1. Name Of The Medicinal Product
Clarithromycin 500 mg, Powder for Concentrate for Solution for Infusion
2. Qualitative And Quantitative Composition
Each vial contains 500 mg clarithromycin (as lactobionate).
Each millilitre of final reconstituted/diluted solution for infusion contains 2 mg clarithromycin (as lactobionate).
For excipients, see 6.1
3. Pharmaceutical Form
Powder for Concentrate for Solution for Infusion.
White crystalline powder
4. Clinical Particulars
4.1 Therapeutic Indications
Clarithromycin 500 mg, powder for concentrate for solution for infusion is indicated when parenteral therapy is required for treatment of infections, caused by clarithromycin-susceptible organisms in the following conditions:
- Community acquired pneumonia
- Acute exacerbation of chronic bronchitis
- Acute bacterial sinusitis (adequately diagnosed)
- Bacterial pharyngitis and tonsillitis
- 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
Method of administration
For intravenous administration only.
Clarithromycin may be given for 2 to 5 days by intravenous infusion, however, patients should be switched to the oral therapy should longer term treatment be required.
Adults and adolescents: The recommended dose is 1.0 gram daily of Clarithromycin powder for concentrate for solution for infusion (appropriately diluted as described below), administered as two separate 500mg doses at 12 hourly intervals.
Children aged 12 or less: At present, there is insufficient data to recommend a dosage regimen for use in children.
Elderly: Same as for adults.
Renal Impairment:
Patients with severe renal impairment, with creatinine clearance less than 30ml/min, the dosage of clarithromycin should be reduced to one half of the normal recommended dose.
Recommended administration:
Clarithromycin 500 mg, powder for concentrate for solution for infusion should be administered into one of the larger proximal veins as an IV infusion over 60 minutes, using a solution concentration of about 2mg/ml. Clarithromycin should not be given as a bolus or an intramuscular injection.
4.3 Contraindications
Clarithromycin 500 mg, powder for concentrate for solution for infusion, must not be used in patients with known hypersensitivity to macrolide antibiotic drugs.
Concomitant use of clarithromycin and simvastatin should be avoided.
Clarithromycin and ergot derivatives should not be co-administered (see section 4.5).
Elevated levels of cisapride, pimozide and terfenadine levels have been reported in patients receiving either of these medicinal products and clarithromycin concomitantly. Simultaneous administration of Clarithromycin with any of these active substances is thus contraindicated. It may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsade de Pointes.
Similar effects have been observed with concomitant administration of astemizole and other macrolides.
4.4 Special Warnings And Precautions For Use
Clarithromycin is principally excreted by the liver and kidney. Caution should be exercised in administering this antibiotic to patients with impaired hepatic and renal function or those concomitantly receiving potentially hepatotoxic drugs.
Attention should be paid to the possibility of cross resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Super-infections, like an overgrowth of non-susceptible bacteria or fungi may result due to prolonged or repeated use of Clarithromycin. In such cases, the antibiotic should be discontinued and appropriate therapy instituted.
On concomitant use of clarithromycin and colchicine, post-marketing reports of colchicine toxicity have been reported, especially in the elderly, some of which occurred in patients with renal insufficiency. Reports of death also have been reported in some such patients (see Section 4.5).
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening. Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile.
“CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents”
Exacerbation of symptoms of myasthenia gravis has been reported in patients receiving clarithromycin therapy.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Effects of other medicinal products on clarithromycin
Clarithromycin is metabolised via enzyme CYP3A4. Therefore, strong inhibitors of this enzyme may inhibit clarithromycin metabolism, this results in increased plasma concentrations of clarithromycin.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine
Strong inducers of the cytochrome P450 metabolism system such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine may accelerate the metabolism of clarithromycin and thus lower the plasma levels of clarithromycin, while increasing those of 14-(R)-hydroxy-cvlarithromycin (14-OH-clarithromycin), a metabolite that is also microbiologically active. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
Fluconazole
Concomitant administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers led to increases in the mean steady-state minimum clarithromycin concentration (Cmin) and area under the curve (AUC) of 33% and 18% respectively. Steady state concentrations of the active metabolite 14-OH-clarithromycin were not significantly affected by concomitant administration of fluconazole. No clarithromycin dose adjustment is necessary.
