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Drug Details

Alimta 100mg/500mg powder for concentrate

• Drug Class Description
  Pharmacotherapeutic group: Folic acid analogues. ATC code: L01BA04. ALIMTA (pemetrexed) is a multi-targeted anti-cancer antifolate agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication.
• Presentation
  Powder for concentrate for solution for infusion. White to either light yellow or green-yellow lyophilised powder
• Description
  ALIMTA* 100mg and 500mg powder for concentrate for solution for infusion. Each 100mg vial contains 100mg of pemetrexed (as pemetrexed disodium). Excipients: Each vial contains approximately 11mg sodium. Each 500mg vial contains 500mg of pemetrexed (as pemetrexed disodium). Excipients: Each vial contains approximately 54mg sodium. After reconstitution, each vial contains 25mg/ml of pemetrexed.
• Indications
  Azithromycin powder for oral suspension is indicated for the treatment of the following infections, when caused by microorganisms sensitive to azithromycin: - upper respiratory tract infections: sinusitis, pharyngitis, tonsillitis - acute otitis media - lower respiratory tract infections: acute bronchitis and mild to moderately severe community acquired pneumonia - skin and soft tissue infections - uncomplicated Chlamydia trachomatis urethritis and cervicitis Considerations should be given to official guidance on the appropriate use of antibacterial agents. Azithromycin is not the first choice for the empiric treatment of infections in areas where the prevalence of resistant isolates is 10% or more
• Adult Dosage
  

  See summary of product characteristics.

• Contra Indications
  

  Hypersensitivity to azithromycin, to other macrolide antibiotics, or to any of the excipients.

• Special Precautions
  

  As with erythromycin and other macrolide antibiotics serious allergic reactions are rarely reported, these include angio-oedema and anaphylaxis (rarely fatal). Some of these reactions have resulted in recurrence of symptoms whereby a longer period of observation and treatment was necessary.

  As is true of all antibiotics, it is advisable to be alert to signs of superinfection by non-sensitive micro-organisms including fungi.

  Pseudomembranous colitis has been reported with the use of macrolide antibiotics. This diagnosis should also be considered in patients who get diarrhoea after starting treatment with azithromycin.

  There is no experience of the safety and effectiveness of long-term use of azithromycin in the above-mentioned indications. In the event of quickly recurring infections, just as is the case with other antibiotics, treatment with another antibacterial drug should be considered.

  Due to the theoretical possibility of ergotism, azithromycin and ergotamine derivatives should not be given at the same time.

  Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarisation. Therefore azithromycin should not be used:

  - in patients with congenital or documented acquired QT prolongation.

  - with other active substances that prolong QT interval such as antiarrhythmics of classes IA and III, cisapride and terfenadine.

  - in patients with electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia

  - in patients with clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

   

  The following should be considered before prescribing azithromycin:

  Azithromycin powder for oral suspension is not suitable for treatment of severe infections where a high concentration of the antibiotic in the blood is rapidly needed.

  In areas with a high incidence of erythromycin A resistance, it is especially important to take into consideration the evolution of the pattern of susceptibility to azithromycin and other antibiotics.

  As for other macrolides, high resistance rates of Streptococcus pneumoniae (> 30 %) have been reported for azithromycin in some European countries. This should be taken into account when treating infections caused by Streptococcus pneumoniae.

   

  Pharyngitis/ tonsilitis

  Azithromycin is not the substance of first choice for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes. For this and for the prophylaxis of acute rheumatic fever penicillin is the treatment of first choice.

   

  Sinusitis

  Often, azithromycin is not the substance of first choice for the treatment of sinusitis.

   

  Acute otitis media

  Often, azithromycin is not the substance of first choice for the treatment of acute otitis media.

   

  Infected burn wounds

  Azithromycin is not indicated for the treatment of infected burn wounds.

   

  Sexually transmitted disease

  In case of sexually transmitted diseases a concomitant infection by T. palladium should be excluded.

  Azithromycin should be used with caution in patients with neurological or psychiatric disorders.

  Use in renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10–80 ml/min). Caution is advised in patients with severe renal impairment (GFR < 10 ml/min) as systemic exposure may be increased.

  Use in hepatic impairment: Since azithromycin is metabolised in the liver and excreted in the bile, the medicinal product should not be given to patients suffering from severe liver disease. No studies have been conducted regarding the treatment of such patients with azithromycin. When severe liver impairment occurs, the treatment with azithromycin should be ceased.

  Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine since it contains sucrose.

• Interactions
  

  Theophylline

  Pharmacokinetic research has shown no interaction between azithromycin and theophylline on co-administration to healthy volunteers. As interactions of other macrolides with theophylline have been reported, alertness to signs that indicate a rise in theophylline levels is advised.

  Oral coumarin-type anticoagulants

  In pharmacokinetic research in healthy volunteers, azithromycin did not alter the anticoagulant effect of one dose of 15 mg warfarin. There are reports of enhanced anticoagulation in co-administration of azithromycin with oral coumarin-type anticoagulants. Although a causal connection has not been established, attention should be paid to the frequency of measurement of the prothrombin time.

  Carbamazepine

  In a pharmacokinetic interaction study in healthy volunteers, no significant effect was seen on the pharmacokinetics of carbamazepine or the active metabolite of carbamazepine.

  Ergotamine derivatives

  In patients who are being treated with ergotamine derivatives, ergotism may be induced by co-administration of some macrolide antibiotics. There are no known data on a possible interaction between ergotamine derivatives and azithromycin. As there is a theoretical possibility of ergotism, azithromycin and ergotamine derivatives should not be combined.

  Ciclosporin

  On the basis of limited pharmacokinetic data on interaction between azithromycin and ciclosporin in healthy volunteers, caution should be exercised in concurrent administration of these medicinal products. If concurrent administration is necessary, the ciclosporin levels must be checked and if necessary the ciclosporin dosage adjusted.

  Digoxin

  It is known that some macrolide antibiotics limit the metabolism of digoxin in the bowel. In patients who are treated concurrently with azithromycin and digoxin, account should be taken of potentially raised digoxin levels and these levels must be monitored.

  Antacids

  In a pharmacokinetic study into the effect of concurrent administration of antacids and azithromycin, no effect was seen on the total biological availability, although peak serum levels were reduced by 30%. Azithromycin must be taken at least 1 hour before or 2 hours after antacids.

  Cimetidine

  A single dose of cimetidine administered 2 hours before azithromycin had no effect on the pharmacokinetics of azithromycin.

   

  Methylprednisolone

  In a pharmacokinetic interaction study in healthy volunteers, no significant effect was seen on the pharmacokinetics of methylprednisolone.

  Zidovudine

  Single doses of 1000 mg azithromycin and multiple doses of 600 mg or 1200 mg Azithromycin had no effect on the plasma pharmacokinetics or the renal excretion of zidovudine or its glucuronide metabolite. However, on administration of azithromycin the concentration of phosphorylated zidovudine, the clinically active metabolite, increased in the peripheral mononuclear blood cells. The clinical significance of this finding is still unclear, but may possibly be an advantage for patients.

  Terfenadine

  Azithromycin has no effect on the pharmacokinetics of terfenadine, given every 12 hours at the recommended dosage of 60 mg. Addition of azithromycin did not result in a significant change of cardiac repolarization (QT interval), measured at a steady state dosage of terfenadine.

   

  Cisapride

  Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsades de pointes.

   

  Didanosine

  On comparison with a placebo in 6 test subjects, daily doses of 1200 mg azithromycin with didanosine appeared to have no effect on the pharmacokinetics of didanosine.

   

  Rifabutin

  Concurrent administration of azithromycin and rifabutin had no effect on the serum concentration of either medicinal product. Neutropenia was seen in patients who were given simultaneous treatment with azithromycin and rifabutin. In spite of the fact that neutropenia has been associated with the use of rifabutin, no causal connection with the combination with Azithromycin could be established.

   

  Astemizole, triazolam, midazolam, alfentanil

  There are no known data on interactions with astemizole, triazolam, midazolam or alfentanil. Caution is advised in the co-administration of these medicines with azithromycin because of the known enhancing effect of these medicines when used concurrently with the macrolide antibiotic erythromycin.

   

  Indinavir

  Coadministration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.

   

  Nelfinavir

  Concomitant administration of 1200 mg azithromycin and steady state nelfinavir (750 mg 3 times daily) resulted in on average 16% decrease of nelfinavir AUC, an increase of azithromycin AUC and Cmax with 113% and 136% respectively. No dose adjustment is necessary but patients should be monitored for known side effects of azithromycin.

   

• Adverse Drug Reactions
  

  See summary of product characteristics.