Azithromycin (AZT) is macrolide antibiotics, it is [9-de-oxy-9a-aza-9a-methyl-9a-homoerythromycin A dihydrate] is an Azalide. It inhibits protein synthesis by binding 50S ribosomal subunit of the bacteria.
Indications:
Cefixime Trihydrate:
● Lower Respiratory Tract Infections
● Pharyngitis and tonsilitis
● Acute sinusitis
● Gnorrhea and associated infections
● Acute Urinary Tract Infections
● Acute Otitis Media
● Helicobacter pylori infection
● Lyme disease
● Salmonlella and shigella infections.
Azithromycin:
● Otitis media
● Respiratory tract infection
● Cystic fibrosis
● Anti-inflammatory in COPD Patient
● In P. Falciparum Malaria with other Antimalarial drugs
● Typhoid fever
● Neissaria gonorrhoeae.
Rationale of Combination:
Product Description:
A new combination of cefixime and azithromycin is used for the treatment of upper and lower respiratory tract infection.Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. Whereas Azithromycin due to it's long half life, which enables once daily dosing and shorter administration durations, is a property distinct from other macrolides.
Pharmacology:
Cefixime Trihydrate:
Absorption: About 40% to 50% is absorbed. C maxfollowing 200 and 400 mg doses of oral suspension are 3 and 4.6 mcg/mL, respectively. T max occurs between 2 and 6 h following administration of 400 mg and between 2 and 5 h after a 200 mg dose.
Distribution: Protein binding is about 65%.
Elimination About 50% of absorbed dose is excreted unchanged in the urine in 24 h. Serum t ½averages 3 to 4 h, but may be as long as 9 h in some healthy subjects.
Azithromycin:
Absorption: Following oral administration, azithromycin is rapidly absorbed and widely distributed throughout the body. Bioavailability is 37% following oral administration. Absorption is not affected by food.
Distribution: Azithromycin is extensively distributed in tissues with tissue concentrations reaching up to 50 times greater than plasma concentrations. Drug becomes concentrated within macrophages and polymorphonucleocytes giving it good activity against Chlamydia trachomatis.
Elimination: Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. The Half life being 68 hours.
Mechanism of Action:
Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.
On the other hand, like other macrolide antibiotics, azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of the bacterial 70S ribosome. Binding inhibits peptidyl transferase activity and interferes with amino acid translocation during the process of translation. Its effects may be bacteriostatic or bactericidal depending of the organism and the drug concentration.
Adverse Effects:
● Diarrhea that is watery or bloody.
● Chest pain, uneven heartbeats.
● Nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
● Severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin.
Contraindications:
Known hypersensitivity to cefixime or other cephalosporins. Contraindicated in patients with a history of liver disease, kidney disease and also muscle disease.
Drug Interactions:
●Carbamazepine: Elevated carbamazepine levels have been reported in postmarketing experience when cefixime is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations.
●Warfarin and Anticoagulants: Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly.
Although most antibiotics probably do not affect hormonal birth control such as pills, patch, or ring, some antibiotics may decrease their effectiveness. This could cause pregnancy. Examples include rifamycins such as rifampin or rifabutin. Be sure to ask your doctor or pharmacist if you should use additional reliable birth control methodswhile using this antibiotic.
The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using azithromycin, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).
Precautions:
● Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function.
● Take this medication by mouth, with or without food. You may take this medication with food if stomach upset occurs.
● During pregnancy, this medication should be used only when clearly needed.