KMZITH 500 TABLETS

Indications

• Bacterial infections
• Mild to moderate typhoid due to multiple-antibacterial resistant organisms
• Respiratory-tract infections
• Otitis media
• Skin and soft tissue infections
• Chlamydia trachomatis genital infection
• Chronic Pseudomonas aeruginosa infection in cystic fibrosis
• Prevention of group A streptococcal infection in patients allergic to penicillin

Dosage

Children: Child 6 months–17 years: 10 mg/kg once daily (max. per dose 500 mg) for 3 days, repeated after 1 week if necessary. Refer to BNF for Children for specific dosing based on age and weight.

Adults: 500 mg once daily for 3 to 5 days depending on the infection being treated. For certain cases, doses may be adjusted based on clinical judgment.

Mechanism of action

Azithromycin binds to the 50S ribosomal subunit of bacteria, inhibiting protein synthesis and thus preventing bacterial growth.

Pharmacodynamics

Azithromycin exhibits bacteriostatic activity against susceptible bacteria. It has a long half-life, allowing for once-daily dosing and effective treatment of infections.

Pharmacokinetics

Azithromycin is well-absorbed after oral administration, with a bioavailability of approximately 37%. It penetrates well into tissues, with a half-life of about 68 hours, and is primarily excreted in bile, with minimal renal excretion.

Adverse effects

• Appetite decreased
• Diarrhoea
• Dizziness
• Gastrointestinal discomfort
• Headache
• Hearing impairment
• Insomnia
• Nausea
• Pancreatitis
• Paraesthesia
• Skin reactions
• Taste altered
• Vomiting
• Angioedema
• Anxiety
• Arrhythmias
• Chest pain
• Constipation
• Drowsiness
• Eosinophilia
• Hepatic disorders
• Leucopenia
• Neutropenia
• Palpitations
• QT interval prolongation
• Severe cutaneous adverse reactions (SCARs)
• Tinnitus
• Vertigo
• Antibiotic associated colitis
• Myasthenia gravis
• Nephritis tubulointerstitial
• Hallucination
• Hypotension
• Seizure
• Acute kidney injury
• Aggression
• Akathisia
• Hemolytic anemia
• Syncope

Interactions

• Azithromycin + ticagrelor: Moderate (increases exposure)
• Azithromycin + aliskiren: Unknown (increases exposure)
• Azithromycin + aminophylline: Unknown (increases exposure)
• Azithromycin + colchicine: Unknown (increases exposure)
• Azithromycin + erlotinib: Unknown (increases exposure)
• Azithromycin + lomitapide: Unknown (increases exposure)
• Azithromycin + rimegepant: Unknown (increases exposure)
• Azithromycin + taxanes: Unknown (increases exposure)
• Azithromycin + docetaxel: Unknown (increases exposure)
• Azithromycin + paclitaxel: Unknown (increases exposure)

Precautions

• Use with caution in patients with electrolyte disturbances
• Use with caution if estimated glomerular filtration rate is less than 10 mL/minute/1.73 m2
• Predisposition to QT interval prolongation may be aggravated

Dosage

Children: Refer to specific drug guidelines for dosing, as it varies based on the active ingredient and formulation.

Adults: Refer to specific drug guidelines for dosing, as it varies based on the active ingredient and formulation.

Mechanism of action

The mechanism of action for dihydrated compounds varies widely depending on the specific drug. Generally, dihydrates enhance the solubility of the active ingredient, leading to improved absorption in the gastrointestinal tract. This increased bioavailability can be critical for the drug's therapeutic efficacy.

Pharmacodynamics

Pharmacodynamics refers to the effects and mechanisms of action of a drug on the body. For dihydrates, the pharmacodynamics will depend on the active drug it carries. Dihydrated molecules may exhibit enhanced activity due to better solubility and absorption, allowing them to reach therapeutic concentrations more effectively. The specific pharmacodynamic profile will vary based on the individual drug's properties.

Pharmacokinetics

Pharmacokinetics describes how the body absorbs, distributes, metabolizes, and excretes a drug. Dihydrated forms can influence these parameters, primarily enhancing absorption due to increased solubility. The onset of action, peak plasma concentration, and elimination half-life can be affected, leading to variations in dosing regimens and therapeutic monitoring outcomes.

Pregnancy

Safety has not been established; use only if clearly needed.

Breast-feeding

Caution is advised; consult a healthcare professional.

Storage

Store in a cool, dry place, away from direct light.

Mechanism of action

In order to replicate, bacteria require a specific process of protein synthesis, enabled by ribosomal proteins. Azithromycin binds to the 23S rRNA of the bacterial 50S ribosomal subunit. It stops bacterial protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit,. This results in the control of various bacterial infections,. The strong affinity of macrolides, including azithromycin, for bacterial ribosomes, is consistent with their broad‐spectrum antibacterial activities. Azithromycin is highly stable at a low pH, giving it a longer serum half-life and increasing its concentrations in tissues compared to erythromycin. Azithromycin usually is bacteriostatic, although the drug may be bactericidal in high concentrations against selected organisms. Bactericidal activity has been observed in vitro against Streptococcus pyogenes, S. pneumoniae, and Haemophilus influenzae. Azithromycin inhibits protein synthesis in susceptible organisms by penetrating the cell wall and binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. The site of action of azithromycin appears to be the same as that of the macrolides (i.e., erythromycin, clarithromycin), clindamycin, lincomycin, and chloramphenicol. The antimicrobial activity of azithromycin is reduced at low pH. Azithromycin concentrates in phagocytes, including polymorphonuclear leukocytes, monocytes, macrophages, and fibroblasts. Penetration of the drug into phagocytic cells is necessary for activity against intracellular pathogens (e.g., Staphylococcus aureus, Legionella pneumophila, Chlamydia trachomatis, Salmonella typhi).

Pharmacodynamics

Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections. Azithromycin has additional immunomodulatory effects and has been used in chronic respiratory inflammatory diseases for this purpose.