Composition and excipients:

Each Bactimycin F.C.tablet contains:

• active ingredients: Clarithromycin 250,500 mg.
• inactive ingredients:

Core: Croscarmellose sodium, Magnesium stearate, Microcrystalline cellulose, Povidone, Corn starch, Silicon dioxide,  Stearic acid, and Talc

Film:Hydroxypropyl methylcellulose, Sorbitan monooleate, and titanium dioxide.

Each 5ml of Bactimycin oral suspension contains:

• activity ingredients: Bactimycin oral suspension contains clarithromycin 125, 250 mg..
• inactive ingredients: Sucrose, Methylcellulose, Sodium benzoate, Xanthan gum, and flavor.

Pharmacological properties:

Clarithromycin is a semi-synthetic macrolide antibiotic. Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible microorganisms resulting in inhibition of protein synthesis.

Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative microorganisms as well as most Mycobacterium avium complex (MAC) microorganisms. Clarithromycin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections:

Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, Mycobacterium avium complex (MAC) consisting of:Mycobacterium avium and Mycobacterium intracellulare, Helicobacter pylori.

Notes:

– Beta-lactamase production should have no effect on clarithromycin activity.

– Most strains of methicillin-resistant and oxacillin-resistant staphylococci are  resistant to clarithromycin.

Pharmacokinetics:

After oral administration, Clarithromycin is rapidly absorbed from the gastrointestinal tract and may be given without regard to food.

Adults:

After oral dosage 250 mg ( q 12h ),  The absolute bioavailabilityof clarithromycin is approximately 50%. Peak plasma concentrations are attained within 2 to 3 hours. Steady-state peak plasma clarithromycin concentrations are attained within 3 days and are approximately 1 to 2 µg/ml. The elimination half-life of clarithromycin is about 3 to 4 hours.

the principal metabolite, 14-OH clarithromycin, attains a peak steady-state concentration of about 0.6 µg/ml and has an elimination half-life of 5 to 6 hours.

After oral dosage 500 mg ( q 8h –  12h ), Peak plasma concentrations are attained within 2 to 3 hours. Steady-state peak plasma clarithromycin concentrations are attained within 3 days and are approximately 3 to 4 µg/ml. The elimination half-life of clarithromycin is about 5 to 7 hours. the principal metabolite, 14-OH clarithromycin, attains a peak steady-state concentration of about 1 µg/ml and has an elimination half-life of 7 to 9 hours.

Children: In children requiring antibiotic therapy, administration of 7.5 mg/kg q12h doses of clarithromycin as the suspension generally resulted in steady-state peak plasma concentrations of 3 to 7 µg/ml for clarithromycin and 1 to 2 µg/ml for 14-OH clarithromycin. In HIV-infected children taking 15 mg/kg every 12 hours, steady-state clarithromycin peak concentrations generally ranged from 6 to 15 µg/ml.

Distribution: Clarithromycin and the 14-OH clarithromycin metabolite distribute readily into body tissues and fluids like lungs and tonsils. Tissue concentrations are higher than serum concentrations. Clarithromycin penetrates into the middle ear fluid of children with secretory otitis media.There are no data available on cerebrospinal fluid penetration.

Metabolism: Clarithromycin is metabolized by p-450 and results in antimicrobiological metabolite ( 14-OH clarithromycin).

Elimination: After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500-mg tablet every 12 hours, the urinary excretion of clarithromycin is approximately 30%. In comparision, after an oral dose of 250 mg (125 mg/5 ml) suspension every 12 hours, approximately 40% is excreted in urine as clarithromycin. The major metabolite found in urine is 14-OH clarithromycin, which accounts for an additional 10% to 15% of the dose with either a 250-mg or a 500-mg tablet administered every 12 hours. The renal clearance of clarithromycin is, however, relatively independent of the dose size and approximates the normal glomerular filtration rate.

– The pharmacokinetics of clarithromycin is also altered in subjects with impaired renal function.

Indications:

Adults:

– Pharyngitis/Tonsillitis due to Streptococcus pyogenes.

Note: The usual drug of choice in the treatment and prevention of streptococcal infections and the prophylaxis of rheumatic fever is penicillin administered by either the intramuscular or the oral route. Clarithromycin is generally effective in the eradication of S. pyogenes from the nasopharynx; however, data establishing the efficacy of clarithromycin in the subsequent prevention of rheumatic fever are not available at present.

– Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

– Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

– Community-Acquired Pneumonia due to Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydia pneumoniae.

– Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes. Abscesses usually require surgical drainage.

– Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare.

– Bactimycin tablets in combination with amoxicillin and lansoprazole or omeprazole , as triple therapy, are indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori or in combination with omeprazole or ranitidine are also indicated for the treatment of patients with an active duodenal ulcer associated with H. pylori infection.

Children:

– Pharyngitis/Tonsillitis due to Streptococcus pyogenes.

– Community-Acquired Pneumonia due to Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydia pneumoniae.

– Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

– Acute otitis media due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.

– Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes (Abscesses usually require surgical drainage.)

– Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare.

–Bactimycin ( Tablets and suspension) is indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.

Contraindications:

Bactimycin is contraindicated in patients with a known hypersensitivity to Clarithromycin, erythromycin, or any of the macrolide antibiotics.

Concomitant administration of Bactimycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated.

Warnings and precautions:

– Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and may range in severity from mild to life threatening. it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

– Clarithromycin is principally excreted via the liver and kidney. Clarithromycin may be administered without dosage adjustment to patients with hepatic impairment and normal renal function. However, in the presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate.

– Clarithromycin in combination with ranitidine bismuth citrate therapy is not recommended in patients with creatinine clearance less than 25 ml/min or in patients with a history of acute porphyria.

– BACTIMYCIN tablets and oral suspension can be taken with or without food and can be taken with milk.

Use in pregnancy and lactation:

Pregnancy (category c): Clarithromycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Lactation: Caution should be exercised when clarithromycin is administered to a nursing woman.

Pediatric use: Safety and effectiveness of clarithromycin in pediatric patients under 6 months of age have not been established. The safety of clarithromycin has not been studied in MAC patients under the age of 20 months.

Geriatric use: Dosage adjustment should be considered in elderly patients with severe renal impairment.

Drug interactions:

– Clarithromycin may increase ranitidine bismuth citrate concentration in serum. Concomitant using of Clarithromycin with ranitidine bismuth citrate is not recommended in patients with creatinine clearance less than 25 ml /min and should not be used in patients with a history of acute porphyria.

– Clarithromycin may be increase serum concentrations of theophyline and carbamazepine . Blood level monitoring of these medicines may be considered.

– Clarithromycin may potentiate the effects of the oral anticoagulants, like warfarin, Prothrombin times should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously.

– Clarithromycin may increase The steady-state plasma concentrations of omeprazole.

– Simultaneous oral administration of Clarithromycin and zidovudine to HIV-infected adult patients resulted in decreased steady-state zidovudine concentrations.

– Concomitant administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily lead to increase in the mean steady-state clarithromycin C _min and AUC of 33% and 18%, respectively.

– Simultaneous administration of clarithromycin tablets and didanosine to  HIV-infected adult patients result in no statistically significant change in didanosine pharmacokinetics.

– Concomitant administration of clarithromycin and tefenadine is contraindicated.

– Clarithromycin may be administered without dosage adjustment to patients with normal renal function taking ritonavir. However, for patients with renal impairment, the following dosage adjustments should be considered. For patients with CL CR 30 to 60 ml/min, the dose of clarithromycin should be reduced by 50%. For patients with CL CR < 30 ml/min, the dose of clarithromycin should be decreased by 75%.

– Serum digoxin concentrations should be carefully monitored while patients are receiving digoxin and clarithromycin simultaneously.

– Coadministration of erythromycin or clarithromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Blood level monitoring of these medicines may be considered. Examples of theses drugs:

1- Anti-arrhythmics like quinidine and disopyramide.

2- Anti-migraine drugs Ergotamine and dihydroergotamine

3- Triazolobenziodidiazepines (such as triazolam and alprazolam) and related benzodiazepines (such as midazolam).

4- HMG-CoA Reductase Inhibitors (e.g., lovastatin and simvastatin).

5- Sildenafil, cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, and bromocriptine.

– In addition, there have been reports of interactions of erythromycin or clarithromycin with drugs not thought to be metabolized by CYP3A including hexobarbital, phenytoin, and valproate.

– Concomitant administration of Bactimycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated.