It has been demonstrated that ritonavir (200 mg of ritonavir three times daily) is an inhibitor of clarithromycin (500 mg twice daily) metabolism, whereas an increase of Cmax, Cmin and AUC in concomitant administration with ritonavir are 31, 182 and 77%, respectively. Formation of the active metabolite 14->R@-hydroxyclarithromycin has been almost completely inhibited. In patients with normal renal function the dose of clarithromycin need not be decreased, however, clarithromycin daily dose must not exceed 1 g. A dose reduction should be considered in patients with renal impairment. In patients with creatinine clearance of 30-60 ml/min (0.5 – 1 ml/s) the dose of clarithromycin should be reduced by 50% and in patients with creatinine clearance of <30 ml/min (<0.5 ml/s) the dose should be reduced by 75%.
Although the plasma concentrations of clarithromycin and omeprazole may be increased when they are administered concurrently, no dose adjustment is necessary. Increased plasma concentrations of clarithromycin may also occur when it is coadministered with antacids or ranitidine.No adjustment to the dosage is necessary.
CYP3A4 inducers (such as rifampicine, phenytoin, carbamazepine, phenobarbital, products containing St. John Wort) may induce clarithromycin metabolism. This may result in sub-therapeutic levels of clarithromycin which decrease the product´s efficacy. If clarithromycin is clearly indicated, it may be necessary to increase the dose of clarithromycin, and closely monitor its efficacy and safety. Further monitoring of plasma levels of the CYP3A4 inducer may be necessary, because the levels may be increased due to CYP3A4 inhibition by clarithromycin (see also relevant Summary of Product Characteristics of the administered CYP3A4 inducer).
Concomitant administration of rifabutine and clarithromycin has resulted in increased rifabutine levels and decreased clarithromycin levels in serum, and in an increased risk of uveitis.
A 39% reduction in AUC for clarithromycin and a 34% increase in AUC for the active 14-OHhydroxy metabolite have been seen when clarithromycin was used concomitantly with the CYP3A4 inducer efavirenz.
Effects of clarithromycin on other medicinal products
Clarithromycin is an inhibitor of metabolising enzyme CYP3A4 and transport Pglycoprotein.
The inhibition level for various CYP3A4 substrates is very difficult to predict. Therefore, clarithromycin should not be used during treatment with other medicinal products which are CYP3A4 substrates, unless their plasma levels, therapeutic effects, or adverse effects of the CYP3A4 substrate can be closely monitored. Medicinal products which are CYP3A4 substrates and are given concomitantly with clarithromycin may require a dose reduction. Alternatively, treatment with these medicinal products may be interrupted during the treatment with clarithromycin.
Medicinal products which may prolong QT interval
Clarithromycin is considered to be an inhibitor of cisapride and terfenadine metabolism with a twofold up to three-fold increase of terfenadine plasma levels. The latter is associated with a QT interval prolongation and heart arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Similar symptoms have been reported in patients who were treated with pimozide in combination with clarithromycin. Concomitant administration of clarithromycin and terfenadine, cisapride, pimozide and astemizole is contraindicated (see section 4.3).
Torsades de pointes have been reported in patients who were concomitantly receiving clarithromycin and quinidine or disopyramid. Therefore, these combinations must be avoided, or quinidine or disopyramid plasma levels must be closely monitored. A dose adjustment may be necessary. If clarithromycin is given to patients who are treated with other products which may prolong QT interval, cautions should be exercised (see section 4.4).
Ergot vasoconstrictors (e.g. dihydroergotamin, ergotamin)
Post-marketing reports indicate that co-administration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischaemia of the extremities and other tissues including the central nervous system (see section 4.3).
HMG-CoA reductase inhibitors
Clarithromycin is an inhibitor of metabolism of some HMG-CoA reductase inhibitors, this results in an increase of plasma concentrations of these substances.
Rarely, rhabdomyolysis together with increased plasma concentrations have been reported in patients receiving clarithromycin and simvastatin or lovastatin. Clarithromycin may cause similar interactions with atorvastatin. If clarithromycin treatment is indicated in patients treated with simvastatin, lovastatin, or atorvastatin, those patients must be monitored for occurrence of signs of myopathy.
Tolterodine
The primary route of metabolism for tolterodine is via the 2D6 isoform of cytochrome P450 (CYP2D6). However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. A reduction in tolterodine dosage may be necessary in the presence of CYP3A inhibitors, such as clarithromycin in the CYP2D6 poor metabolizer population.
Benzodiazepines
In concomitant administration of midazolam with clarithromycin tablets (250 mg twice daily), AUC of midazolam has increased 2.7-fold and 7-fold following intravenous administration and following oral administration of midazolam, respectively. Concomitant administration of midazolam tablets and clarithromycin should be avoided. In intravenous concomitant administration of midazolam and clarithromycin, the patient should be closely monitored. A dose adjustment may be necessary. The same precautions should also be applied while using other benzodiazepines metabolised via CYP3A4, in particular triazolam as well as alprazolam. An interaction with clarithromycin is unlikely in benzodiazepines which are not metabolised via CYP3A4 (temazepam, nitrazepam, lorazepam).
