Throza Tablets

Composition:

• Throza 250mg: Each film coated tablet contains Azithromycin dihydrate B.P equivalent to Azithromycin  250mg.
• Throza 500mg: Each film coated tablet contains Azithromycin dihydrate B.P equivalent to Azithromycin  500mg.

Clinical pharmacology:

• Throza tablets contain the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for oral administration.  Macrolide antibiotics are bacteriostatic agents that inhibit protein synthesis by binding reversibly to 50s ribosomal subunits of sensitive micro – organisms.
• Azithromycin is sequestered in leukocytes and therefore available at the site of infection in higher concentrations than serum levels. Although dosed for five days, azithromycin maintains therapeutic serum levels six days after discontinuing the drug.
• Azithromycin has been released for use in paediatric respiratory illnesses at a dosage of 10 mg/kg as a single dose on day one, followed by 5 mg/kg daily for four days (given as a single daily dose). The maximum paediatric daily dose is 500 mg on day one and 250 mg on days two through five. Azithromycin can be safely given down to six months of age. Studies have shown azithromycin to be as effective as amoxicillin/clavulanate in treating acute otitis media.

Antibacterial activity:

Azithromycin is generally less active than erythromycin against gram-positive organisms and slightly more active than either erythromycin or clarithromycin against H. influenzae and Campylobacter spp. Azithromycin is very active against M. catarrhalis, P. multocida, Chlamydia spp., M. pneumoniae, L. pneumophila, B. burgdorferi, Fusobacterium spp., N. gonorrhoeae.

Pharmacokinetics:

Following oral administration, Azithromycin is widely distributed throughout the body; bioavailability is approximately 37%. No significant decrease in bioavailability is observed when administered with a meal. Peak plasma levels are reached in 2-3 hours. Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days.

Kinetic studies of variable times ranging from hours to days after oral administration have shown markedly higher Azithromycin levels in tissue than in plasma (up to 50 times the maximum observed concentration in plasma) indicating that the drug is highly tissue bound. Concentrations in target tissues such as lung, tonsil and prostrate exceed the MIC90 for likely pathogens after a single dose of 500mg.

The amount of unchanged Azithromycin dose excreted in urine is 6% after oral administration. Azithromycin is primarily excreted through the liver.

Indications:

Adults:

Azithromycin tablets are indicated for mild to moderate infections caused by susceptible organisms: in lower respiratory tract infections including bronchitis due to Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae or Staphylococcus aureus and pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae ; in uncomplicated skin and soft tissue infections ; sinusitis due to Haemophilus influenzae, Streptococcus pneumoniae  or Staphylococcus aureus ; and as an alternative to first line therapy of pharyngitis/tonsillitis.

In sexually transmitted diseases in men and women, Azithromycin tablets are indicated in the treatment of uncomplicated genital infections due to Chlamydia trachomatis and /or non-multiresistant Neisseria gonorrhea. It is also indicated in the treatment of chancroid due to Haemophilus ducreyi.

Children:

Azithromycin tablets are indicated for pharyngitis/tonsillitis and otitis media caused by susceptible organisms in children over 45 kg.

Contraindications:

• Azithromycin is contraindicated in patients with a known hypersensitivity to Azithromycin, Erythromycin or any of the  macrolide antibiotics.
• Because of the theoretical possibility of ergotism, Azithromycin and ergot derivatives should not be co-administered.
• As the liver is the principal route of excretion of Azithromycin, it should not be prescribed in patients with hepatic disease.

Cautions:

• Rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal) have been reported. Some of these reactions with Azithromycin have resulted in recurrent symptoms and require a longer period of observation and treatment.
• Pseudomembranous colitis has been reported and may range in severity from mild to life-threatening. Therefore it is important to consider this diagnosis in patients with diarrhoea subsequent to administration of Azithromycin tablets.
• Observations for signs of superinfection with non-susceptible organisms, including fungi, are recommended.

Interactions:

• In patients receiving Azithromycin tablets and antacids, Azithromycin tablets should be taken at least one hour or two hours after the antacid.
• Some of the related macrolide antibiotics interfere with the metabolism of cyclosporin. In the absence of pharmacokinetic studies and clinical data investigating a possible interaction, caution should be exercised before co-administration of these two drugs. If co-administration is necessary, cyclosporin levels should be monitored and dose adjusted accordingly.
• Some of the macrolides have been reported to impair the metabolism of Digoxin (in the gut) in some patients. Hence in patients receiving concomitant Azithromycin and Digoxin, the possibility of raised Digoxin levels should be borne in mind.
• Azithromycin and Warfarin may be co-administered, but monitoring of the prothrombin time should be continued as routinely performed.
• A possible interaction between Terfenadine and Azithromycin however less frequent, cannot be excluded.

Pregnancy and lactation:

There is no enough data to establish safety and efficacy of Azithromycin in pregnancy and lactation. Use should only be on advice of your physician.

Dosage & administration:

Azithromycin tablets should be swallowed whole as a single daily dose with or without food.

Adults:

• For all indications other than sexually transmitted diseases, the total dose is 1.5 gm which should be given as 500mg once daily for 3days.
• For sexually transmitted diseases caused by Chlamydia trachomatis or Haemophilus ducreyi and uncomplicated genital infections caused by non-multiresistant N.gonorrhoea, the dose is 1 gm given as a single oral dose.

Use in the elderly:

• Normal adult dosage is recommended.

Use in children:

• Children over 45 kg- dose as per adults.

Side-effects:

Nausea, vomiting, abdominal discomfort, diarrhoea, urticaria,, rashes & other allergic reactions; reversible hearing loss reported after large doses; cholestatic jaundice, cardiac effects ( chest pain & arrhythmias), myasthenia-like syndrome, stevens-johnson syndrome, anorexia, dyspepsia, constipation, dizziness, headache, drowsiness, photosensitivity, hepatitis, interstitial nephritis, acute renal failure, asthenia, convulsions, hepatic necrosis, hepatic failure & taste disturbances.

Overdose:

• There is no data on overdose with Azithromycin. Typical symptoms of overdose  with macrolide antibiotics include  loss of hearing, severe nausea, vomiting and diarrhoea.
• Gastric lavage and general supportive measures are indicated.

Presentation:

• Throza 250mg: Blister pack of  6`s in unit boxes; 30’s, 50’s and 100’s in plastic securitainer container.
• Throza 500mg: Blister pack of  3`s in unit boxes.

Storage:.

• Do not store above 30⁰C.  Store in a dry place. Protect from direct sunlight. Keep out of reach of children.
• Legal category:
• Prescription only medicine (P.O.M).