Azithromycin Dihydrate IP 500 mg Tablet

Talk with your doctor or pharmacist before taking Azithromycin if:

You have severe liver or kidney problems.

You have severe heart problems or problems with your heart beat such as long QT syndrome (shown on an electro-cardiogram or ECG machine).

Your blood levels of potassium or magnesium are too low.

You develop signs of another infection.
you are taking any ergot derivatives such as ergotamine (to treat migraine) as these medicines should not be taken together with azithromycin.

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking azithromycin it is important that your doctor or pharmacist knows:

If you are pregnant or breast-feeding.

If you have any problems with the way your liver works or the way your kidneys work.

If you know you have an unusual heart rhythm.

If you have a muscle disorder called myasthenia gravis.

If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, such as herbal and complementary medicines.

If you have ever had an allergic reaction to a medicine.

These are usually mild to moderate, and stop when treatment is stopped.If you suffer from any of the following side effects, and either tell your doctor IMMEDIATELY . You may be experiencing a rare severe allergic reaction to the tablets:

Swelling of the hands, feet, ankles, face, lips, mouth or throat

Problems with swallowing or breathing

Serious skin reactions including Stevens-Johnson Syndrome (a severe skin rash) and other severe skin rashes which may involve blistering or peeling (these may be severe allergic reactions)

Severe, persistent diarrhoea especially if it has blood or mucus in it (this may be Pseudo membranous colitis).

This is a Prefered Dosage:
Always take Azithromycin 250mg exactly as your doctor has prescribed you. You should check with your doctor or pharmacist if you are not sure.
Adults: Respiratory tract and skin or soft tissue infections: 500 mg once daily for three days.
Sexually transmitted diseases: 1000 mg as a single dose.
Elderly: The usual adult doses may be used.
Children: Azithromycin 250mg tablets are not recommended for use in children weighing less than 45 kg. For children weighing more than 45 kg the usual adult dose may be used.

Disclaimer:To be taken only after consulting with the doctor.

PHARMACOLOGY

Mechanism of Action

Azithromycin is a macrolide antibacterial drug. Azithromycin concentrates in phagocytes and fibroblasts as demonstrated byin vitro incubation techniques. Using such methodology, the ratio ofintracellular to extracellular concentration was > 30 after one hour of incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Pharmacodynamics

Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens (S. pneumoniae and S. aureus). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin.

Pharmacokinetics

Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC0-72 = 4.3 (1.2) mcg•h/mL; Cmax = 0.5 (0.2) mcg/mL; Tmax = 2.2 (0.9) hours. With a regimen of 500 mg (two 250 mg tablets*) on day 1, followed by 250 mg daily (one 250 mg capsule) on days 2 through 5, the pharmacokinetic parameters of azithromycin in plasma in healthy young adults (18 to 40 years of age) are portrayed in the chart below. Cmin and Cmaxremained essentially unchanged from day 2 through day 5 of therapy.

Absorption: The absolute bioavailability of azithromycin 250 mg tablets is 38%.In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase Cmax by 23% but had no effect on AUC. When azithromycin suspension was administered with food to 28 adult healthy male subjects, C_max increased by 56% and AUC was unchanged.The AUC of azithromycin was unaffected by coadministration of an antacid containing aluminum and magnesium hydroxide with azithromycin tablets; however, the Cmax was reduced by 24%. Administration of cimetidine (800 mg) two hours prior to azithromycin had no effect on azithromycin absorption.
Distribution: The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL. Following oral administration, azithromycin is widely distributed throughout the body with an apparent steady-state volume of distribution of 31.1 L/kg. Greater azithromycin concentrations in tissues than in plasma or serum were observed. High tissue concentrations should not be interpreted to be quantitatively related to clinical efficacy. The antimicrobial activity of azithromycin is pH related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity.
Metabolism: In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.
Elimination: 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. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.

INTERACTIONS

Drug interaction studies were performed with azithromycin and other drugs likely to be coadministered .When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenous and oral), triazolam, trimethoprim/sulfamethoxazole or zidovudine. Coadministration with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. No dosage adjustment of either drug is recommended when azithromycin is coadministered with any of the above agents.
Interactions with the drugs listed below have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, they have been observed with macrolide products. Until further data are developed regarding drug interactions when azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised:
Digoxin elevated digoxin concentrations.
Ergotamine or dihydroergotamine acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
Terfenadine, cyclosporine, hexobarbital and phenytoin concentrations.

Information for Patients:
Azithromycin Tablets can be taken with or without food. Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously.
The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.
Patients should be counseled that antibacterial drugs including Azithromycin Tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azithromycin Tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Azithromycin Tablets or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Azithromycin Tablets contain the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for oral administration. 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-L - ribo- 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.