Cyclosporin, tacrolimus and sirolimus
Concomitant administration of the oral form of clarithromycin with cyclosporin or tacrolimus results in more than a two-fold increase of Cmin plasma concentrations of cyclosporin and tacrolimus. Similar effects can also be expected with sirolimus.
Plasma levels of cyclosporin, tacrolimus or sirolimus should be thoroughly monitored when commencing treatment with clarithromycin in patients on any of the above mentioned immunosuppresants, and their doses should be decreased, if necessary.
Clarithromycin discontinuation in those patients also requires a thorough monitoring of cyclosporin, tacrolimus or sirolimus plasma levels to guide dose adjustment.
Medicinal products transported by P-glycoprotein
Clarithromycin is a potent inhibitor of the transport protein P-glycoprotein (Pgp).This could give rise to increased plasma concentrations of active substances which are transported by this transporter and may also increase distribution of such active substances to organs having Pgp as an distribution barrier e.g. CNS.
The plasma concentration of the digoxin may be increased when co-administered with clarithromycin. Monitoring of plasma levels of digoxin should be considered when co-treatment with clarithromycin is initiated or terminated since a dose adjustment may be warranted.
Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp).When clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical symptoms of colchicine toxicity
Theophylline
Clarithromycin administration to patients on theophylline is associated with an increase of theophylline serum concentration, and potential theophylline toxicity
Warfarin
The use of Clarithromycin in patients receiving warfarin may result in a potentiation of the effects of warfarin. Prothrombin time should be frequently monitored in these patients.
Zidovudine
Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV infected adults may result in decreased steady-state zidovudine concentrations. Since this interaction in adults is thought to be due to interference of clarithromycin with simultaneously administered oral zidovudine, this interaction should not be a problem when clarithromycin is administered intravenously. With oral clarithromycin, the interaction can be largely avoided by staggering the doses; see Summary of Product Characteristics for Clarithromycin tablets for further information. No similar reaction has been reported in children.
The use of clarithromycin in patients concurrently taking other drugs metabolized by the cytochrome p450 system (e.g. cilostazol, methylprednisolone, sildenafil, vinblastine ) may be associated with elevations in serum levels of these other medicinal products.
Clarithromycin has been shown not to interact with oral contraceptives.
Bi-directional drug interactions
Atazanavir
Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. Co-administration of clarithromycin (500 mg twice daily) with atazanavir (400 mg once daily) resulted in a 2-fold increase in exposure to clarithromycin and a 70% decrease in exposure to 14-OHclarithromycin, with a 28% increase in the AUC of atazanavir. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. For patients with moderate renal function (creatinine clearance 30 to 60 mL/min), the dose of clarithromycin should be decreased by 50%.
For patients with creatinine clearance <30 mL/min, the dose of clarithromycin should be decreased by 75% using an appropriate clarithromycin formulation. Doses of clarithromycin greater than 1000 mg per day should not be coadministered with protease inhibitors.
Itraconazole
Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, leading to a bidirectional drug interaction. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effect.
Saquinavir
Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. Concomitant administration of clarithromycin (500 mg bid) and saquinavir (soft gelatin capsules, 1200 mg tid) to 12 healthy volunteers resulted in steady-state AUC and Cmax values of saquinavir which were 177% and 187% higher than those seen with saquinavir alone. Clarithromycin AUC and Cmax values were approximately 40% higher than those seen with clarithromycin alone. No dose adjustment is required when the two drugs are coadministered for a limited time at the doses/formulations studied. Observations from drug interaction studies using the soft gelatin capsule formulation may not be representative of the effects seen using the saquinavir hard gelatin capsule. Observations from drug interaction studies performed with saquinavir alone may not be representative of the effects seen with the combination therapy of saquinavir and ritonavir, therefore when this combination therapy is coadministered with clarithromycin consideration should be given to the potential effects of ritonavir on clarithromycin (see Section 4.5-Ritonavir).
Verapamil
Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients taking clarithromycin and verapamil concomitantly.
4.6 Pregnancy And Lactation
The safety of Clarithromycin during pregnancy and breast-feeding of infants has not been established. Therefore clarithromycin should not be used during pregnancy or lactation unless the benefit outweighs the risk.
Data from animal studies have shown reproductive toxicity (see section 5.3).Clarithromycin and its active metabolite are excreted in breast milk of lactating animals and in human breast milk.
