Azithromycin, 500 mg 3 pcs

Interaction

Antacids do not affect bioavailability of azithromycin but decrease maximum blood concentrations by 30%; therefore, azithromycin should be taken at least one hour before or two hours after taking these drugs or a meal.

Asithromycin does not affect plasma concentrations of carbamazepine cimetidine didanosine efavirenz fluconazole indinavir midazolam triazolam trimethoprim/sulfamethoxazole cetirizine sildenafil and methylprednisolone when used simultaneously. Concomitant administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in concentrations of atorvastatin in plasma (on the basis of HMK-CoA reductase inhibition assay).

The concomitant use of azithromycin and rifabutin has no effect on the plasma concentrations of either drug. Neutropenia was sometimes observed when azithromycin and rifabutin were used concomitantly. Although neutropenia has been associated with the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

In a pharmacokinetic study involving healthy volunteers who received oral azithromycin (500 mg/day once daily) for three days followed by cyclosporine (10 mg/kg/day once daily) a significant increase in maximum plasma concentration and area under the concentration-time curve of cyclosporine was found. Caution should be exercised when using these drugs concomitantly.

If simultaneous use of these drugs is necessary, plasma concentrations of cyclosporine should be monitored and the dose should be adjusted accordingly.

Concomitant use of digoxin and azithromycin requires monitoring the plasma concentration of digoxin since many macrolides increase digoxin absorption in the intestine.

If simultaneous use with indirect anticoagulants (such as warfarin or other coumarin-type anticoagulants) is necessary, close monitoring of prothrombin time is recommended.

The concomitant use of terfenadine and macrolide class antibiotics has been found to cause arrhythmias and prolonged QT interval. Therefore, these complications cannot be excluded when terfenadine and azithromycin are taken concomitantly.

The concomitant use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times daily) causes increased equilibrium plasma concentrations of azithromycin. No clinically significant adverse effects have been observed and no dose adjustment of azithromycin with nelfinavir is required.

Asithromycin slightly interacts with cytochrome P450 isoenzymes; there are no known pharmacokinetic interactions similar to those with erythromycin and other macrolides. Azithromycin is neither an inducer nor an inhibitor of cytochrome P450 isoenzymes.

The interaction between azithromycin and theophylline has not been identified.

In concomitant use with zidovudine azithromycin does not affect pharmacokinetic parameters of zidovudine in blood plasma or excretion of it and its metabolite glucuronide by night. However, the concentration of the active metabolite phosphorylated zidovudine in mononuclear cells of peripheral vessels is increased. The clinical significance of this fact is not clear.

The simultaneous use of macrolides with ergotamine and dihydroergotamine may cause their toxic effects.

Persistent use of azithromycin with ergot alkaloid derivatives is not recommended because of the theoretical possibility of ergotism.

Special Instructions

In case of missing one dose of Azithromycin, the missed dose should be taken as soon as possible and the next ones should be taken 24 hours apart. The drug Azithromycin should not be used for treatment of pneumonia in patients for whom oral therapy cannot be given due to the severity of the disease and/or who have the following risk factors: cystic fibrosis bacteremia or suspected of it states which may change the body’s response to the course of the disease (immunodeficiency, functional asphyxia, etc) patients who need hospitalization aged or weakened patients.

The drug azithromycin should be used with caution in patients with mild to moderate hepatic impairment because of the possibility of fulminant hepatitis and severe hepatic failure.

In patients with symptoms of hepatic impairment, such as rapidly increasing asthenia jaundice darkened urine bleeding tendency hepatic encephalopathy, therapy with azithromycin should be discontinued and liver function testing should be performed.

In patients with renal dysfunction of mild to moderate degree (CK values over 40 ml/min) the treatment with Azithromycin should be carried out with caution under control of renal function status. In terminal renal failure (CKR less than 10 ml/min) there is a 33 % increase of azithromycin concentration in plasma.

Microbial resistance may develop if the recommended duration of therapy is not followed. As with other antibacterial agents during therapy with Azithromycin, patients should be regularly monitored for the presence of immune microorganisms and signs of superinfections, including fungal ones.

Asithromycin should not be used over a longer course than directed, since the pharmacokinetic properties of azithromycin suggest a short and simple dosing regimen.

Penicillin is usually the drug of choice for prophylaxis of pharyngitis/tonsillitis caused by Streptococcus pyogenes and also for prevention of acute rheumatic fever.

Azithromycin may cause pseudomembranous colitis caused by Clostridiumdifficile both as mild diarrhea and severe colitis with prolonged use. If diarrhea develops during treatment with Azithromycin, as well as 2 months after therapy termination, Clostridium pseudomembranous colitis should be excluded. The use of drugs inhibiting intestinal peristalsis is contraindicated.

Delayed ventricular repolarization syndrome – prolonged QT interval syndrome increases risk of arrhythmias including “pirouette” arrhythmias during macrolide therapy and also azithromycin. Caution should be exercised when using azithromycin in patients with prolonged QT receiving therapy with antiarrhythmic agents of class IA III cisapride if hypokalemia or hypomagnesemia is clinically significant arrhythmia bradycardia or severe heart failure.