Adverse reactions:

– The majority of side effects observed in clinical trials were of a mild and transient nature. The most frequently reported events in adults taking BACTIMYCIN were diarrhea , nausea , abnormal taste , dyspepsia, abdominal pain/discomfort , and headache . In pediatric patients, the most frequently reported events were diarrhea , vomiting , abdominal pain , rash , and headache.

• Post-marketing side effects that have been happened: Allergic reactions, glossitis, stomatitis, oral moniliasis, pancreatitis, tongue and tooth  discoloration, thrombocytopenia, leukopenia, dizziness, transient CNS events including anxiety, behavioral changes, confusional states,  Hepatic dysfunction, hypoglycemia, QT prolongation and ventricular arrhythmias.

Dosage and administration:

ADULTS:

– Pharyngitis/Tonsillitis due to S. pyogenes:  250 mg every 12 hours for 10 days.

– Acute maxillary sinusitis due to H. influenzae, M. catarrhalis, S. pneumoniae:   500 mg every 12 hours for 14 days.

– Acute exacerbation of chronic bronchitis due to:

– H. influenzae:500 mg every 12 hours for 7-14 days.

– H. parainfluenzae 500 mg every 12 hours for 7 days.

– M. catarrhalis 250 mg every 12 hours for 7-14 days.

– S. pneumoniae 250 mg every 12 hours for 7-14 days.

– Community-Acquired Pneumonia due to:

– H. influenzae 250 mg every 12 hours for 7 days.

– S. pneumoniae, C. pneumoniae, M. pneumoniae: 250 mg every 12 hours for 7-14 days.

– Uncomplicated skin and skin structure due to S. aureus, or S. pyogenes: 250 mg every 12 hours for 7-14 days.

– H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple therapy: BACTIMYCIN/lansoprazole/amoxicillin: 500 mg BACTIMYCIN, 30 mg lansoprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 or 14 days.

• Bactimycin/omeprazole/amoxicillin: 500 mg BACTIMYCIN, 20 mg omeprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 days. In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.

Dual therapy: BACTIMYCIN/omeprazole : 500 mg BACTIMYCIN given three times daily (q8h) and 40 mg omeprazole given once daily (qAM) for 14 days. An additional 14 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.

• BACTIMYCIN/ranitidine bismuth citrate: 500 mg BACTIMYCIN given twice daily (q12h) or three times daily (q8h) and 400 mg ranitidine bismuth citrate given twice daily (q12h) for 14 days. An additional 14 days of 400 mg twice daily is recommended for ulcer healing and symptom relief.

Children:  

The usual recommended daily dosage of clarithromycin oral suspension in children (  > 6 months) is 15 mg/kg/day divided q12h ( 7.5 mg / kg q12h)  for 10 days.

 

PEDIATRIC DOSAGE GUIDELINES Based on Body Weight Dosing Calculated on 7.5 mg / kg q12h
250 mg/5 mL	125 mg/5 mL	Dose (q12h)	Weight ( Kg)
1.25 mL q12h	2.5 mL q12h	62.5 mg	9
2.5 mL q12h	5 mL q12h	125 mg	17
3.75 mL q12h	7.5 mL q12h	187.5 mg	25
5 mL q12h	10 mL q12h	250 mg	33

Treatment and prophylaxis of Mycobacterial infections: Clarithromycin is the primary agent for the treatment of disseminated infection due to Mycobacterium avium complex. Clarithromycin should be used in combination with other antimycobacterial drugs that have shown activity in MAC treatment in vitro or clinically. The recommended dose for treatment and prophylaxis of mycobacterial infections in adults is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. Dosing recommendations for children are in the table above.

Dosage in liver and kidney impairement:

Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. However, in the presence of severe renal impairment (CR Cl < 30 ml/min), with or without coexisting hepatic impairment, the dose should be halved or the dosing interval doubled.

Overdosage:

– Overdosage of Bactimycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea.

– Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures.

– As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.

Storage:

– Store Bactimycin tablets at a temperature between 15-30 ° C.

– Store Bactimycin dry powder for oral suspension at a temperature between 15° – 30°C. After reconstitution, use within 14 days .Don’t refrigerate, Store at a temperature between 15° – 30°C.

– Shake the suspension well before each use.

Packing:

Tablets: A box contains 14 film-coated tablets.

Oral suspension: A bottle of 60 -100 ml, containing dry powder for oral suspension, with a syringe 5 ml.