Myazi

Rx                 MYAZI

COMPOSITION:

MYAZI 1 TAB

Each film coated tab contains

Azithromycin IP             500mg

DESCRIPTION:

Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics. It is derived from erythromycin, with a methyl-substituted nitrogen atom incorporated into the lactone ring, thus making the lactone ring 15-membered.

Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L­ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C₃₈H₇₂N₂O₁₂, and its molecular weight is 749.0. Azithromycin has the following structural formula:

PHARMACODYNAMICS:

Mechanism of Action

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and, thus, interfering with microbial protein synthesis. Nucleic acid synthesis is not affected.

PHARMACOKINETICS

Absorption:

After oral administration the bioavailability of azithromycin is approximately 37%. Peak plasma levels are reached after 2-3 hours (C_max after a single dose of 500 mg orally was approximately 0.4 mg/l).

Distribution:

Kinetic studies have shown markedly higher azithromycin levels in tissue than in plasma (up to 50 times the maximum observed concentration in plasma) indicating that the active substance is heavily tissue bound (steady state distribution volume of approximately 31 l/kg). Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC₉₀for likely pathogens after a single dose of 500 mg.

In experimental in vitro and in vivo studies azithromycin accumulates in the phagocytes, freeing is stimulated by active phagocytosis. In animal studies this process appeared to contribute to the accumulation of azithromycin in the tissue.

In serum the protein binding of azithromycin is variable and depending on the serum concentration varies from 50% in 0.05 mg/l to 12% in 0.5 mg/l.

Metabolism:

Liver (demethylation).

Excretion:

Via the bile (as unchanged drug and metabolites); via the urine (6% of the dose). Elimination half-life: about 68 hr.

Plasma concentrations of azithromycin following single 500 mg oral and i.v. doses declined in a polyphasic pattern with a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hours. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.

Pharmacokinetics in special populations

Renal insufficiency

Following a single oral dose of azithromycin 1 g, mean C_max and AUC_0-120 increased by 5.1% and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate of 10-80 ml/min) compared with normal renal function (GFR > 80 ml/min). In subjects with severe renal impairment, the mean C_max and AUC_0-120 increased 61% and 33% respectively compared to normal.

Hepatic insufficiency

In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to normal hepatic function. In these patients, urinary recovery of azithromycin appears to increase perhaps to compensate for reduced hepatic clearance.

Elderly

The pharmacokinetics of azithromycin in elderly men was similar to that of young adults; however, in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no significant accumulation occurred.

Infants, toddlers, children and adolescents

Pharmacokinetics have been studied in children aged 4 months – 15 years taking capsules, granules or suspension.. At 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the C_max achieved is slightly lower than adults with 224 ug/l in children aged 0.6-5 years and after 3 days dosing and 383 ug/l in those aged 6-15 years. The t_1/2 of 36 h in the older children was within the expected range for adults.

Indications:

Adults:

Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

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

Acute bacterial otitis media (adequately diagnosed)

Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae,

Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy.

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.

NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. MYAZI is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to Azithromycin, susceptibility tests should be performed when patients are treated with Azithromycin. Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.

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

Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae.

Genital ulcer disease in men due to Haemophilus ducreyi (chancroid). Due to the small number of women included in clinical trials, the efficacy of azithromycin in the treatment of chancroid in women has not been established.

CONTRAINDICATIONS:

Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic.

WARNING AND PRECAUTIONS:

Azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients.

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome has been reported in patients receiving azithromycin therapy. Prescribing Azithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

In patients receiving ergotamine derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergotamine derivatives and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered

USE IN PREGNANCY AND LACTATION:

Recent clinical studies have recommended that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy. In other infections, azithromycin should be used only when clearly needed. It is not known whether azithromycin is excreted in breast milk. Exercise caution when administering to a nursing woman.

DRUG INTERACTIONS:           

Antacids: Peak serum levels but not the total extent of absorption is reduced by aluminium - and magnesium - containing antacids in the stomach. Azithromycin should therefore be taken at least 1 hour before or 2 hours after taking these antacids.

Ergot Derivatives: Because of the theoretical possibility of ergotism, concomitant administration of ergot derivatives and azithromycin should be avoided.