We should use caution when using azithromycin concomitantly with antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin levofloxacin) cyclosporine and in elderly patients.

The use of azithromycin may provoke development of myasthenic syndrome or cause exacerbation of myasthenia gravis.

Effects on ability to control motor vehicle and machine:

When adverse effects on the nervous system and organs of vision develop, caution should be exercised while performing activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

– hypersensitivity to azithromycin erythromycin other ketolide macrolides or other components of the drug;

– severe hepatic impairment;

– severe renal impairment (creatinine clearance (CK) less than 40 ml/min);

– children under 12 years of age with body weight less than 45 kg (for 500 mg tablets);

– children under 3 years of age (for 125 mg tablets);

– breastfeeding period;

– concomitant administration with ergotamine and dihydroergotamine;

– lactose intolerance glucose-galactose malabsorption.

With caution:

Pregnancy; myasthenia; mild to moderate hepatic dysfunction; mild to moderate renal dysfunction (CK greater than 40 ml/min); elderly patients; in patients with proarrhythmogenic factors (especially in older patients): with congenital or acquired prolongation of the QT interval in patients receiving therapy with antiarrhythmic drugs of class IA (quinidine procainamide) III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin levofloxacin) with disorders of water andelectrolyte balance especially in case of hypokalemia or hypomagnesemia with clinically significant bradycardia, cardiac arrhythmia or severe heart failure; concomitant use of digoxin warfarin cyclosporine.

Side effects

The incidence of side effects is classified according to the World Health Organization recommendations: very frequently, at least 10%; frequently, at least 1% but less than 10%; infrequently, at least 01% but less than 1%; rarely, at least 001% but less than 01%; very rarely, less than 001% (including isolated cases).

Infectious diseases:

infrequent – candidiasis including oral and genital mucosa;

very rare – pseudomembranous colitis.

Metabolism and nutrition: often – anorexia.

Allergic reactions:

often – skin itching skin rash;

infrequent – hypersensitivity reactions photosensitivity reaction urticaria Stevens-Johnson syndrome angioedema;

very rare – anaphylactic reaction multiform erythema toxic epidermal necrolysis.

Blood and lymphatic system disorders:

often – eosinophilia lymphopenia;

infrequent – leukopenia neutropenia;

very rare – thrombocytopenia hemolytic anemia.

Respiratory system disorders:

infrequent – pneumonia pharyngitis respiratory diseases rhinitis dyspnea nasal bleeding.

Nervous system disorders:

often – headache dizziness paresthesia impaired sense of taste; infrequent – hypoesthesia drowsiness insomnia nervousness;

rarely – agitation;

very rare – anxiety aggression fainting seizures psychomotor hyperactivity loss of smell (or anosmia) and taste sensation myasthenia anxiety;

frequency unknown – perversion of smell delirium hallucinations.

An organ of vision: often – impairment of visual clarity.

Hearing organ and labyrinth disorders:

often – deafness;

infrequent – tinnitus hearing disorder;

rarely – vertigo.

Cardiovascular system disorders:

infrequent – sensation of palpitations “rushes” of blood to the skin of the face;

very rare – decreased blood pressure increased QT interval arrhythmia type “pirouette” ventricular tachycardia.

Gastrointestinal tract disorders:

very often – nausea flatulence abdominal pain diarrhea;

often – dyspepsia vomiting;

infrequent – constipation gastritis gastroenteritis dysphagia abdominal bloating dry oral mucosa belching oral mucosal ulcers increased salivary gland secretion;

very rare – discoloration of the tongue pancreatitis.

Liver and biliary tract disorders:

infrequent – increased activity of “hepatic” transaminases increased concentration of bilirubin hepatitis;

rare – impaired liver function;

very rare – cholestatic jaundice liver failure (in rare cases with fatal outcome mainly due to severe liver dysfunction) liver necrosis fulminant hepatitis.

Skin disorders:

infrequent dermatitis dry skin increased sweating.

Musculoskeletal and connective tissue disorders:

often – arthralgia;

infrequently – osteoarthritis myalgia back pain neck pain.

Toward the genitourinary system:

infrequent – increased concentration of urea and creatinine in plasma dysuria pain in the renal area metrorrhagia testicular function disorders;

very rare – interstitial nephritis acute renal failure. Laboratory parameters:

often – decreased plasma bicarbonate concentration increased number of: basophils monocytes neutrophils;

infrequent – increased number of platelets increased hematocrit; increased alkaline phosphatase activity increased chlorine increased plasma glucose concentration increased plasma bicarbonate concentration changed plasma sodium concentration changed potassium concentration.

Other:

often – weakness;

infrequent – chest pain peripheral edema asthenia malaise feeling of fatigue facial edema fever.

Overdose

Symptoms: nausea temporary hearing loss vomiting diarrhea.

Treatment: symptomatic.

Pregnancy use

Azithromycin is used during pregnancy only when the benefit to the mother outweighs the possible risk to the fetus. Breastfeeding should be suspended during treatment with azithromycin.

Similarities

Azithromycin, Chemomycin, Azitral, Zifactor, Azitrox, Ecomed (Azithromycin), Sumamed, AzitRus, Sumamed forte, Zitrolide forte