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable Effects
In this section undesirable effects are defined as follows:
Very common (>1/10)
Common (>1/100, <1/10)
Uncommon (>1/1,000, <1/100)
Rare (>1/10,000, <1/1,000)
Very rare (<1/10,000), including isolated reports
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4.9 Overdose
No incidences of overdosage after IV administration of clarithromycin have been experienced as yet. However, reports indicate that the ingestion of large amounts of clarithromycin orally can be expected to produce gastro-intestinal symptoms.
Symptoms of overdose may largely correspond to the profile of adverse reactions, that could be treated by gastric lavage and supportive measures.
As with other macrolides, clarithromycin serum levels cannot be reduced by haemodialysis or peritoneal dialysis.
One patient who had a history of bipolar disorder ingested 8 grams of clarithromycin and showed altered mental status, paranoid behaviour, hypokalaemia and hypoxaemia.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: macrolides
ATC code: J01FA09
Mode of action
The mechanism of action of clarithromycin is based on the inhibition of the protein biosynthesis by its binding to the 50S subunit of the bacterial ribosome.
The 14(R)-hydroxy metabolite of clarithromycin, a product of the metabolisation of the parent substance which is found in humans, also has an antibacterial effect. The MICs of this metabolite are equal or twofold higher than the MICs of the parent compound except for H. influenzae where the 14- hydroxy metabolite is two-fold more active than the parent compound.
PK/PD Relationship
The most important pharmacodynamic parameters for predicting macrolide activity are not conclusively established. The time above MIC (T/MIC) may correlate best with efficacy for clarithromycin, however since clarithromycin concentrations achieved in respiratory tissues and epithelial lining fluids exceed those in plasma, using parameters based on plasma concentrations may fail to predict accurately the response for respiratory tract infections.
Mechanisms of resistance
Resistance to clarithromycin can be based on the following mechanisms:
• Target site modification: (conferred by the ermB gene) As a result of the methylation of 23S rRNS, the affinity for the ribosomal binding sites is reduced, leading to high- level macrolide resistance to macrolides (M) and cross reference to lincosamides (L) and Group B streptograms (SB) (so called MLSB phenotype);
• Active drug efflux: Resistance can be caused as a result of an increase in the number of active efflux pumps in the cytoplasmic membrane(so-called M phenotype); active drug efflux among pneumococci is mediated by a membrane efflux pump encoded by the mefA gene. This mechanism results in low to mid-level resistance.
• The enzymatic inactivation of macrolides is only of subordinate clinical importance.
EUCAST Breakpoints: Macrolides, lincosamides, streptogramins - EUCAST clinical MIC breakpoints 200 8-06-19 (v 1.2 )
A. Non-species related breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species not mentioned in the table or footnotes However, pharmacodynamic data for calculation of macrolide, lincosamines and streptogramins non-species related breakpoints are not robust, hence IE.
B. Erythromycin can be used to determine the susceptibility of the listed bacteria to the other macrolides (azithromycin, clarithromycin and roxithromycin). Macrolides administered intravenously are active against Legionella pneumophila (erythromycin MIC
C. Clarithromycin is used for the eradication of H. pylori (MIC
D. The correlation between H. influenzae macrolide MICs and clinical outcome is weak. Therefore, breakpoints for macrolides and related antibiotics were set to categorise wild type H. influenzae as intermediate.
Susceptibility:
The prevalence of acquired 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 advisce should be sought when the local prevalence of resistance increased is such that the utility of the agent in at least in some types of infections is questionable.
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° No actual data were available when the tables were published. Sensitivity is assumed in the primary literature, reference works and treatment recommendations.
$ The natural sensitivity of most isolates lies in the intermediate range.
+ The rate of resistance is above 50% in at least one region.
1 Rate of resistance in some studies
5.2 Pharmacokinetic Properties
The pharmacokinetics of clarithromycin and the 14-hydroxy metabolite are non-linear due to saturation of hepatic metabolism at high doses; steady state is achieved by day 3 of IV dosing.
Distribution
Clarithromycin penetrates rapidly into various body tissues and fluids. In adults the volume of distribution ranges from 200 to 400 litres. Tissue concentrations in lung and tonsils have been found to be several times higher than plasma levels.
Clarithromycin is 80% bound to plasma proteins at therapeutic levels.
Biotransformation and Elimination
Clarithromycin is metabolised in the liver by the cytochrome P-450 enzyme system quickly and to a large extent. The microbiologically active metabolite 14-hydroxyclarithromycin is formed by first pass metabolism as indicated by lower bioavailability of the metabolite following IV administration.
Following a single 500mg IV dose over 60 minutes, about 33% clarithromycin and 11% 14-hydroxyclarithromycin is excreted in the urine at 24 hours.
