarbital, rifamycins (eg, rifabutin, rifampin, rifapentine), or St. John's wort because they may decrease Sirolimus Solution's effectiveness


• Astemizole , calcineurin inhibitors (eg, tacrolimus), fibrates (eg, fenofibrate), HMG-CoA reductase inhibitors (eg, atorvastatin), mycophenolate, or terfenadine because the risk of their side effects may be increased by Sirolimus Solution

This may not be a complete list of all interactions that may occur. Ask your health care provider if Sirolimus Solution may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Sirolimus Solution:

Use Sirolimus Solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Sirolimus Solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Sirolimus Solution refilled.


• Take Sirolimus Solution by mouth. You may take it with or without food. However, you must take it the same way each time for it to work best. If you take Sirolimus Solution on an empty stomach, always take it on an empty stomach. If you take it with food, always take it with food.


• Use the dosing syringe that comes with Sirolimus Solution to measure your dose. Keep the bottle upright while you measure your dose. If bubbles form in the syringe, empty the syringe into the bottle and start over. Ask your pharmacist for help if you are unsure of how to measure your dose.


• Empty the measured medicine from the syringe into a glass or plastic container that has at least 2 oz (60 mL) of water or orange juice in it. Do not mix with any other liquid. Stir well and drink at once. Refill the container with at least 4 oz (120 mL) of water or orange juice, stir well, and drink at once.


• You may draw a dose into the syringe, cap the syringe, and keep the medicine in the syringe for up to 24 hours before using it. The syringe should be stored at room temperature, up to 77 degrees F (25 degrees C), or in the refrigerator. Once you have mixed the medicine in liquid, you must drink it right away.


• Throw away each syringe after 1 use.


• If you spill Sirolimus Solution on your skin, wash it off right away with soap and water. If you get Sirolimus Solution in your eyes, rinse at once with cool tap water.


• Sirolimus Solution may become hazy when refrigerated. If this occurs, allow it to stand at room temperature and shake gently until the haze disappears. This will not affect the effectiveness of Sirolimus Solution.


• If it is necessary to wipe the mouth of the bottle, use a dry cloth so that no water or other liquid enters the bottle.


• If you are also taking cyclosporine, take Sirolimus Solution 4 hours after your cyclosporine dose, unless your doctor tells you otherwise.


• Grapefruit and grapefruit juice may increase the risk of side effects from Sirolimus Solution. Do not eat grapefruit or drink grapefruit juice while you take Sirolimus Solution.


• Sirolimus Solution works best if it is taken at the same time each day. Continue to take Sirolimus Solution even if you feel well. Do not miss any doses.


• Do not stop taking Sirolimus Solution without first checking with your doctor.


• If you miss a dose of Sirolimus Solution, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Sirolimus Solution.

Important safety information:

• Do not change your dose of Sirolimus Solution without first checking with your doctor.


• Sirolimus Solution may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Some patients treated with Sirolimus Solution have developed severe and sometimes fatal infections, such as progressive multifocal leukoencephalopathy (PML) or severe kidney problems associated with BK virus infection. In kidney transplant patients, BK virus infection may cause loss of the transplanted kidney. Tell your doctor right away if you notice symptoms of PML (eg, confusion; disorientation; depression; changes in thinking, strength, or vision; one-sided weakness; trouble walking or talking; loss of balance or coordination) or kidney problems (eg, change in the amount of urine, difficult or painful urination, blood in the urine). Discuss any questions or concerns with your doctor.


• Sirolimus Solution may increase your risk of developing certain types of cancer (eg, lymphoma, skin cancer). Discuss any questions or concerns with your doctor.


• To decrease your risk of skin cancer, avoid using sunlamps or tanning booths. Limit your exposure to the sun. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Do not receive a live vaccine (eg, measles, mumps) while you are taking Sirolimus Solution. Talk with your doctor before you receive any vaccine.


• Sirolimus Solution may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


• Do not switch between the tablet and solution forms of Sirolimus Solution without first checking with your doctor. The same doses may not be equally effective.


• Tell your doctor or dentist that you take Sirolimus Solution before you receive any medical or dental care, emergency care, or surgery.


• If you may become pregnant, you must use an effective form of birth control before you start taking Sirolimus Solution. You will need to continue to use birth control while you take Sirolimus Solution and for 12 weeks after you stop taking it. If you have questions about effective birth control, talk with your doctor.


• Decreased sperm production has occurred in some men taking Sirolimus Solution. Normal sperm production has usually returned when Sirolimus Solution was stopped. Discuss any questions or concerns with your doctor.


• Patients who take Sirolimus Solution after an organ transplant may have an increased risk of developing high blood sugar or diabetes. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.


• Lab tests, including complete blood cell counts, kidney function, urine protein, blood cholesterol and triglyceride levels, and sirolimus blood levels, may be performed while you take Sirolimus Solution. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Sirolimus Solution should be used with extreme caution in CHILDREN younger than 13 years old; safety and effectiveness in these children have not been confirmed.


• Sirolimus Solution should be used with extreme caution in CHILDREN younger than 18 years old who are considered to be at high immunological risk; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Sirolimus Solution may cause harm to the fetus. Do not become pregnant while you are taking it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Sirolimus Solution while you are pregnant. It is not known if Sirolimus Solution is found in breast milk. Do not breast-feed while taking Sirolimus Solution.

Possible side effects of Sirolimus Solution:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Acne; constipation; diarrhea; headache; joint pain; nausea; stomach pain.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest or throat; swelling of the mouth, face, lips, or tongue; unusual hoarseness; wheezing); calf or leg pain, redness, tenderness, or swelling; chest pain; fainting; fast or irregular heartbeat; mental or mood changes; muscle pain, cramps, or tenderness; new or worsening breathing problems (eg, shortness of breath); new or worsening cough; night sweats; red, swollen, blistered, or peeling skin; severe or persistent headache or dizziness; skin growths or discoloration; swelling of the hands, ankles, feet, or stomach; swelling or soreness of the mouth or tongue; swollen glands or veins; symptoms of infection (eg, chills, fever, frequent or painful urination, sore throat, unusual vaginal discharge or odor); symptoms of kidney problems (eg, blood in the urine, change in the amount of urine, difficult or painful urination); symptoms of liver problems (eg, dark urine, loss of appetite, pale stools, yellowing of the skin or eyes); symptoms of PML (eg, changes in thinking, strength, or vision; confusion; depression; disorientation; loss of balance or coordination; one-sided weakness; trouble walking or talking); tremor; unusual bleeding or bruising; unusual lumps; unusual tiredness or weakness; unusual weight gain or loss; vision changes; wound healing problems.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Sirolimus side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Sirolimus Solution:

Store Sirolimus Solution in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do NOT freeze. If necessary, the bottle may be stored at room temperature, up to 77 degrees F (25 degrees C), for no more than 15 days. Store away from heat, moisture, and light. Do not store in the bathroom. Throw away any unused medicine after the bottle has been open for 1 month. Keep Sirolimus Solution out of the reach of children and away from pets.

General information:

• If you have any questions about Sirolimus Solution, please talk with your doctor, pharmacist, or other health care provider.


• Sirolimus Solution is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Sirolimus Solution. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Sirolimus resources

• Sirolimus Side Effects (in more detail)
• Sirolimus Use in Pregnancy & Breastfeeding
• Sirolimus Drug Interactions
• Sirolimus Support Group
• 0 Reviews for Sirolimus - Add your own review/rating

Compare Sirolimus with other medications

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