Digoxin & Cyclosporin: Macrolides have been known to increase the plasma concentration of Digoxin & Cyclosporin and so caution should be exercised while co-administration is necessary.

Anti-Histamines: A potentially life threatening interaction between erythromycin and terfenadine or astemizole have been reported. Although such an interaction with azithromycin is not established yet and undergoing clinical study, so it is wise to avoid concomitant use of azithromycin and terfenadine or astemizole.

There have been no pharmacokinetic drug interactions between azithromycin and warfarin, theophylline, carbamazepine, methylprednisolone and cimetidine.

In clinical trials, around 45% patients receiving azithromycin also received other drugs concomitantly, e.g. bronchodilators, analgesics, corticosteroids, diuretics, anxiolytics and antiarthritic drugs. No drug interaction problems were encountered.

ADVERSE EFFECTS:

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients from the multiple-dose clinical trials discontinued Azithromycin therapy because of treatment-related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. Rarely but potentially serious side effects were angioedema and cholestatic jaundice.

Clinical

Multiple-dose regimen

Overall, the most common side effects in adult patients receiving a multiple-dose regimen of Azithromycin were related to the gastrointestinal system with diarrhea/loose stools (5%), nausea (3%), and abdominal pain (3%) being the most frequently reported.

No other side effects occurred in patients on the multiple-dose regimen of Azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following:

Cardiovascular: Palpitations, chest pain.
Gastrointestinal: Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice.
Genitourinary: Monilia, vaginitis, and nephritis.
Nervous System: Dizziness, headache, vertigo, and somnolence.
General: Fatigue.
Allergic: Rash, photosensitivity, and angioedema.

DOSAGE AND ADMINISTRATION:

For Otitis media and skin and soft tissue infections

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Adult: 500 mg once daily for 3 days. Alternatively, 500 mg as a single dose on the 1st day followed by 250 mg once daily for 4 days.

Child: >6 mth: 10 mg/kg; 15–25 kg: 200 mg; 26–35 kg: 300 mg; 36–45 kg: 400 mg. Doses to be taken once daily for 3 days

For lower respiratory tract infections including bronchitis and pneumonia, upper respiratory tract infections including sinusitis and pharyngitis/tonsillitis,

Adult: 500 mg once daily for 3 days. Alternatively, 500 mg as a single dose on the 1st day followed by 250 mg once daily for 4 days.

Child: >6 mth: 10 mg/kg; 15–25 kg: 200 mg; 26–35 kg: 300 mg; 36–45 kg: 400 mg. Doses to be taken once daily for 3 days

For sexually transmitted diseases caused by Chlamydia trachomatis , the dose of Myazi is

Adult: 1 g as a single dose.

Uncomplicated gonorrhoea
Adult: 2 g as a single dose.

Prophylaxis of disseminated MAC infections

Adult: 1.2 g once every wk. For treatment or secondary prophylaxis: 500 mg once daily with other antimycobacterials.
Child: >6 mth: 10 mg/kg once daily for 3 days.

Granuloma inguinale

Adult: Initially, 1 g followed by 500 mg daily. Alternatively, 1 g once a wk for at least 3 wk, until all lesions have completely healed.

Active immunisation against typhoid fever caused by Salmonella typhi
Adult: 500 mg once daily for 7 days.

Use in the elderly

Normal adult dosage is recommended. Children: The dose of Myazi in children over 6 months of age is 10 mg/kg body weight once daily for 3 days. Alternatively, 10 mg/kg on day 1, followed by 5 mg/kg for next 4 days is also recommended. There is no information on use of Myazi.

Azithromycin on children under 6 months of age. For children with body weight 15-25 kg (3-7 years), the dose is 200 mg once daily for 3 days; for body weight 26-35 kg (8-11 years), the dose is 300 mg once daily for 3 days; for body weight 36-45 kg (12-14 years), the dose is 400 mg once daily for 3 days. For body weights over 45 kg, normal adult dosage is recommended.

OVERDOSAGE:

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

STORAGE:
Store in a cool and dry place

COMMERCIAL PACKAGING:

MYAZI is available in a blister of 5 Tablets.

Each box of MYAZI contains 10 X 5’s