In patients with renal impairment an increase of clarithromycin plasma levels and its active metabolite has been observed.
5.3 Preclinical Safety Data
In acute toxicity studies in mouse and rat, the median lethal dose was greater than the highest feasible dose for administration (5g/kg).
In repeated dose studies, toxicity was related to dose, duration of treatment and species. Dogs were more sensitive than primates or rats. The major clinical signs at toxic doses included emesis, weakness, reduced food consumption and weight gain, salivation, dehydration and hyperactivity. In all species the liver was the primary target organ at toxic doses. Hepatotoxicity was detectable by early elevations of liver function tests. Discontinuation of the drug generally resulted in a return to or toward normal results. Other tissues less commonly affected included the stomach, thymus and other lymphoid tissues and the kidneys.
At near therapeutic doses, conjunctival injection and lacrimation occurred only in dogs. At a massive dose of 400mg/kg/day, some dogs and monkeys developed corneal opacities and/or oedema.
Fertility and reproduction studies in rats have shown no adverse effects. Teratogenicity studies in rats (Wistar (p.o.) and Sprague-Dawley (p.o. and i.v.)), New Zealand White rabbits and cynomolgous monkeys failed to demonstrate any teratogenicity from clarithromycin. However, a further similar study in Sprague-Dawley rats indicated a low (6%) incidence of cardiovascular abnormalities which appeared to be due to spontaneous expression of genetic changes. Two mouse studies revealed a variable incidence (3-30%) of cleft palate and in monkeys embryonic loss was seen but only at dose levels which were clearly toxic to the mothers.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactobionic acid.
6.2 Incompatibilities
None known.
However, Clarithromycin 500 mg, powder for concentrate for solution for infusion, should only be diluted with the diluents recommended.
6.3 Shelf Life
Unopened vials: 4 years
After reconstitution in 10 ml water for injections:
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 24 hours at 5°C. From a microbiological point of view, the product should be diluted immediately. If not diluted immediately in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C.
After dilution to 250 ml in an appropriate diluent:
Chemical and physical in-use stability has been demonstrated for 6 hours at 25°C and for 24 hours at 5°C.
From a microbiological point of view, the solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C.
6.4 Special Precautions For Storage
Do not store above 30° C.
Store in the original container in order to protect from light.
For storage conditions of the reconstituted/diluted medicinal product, see section 6.3.
6.5 Nature And Contents Of Container
26 ml, type II clear glass vial of European Pharmacopoeia quality, sealed with a type I bromobutyl stopper of European Pharmacopoeia quality and an aluminium flip-off cap.
Vials are packed in units of 1, 4 and 6. Pack size 500mg.
Not all pack sizes may be marketed
6.6 Special Precautions For Disposal And Other Handling
Clarithromycin 500 mg, powder for concentrate for solution for infusion should be administered into one of the larger proximal veins as an IV infusion over 60 minutes, using a solution concentration of about 2mg/ml. Clarithromycin should not be given as a bolus or by intramuscular injection.
For single use only.
A. Preparation of the vial solution
Inject 10 ml of water for injections into a vial containing the product. Shake until the vial contents have dissolved. Use only water for injections for the dissolution. Other solvents may result in the formation of a precipitate. Do not use solutions of inorganic salts or solutions containing preservatives.
1 ml of the vial solution prepared in this way contains 50 mg clarithromycin lactobionate.
For storage conditions for the reconstituted medicinal product see Section 6.3
B. Preparation of infusion solution
Make up 10ml of the vial solution prepared in step A (containing 500 mg clarithromycin lactobionate) to 250 ml using one of the following solutions: 0.9% Sodium Chloride, 5% Dextrose, 5% Dextrose in 0.3% sodium chloride, 5% Dextrose in 0.45% sodium chloride, 5% Dextrose in Ringer's lactate solution and Ringer's lactate solution.
1ml of the infusion solution prepared in this way contains 2mg clarithromycin lactobionate.
For storage conditions for the diluted medicinal product see Section 6.3
IMPORTANT: BOTH DILUENT STEPS (A and B) SHOULD BE COMPLETED BEFORE USE.
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
Goldshield Pharmaceuticals Limited,
NLA Tower, 12-16 Addiscombe Road,
Croydon, Surrey,
CR0 0XT,
United Kingdom.
8. Marketing Authorisation Number(S)
PL 12762/0404
9. Date Of First Authorisation/Renewal Of The Authorisation
28/06/2010
10. Date Of Revision Of The Text
05/2010
11 DOSIMETRY
IF APPLICABLE
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
IF APPLICABLE
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