AZIQUE TABLETS

Indications

• Bacterial infections of the respiratory tract
• Skin and soft tissue infections
• Otitis media
• Sinusitis
• Chlamydia infections
• Mycobacterial infections

Dosage

Children: Refer to the BNF for Children for age-appropriate dosing information.

Adults: Refer to the BNF for specific dosing information based on the infection being treated.

Mechanism of action

Azithromycin exerts its antibacterial effects by binding to the 50S ribosomal subunit of susceptible bacteria, inhibiting RNA-dependent protein synthesis. This action disrupts the translocation process of the growing peptide chain, leading to the cessation of protein production, which is essential for bacterial survival.

Pharmacodynamics

The pharmacodynamic properties of azithromycin involve its ability to achieve high tissue concentrations and a long half-life, allowing for once-daily dosing. Azithromycin exhibits time-dependent antimicrobial activity, which means that the duration of exposure of the bacteria to the drug is more important than the peak concentration achieved.

Pharmacokinetics

Azithromycin is well-absorbed after oral administration, with an oral bioavailability of approximately 37%. It is widely distributed throughout the body, including to tissues such as lungs and tonsils. The drug is primarily metabolized in the liver and has a terminal half-life of approximately 68 hours, allowing for sustained antibacterial activity even after the course of therapy has ended. Azithromycin is excreted in the bile, with minimal renal excretion.

Contra-indications

• Hypersensitivity to azithromycin, erythromycin or any macrolide antibiotic
• Severe hepatic impairment
• History of cholestatic jaundice/hepatic dysfunction with prior use of azithromycin

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Abdominal pain
• Headache
• Dizziness
• Rash
• QT prolongation
• Hepatotoxicity
• Allergic reactions (urticaria, anaphylaxis)

Interactions

• May increase the effects of warfarin, leading to increased bleeding risk
• Concurrent use with ergot derivatives may cause ergotism
• May reduce the efficacy of oral contraceptives
• Caution with drugs that prolong the QT interval

Precautions

• Use with caution in patients with pre-existing liver disease
• Monitor for signs of allergic reactions
• Caution in patients with renal impairment
• Assess for history of arrhythmias or cardiac disease

Pregnancy

Azithromycin is generally considered safe during pregnancy. However, it should be used only if clearly needed and after assessing potential benefits and risks.

Breast-feeding

Azithromycin is excreted in breast milk. Caution is advised when administering to nursing mothers, as effects on the infant are unknown.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets (250 mg, 500 mg)
• Oral suspension (100 mg/5 mL, 200 mg/5 mL)
• Intravenous injection (500 mg)

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

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.