Zithromax

General information

Zithromax is an antibacterial agent from the group of macrolides, effective against a wide range of bacterial infections. The drug is used for treatment of respiratory tract, skin, soft tissues and other infectious processes caused by sensitive microorganisms.

Trade name

Zithromax

International Nonproprietary Name (INN)

Azithromycin

Form of release

The drug is available in the following forms:

• Film-coated tablets: 250 mg and 500 mg
• Capsules: 250 mg.
• Powder for preparation of suspension for oral administration: 100 mg/5 ml and 200 mg/5 ml (vials 15 ml, 30 ml).
• Liofilizate for preparation of solution for infusion: 500 mg (vials).

Constitution

Acting substance

Azithromycin (in the form of dihydrate).

Auxiliary components

The composition varies depending on the form of release:

• Tablets: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose (shell), titanium dioxide, lactose monohydrate.
• Capsules: corn starch, magnesium stearate, gelatin (shell), titanium dioxide.
• Powder for suspension: sucrose, sodium phosphate, xanthan gum, flavoring (cherry or banana).
• Lyophilizate: sodium hydroxide, citric acid (for pH adjustment).

Pharmacologic properties

Pharmacodynamics

Zithromax has bacteriostatic action, which is realized by inhibiting protein synthesis in bacterial cells. Azithromycin binds to 50S-subunit of microorganisms ribosomes, preventing translocation of peptide chains and disrupting the process of formation of functional proteins necessary for bacterial life. The drug is active against a wide range of pathogens, including Gram-positive (Streptococcus pneumoniae, Staphylococcus aureus), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) bacteria, as well as atypical microorganisms (Chlamydia pneumoniae, Mycoplasma pneumoniae).

In high concentrations reached in the centers of infection, the drug can exhibit a bactericidal effect, especially against sensitive strains. Due to the ability to accumulate inside cells, including phagocytes, Zithromax is effectively delivered to the site of inflammation, which enhances its action in respiratory tract and tissue infections. Its prolonged post-antibiotic action allows the use of short courses of treatment, maintaining therapeutic efficacy after the end of dosing.

Pharmacokinetics

Azithromycin is well absorbed from the gastrointestinal tract after oral administration, reaching maximum concentration in blood plasma in 2-3 hours. Bioavailability is about 37%, which is due to partial degradation in the acidic environment of the stomach. Food intake reduces absorption, therefore it is recommended to take the drug 1 hour before a meal or 2 hours after. When administered intravenously, bioavailability reaches 100%, and peak concentration is observed immediately after infusion.

The drug is widely distributed in tissues and body fluids, demonstrating a volume of distribution of about 31 L/kg. It accumulates in high concentrations in the lungs, tonsils, skin and mucous membranes, exceeding plasma levels by 10-100 times. Binding to plasma proteins is 7-50% and decreases with increasing concentration. Metabolism occurs in the liver with the participation of demethylation enzymes, forming inactive metabolites.

The half-life of azithromycin varies from 68 to 72 hours, which is due to its slow release from tissues. The main route of excretion is through bile with feces (about 50% in unchanged form), about 6-12% is excreted by kidneys. In patients with impaired hepatic or renal function, elimination may be delayed, but dose adjustment is required only in severe cases.

Indications for use

Diseases and conditions for which the drug is prescribed

Zithromax is prescribed for the treatment of the following infectious diseases caused by sensitive microorganisms:

• Infections of the upper respiratory tract: pharyngitis, tonsillitis, sinusitis
• Lower respiratory tract infections: bronchitis, community-acquired pneumonia.
• Infections of the skin and soft tissues: rye, impetigo, secondary infected dermatoses.
• Ear infections: otitis media (especially in children).
• Sexually transmitted infections: uncomplicated urethritis and cervicitis caused by Chlamydia trachomatis.
• Lyme disease (initial stage - erythema migrans).
• Infections of the gastrointestinal tract: gastroenteritis caused by Campylobacter jejuni (as part of a complex therapy).

Contraindications

Conditions under which the use of the drug is prohibited

The use of Zithromax is prohibited in the following conditions:

• Hypersensitivity to azithromycin, other macrolides (e.g., erythromycin), or any excipients of the drug.
• Severe hepatic insufficiency (Child-Pugh class C), as the drug is metabolized in the liver.
• Combined use with drugs that prolong the QT interval (e.g., cisapride) because of the risk of arrhythmias.
• Severe electrolyte imbalances (hypokalemia, hypomagnesemia), increasing the risk of cardiac complications.
• Children under 6 months of age (for suspension) or under 12 years of age with body weight less than 45 kg (for tablets and capsules).

How to use and dosage

How to take

Zithromax is taken orally or administered intravenously depending on the form of release. Tablets and capsules should be swallowed whole, drinking enough water (100-200 ml), 1 hour before a meal or 2 hours after to avoid decreased absorption. The suspension is prepared by adding water to the vial up to the indicated mark, shake before each administration and drink with water. The lyophilizate for infusion is diluted in an appropriate solution (0.9% sodium chloride or 5% glucose) and administered slowly under the supervision of medical personnel.

Dosages for adults and children

Adults

Dosage depends on the indication:

• Infections of the respiratory tract, skin: 500 mg on the first day, then 250 mg once daily from day 2 through day 5 (total course 1.5 g).
• Chlamydia infections: 1 g once.
• Lyme disease: 1 g on the first day, then 500 mg once daily from the 2nd to the 5th day.
• Intravenous (severe infections): 500 mg once daily for 1-2 days, then switch to oral administration.

Children

Dosage is calculated by body weight (for children over 6 months of age):

• Suspension: 10 mg/kg on the first day, then 5 mg/kg once daily from day 2 through day 5.
• Tablets/capsules (body weight >45 kg): as in adults - 500 mg on the first day, then 250 mg from day 2 through day 5.
• Otitis or pneumonia: 10 mg/kg once on the first day, then 5 mg/kg per day for 2-5 days.

Dose adjustment for certain conditions

Dose adjustment is not required in renal insufficiency (creatinine clearance >10 ml/min), as excretion through the kidneys is minimal. In severe hepatic insufficiency (Child-Pugh class C) the drug is contraindicated, and in moderate hepatic insufficiency (class B) the dose is reduced by 50% with liver function monitoring. In elderly patients the dosage is kept standard, but monitoring of cardiac status and electrolyte balance is required.

Side effects

Possible adverse reactions of the body

The following adverse reactions may occur during the use of Zithromax:

• Side of the digestive system: nausea, diarrhea, abdominal pain, vomiting, flatulence, rarely - increase in the activity of liver enzymes.
• Nervous system disorders: headache, dizziness, drowsiness, insomnia.
• Cardiovascular system: palpitations, prolongation of the QT interval (especially with predisposition).
• Allergic reactions: skin rash, itching, urticaria, in rare cases - angioedema.
• Hearing organs: reversible hearing loss, tinnitus (with prolonged use).
• Other: weakness, candidiasis of mucous membranes, taste changes.

Overdose

Symptoms of overdose

The following symptoms may occur if the recommended dose of Zithromax is exceeded:

• Gastrointestinal disorders: severe nausea, vomiting, diarrhea.
• Nervous system disorders: dizziness, confusion.
• Hearing disorders: temporary hearing loss or tinnitus.
• Cardiovascular disorders: palpitations, rarely - arrhythmias.

First aid measures

In case of suspected overdose it is necessary:

1. Stop taking the drug.
2. Seek medical attention.
3. Rinse the stomach, if the intake has occurred recently (within 1-2 hours).
4. Give activated charcoal (1 g/kg body weight) to reduce absorption.
5. Provide symptomatic treatment: hydration, cardiac and respiratory control until the arrival of a doctor.

Interaction with other drugs

Influence on the effects of other drugs

Zithromax may alter the effects of other medicines:

• Exacerbates the toxicity of drugs that prolong the QT interval (e.g., antiarrhythmics such as amiodarone), increasing the risk of arrhythmias.
• Elevates the concentration of CYP3A4 substrates (e.g., cyclosporine, warfarin) when co-administered, requiring monitoring of their levels in the blood.
• Decreases the effectiveness of antacids (aluminum- or magnesium-containing) if taken concomitantly; an interval of at least 2 hours is recommended.
• Enlarges the risk of side effects when combined with ergotamines (e.g., ergotamine), causing vasospasms.
• No significant effect on theophylline metabolism, but individual reactions are possible.

Compatibility with alcohol and food

Alcohol consumption during treatment with Zithromax is undesirable, as it may increase side effects such as nausea and dizziness, as well as delay recovery in infections. Food reduces the absorption rate of the drug, so it is recommended to take it 1 hour before a meal or 2 hours after for optimal effectiveness.

Special Instructions

Use in pregnancy and breastfeeding

Zithromax is used during pregnancy only when the expected benefit to the mother exceeds the potential risk to the fetus, as safety data are limited. The drug penetrates the placental barrier, but teratogenic effects have not been confirmed. During breastfeeding azithromycin is excreted with milk in small amounts; if treatment is necessary, it is recommended to temporarily discontinue feeding or choose an alternative drug.

Effects on driving and mechanisms

The drug may cause side effects such as dizziness, drowsiness or weakness, especially at the beginning of treatment. Patients should refrain from driving vehicles and working with mechanisms until the individual reaction to Zithromax is clear and the effect on concentration is not excluded.

Particularities of use in the elderly and children

In elderly patients Zithromax is used in standard doses, but caution is required due to possible risk of QT interval prolongation and decrease in liver or kidney function; cardiac activity monitoring is recommended. In children the drug is used from 6 months of age (suspension) or from body weight of 45 kg (tablets/capsules), the dosage is selected strictly according to weight to avoid overdose and side effects.