AzitroLek: composition and pharmaceutical form
AzitroLek is a powder from which a suspension is prepared before use. Every 5 ml of the reconstituted suspension contains 102.4 or 204.8 mg of azithromycin monohydrate, which corresponds to 100 or 200 mg of azithromycin.
The powder is mixed with water until a uniform white or almost white suspension is obtained. It is measured with a polyethylene-polypropylene oral syringe: the syringe comes with the pack and is more accurate than any household spoon. The whole daily dose is given at once, and food does not interfere with it. The suspension tastes bitter, and that aftertaste may be softened by drinking fruit juice after the medicine.
How AzitroLek works
Azithromycin belongs to the azalides, a subgroup of macrolide antibiotics. It attaches to the 50S subunit of the bacterial ribosome and blocks the movement of peptide chains from one side of the ribosome to the other. RNA-dependent protein assembly stops at that point: the bacterium stays alive but ceases to build its own proteins and to multiply.
The reverse side of this mechanism is resistance, and with azithromycin it may be either inherited or acquired. Three ways are known in which bacteria escape the drug: they change the target itself, they change the transport of the antibiotic into the cell, or they modify the antibiotic molecule. In certain strains of Streptococcus pneumoniae, group A β-haemolytic streptococci, Enterococcus faecalis and Staphylococcus aureus, including the methicillin-resistant one (MRSA), complete resistance appears simultaneously to erythromycin, azithromycin, the remaining macrolides and the lincosamides. That is why the leaflet separately requires that official guidance on the use of antibacterial agents be taken into account.
Indications
Three of the listed indications carry the caveat «properly diagnosed» in the leaflet: acute bacterial sinusitis, acute bacterial otitis media and exacerbation of chronic bronchitis. The caveat is not a formality — in precisely these conditions the cause often turns out to be non-bacterial, and then the antibiotic helps with nothing except the growth of resistance.
The remaining indications are given without reservations: pharyngitis and tonsillitis, mild to moderately severe community-acquired pneumonia, skin and soft tissue infections, and uncomplicated urethritis and cervicitis caused by Chlamydia trachomatis. One condition is common to all seven items: the pathogen must be sensitive to azithromycin. Infected burn wounds do not belong to this set — for them the medicine is not indicated.
Method of use and dosage
The suspension is given once a day. In children from one year of age the dose is calculated by body weight, and the total course amount is the same for upper and lower respiratory tract infections, otitis media and skin and soft tissue infections: 30 mg per kilogram of body weight for the whole course. Only the ways of spreading it out differ. Data on use in children under one year are limited.
- Three-day schedule: 10 mg/kg once a day for three consecutive days — this is the fastest way to reach the 30 mg/kg of the course.
- Five-day schedule: 10 mg/kg on the first day, then 5 mg/kg from the second to the fifth day. The total dose is the same, the daily load is smaller.
- Pharyngitis caused by Streptococcus pyogenes is the exception to the general rule: here a single dose of 10 mg/kg or 20 mg/kg over three days is effective, up to a maximum of 500 mg a day. Even so, the first-choice medicine both in pharyngitis itself and in preventing subsequent acute rheumatic fever remains penicillin.
- In adults and adolescents the course dose is 1500 mg: 500 mg a day for three days, or 500 mg on the first day and 250 mg from the second to the fifth. Uncomplicated urethritis and cervicitis of chlamydial origin are treated differently — 1000 mg as a single dose.
In elderly patients the medicine is dosed the same as in other adults. In mild and moderate renal impairment, when the glomerular filtration rate stays between 10 and 80 ml/min, and also in mild and moderate hepatic impairment, the dose does not need to be changed. For adults azithromycin also exists in other pharmaceutical forms, and the doctor may prefer them to the suspension.
Contraindications
AzitroLek has one formal contraindication: hypersensitivity to azithromycin, to other macrolide antibiotics or to any excipient of the product. A short list is easily read as «suitable for almost everyone», but that is a mistake — part of the direct prohibitions has been moved into the warnings section, and in force they equal contraindications.
Azithromycin is not given in congenital or documented acquired prolongation of the QT interval, together with other substances that prolong that interval (class IA and III antiarrhythmics, cisapride, terfenadine), in electrolyte disturbances — above all hypokalaemia and hypomagnesaemia — and also in clinically significant bradycardia, rhythm disorders and severe heart failure. Severe liver disease likewise rules the medicine out, and it is not used together with ergotamine derivatives because of the theoretical risk of ergotism. A separate restriction concerns the composition of the suspension: it contains sucrose, so it is unsuitable for people with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency.
Special warnings and precautions
Most of the reservations in the leaflet are devoted not to risks but to the place of this medicine among other antibiotics. In pharyngitis and tonsillitis caused by Streptococcus pyogenes and in preventing acute rheumatic fever the first-choice drug remains penicillin; in sinusitis and acute otitis media azithromycin is also often not the first choice; in infected burn wounds it is not indicated at all. Resistance is added to this: in some European countries more than 30% of Streptococcus pneumoniae strains are not sensitive to azithromycin, and the doctor is obliged to take that into account. There is also a limitation of the form itself — the powder for oral suspension is not suitable for severe infections in which a high concentration of the antibiotic in blood must be reached quickly.
The medicine has risks of its own as well. As with erythromycin and other macrolides, rare severe allergic reactions have been described — angioedema and anaphylaxis, in individual cases fatal; some of them ran in waves, with symptoms returning, and required long observation and treatment. Any diarrhoea that begins after the first doses calls for pseudomembranous colitis to be ruled out. As with every antibiotic, it is worth watching for signs of superinfection with resistant organisms, including fungal ones. With macrolides, prolongation of cardiac repolarisation and of the QT interval has been observed, with a risk of arrhythmias and torsade de pointes tachycardia, and in predisposed people such an effect of azithromycin cannot be completely excluded. Since the medicine is processed by the liver and excreted with bile, it is not used in severe liver disease, and if severe impairment of liver function appears, treatment is stopped; with a glomerular filtration rate below 10 ml/min caution is needed because overall exposure to the drug may increase. Neurological and psychiatric disorders are another reason for caution.
Drug interactions
Most of the list is taken up by medicines that were tested together with azithromycin without any noticeable effect being found: theophylline, carbamazepine with its active metabolite, methylprednisolone, zidovudine, didanosine, indinavir, terfenadine (including no change in the QT interval), rifabutin, and also cimetidine taken two hours before the antibiotic. Still, that list comes with several reservations: with other macrolides an interaction with theophylline has been described, so signs of a rise in its concentration are monitored; with concomitant rifabutin neutropenia was observed, although a link with the combination itself has not been proved; azithromycin increased the content of phosphorylated zidovudine in blood cells, and the clinical significance of this is unknown.
The second part of the list calls for action. Ergotamine derivatives are not used together with azithromycin. Cisapride is processed by the CYP3A4 enzyme, whose activity macrolides suppress, so concomitant use threatens prolongation of the QT interval, ventricular disturbances and torsade de pointes. Antacids lower the maximum concentration of the antibiotic in blood by 30% without changing total bioavailability, so they are separated in time: azithromycin is taken at least one hour before or two hours after them. With coumarin anticoagulants potentiation of the effect has been described, so prothrombin time is checked more often. Ciclosporin and digoxin require monitoring of blood concentration, and with digoxin it may rise, since macrolides limit its processing in the intestine. Nelfinavir raises the area under the curve of azithromycin by 113% and the maximum concentration by 136%; the dose is not changed then, but adverse reactions are watched more closely. On astemizole, triazolam, midazolam and alfentanil there are no data — caution is exercised with them by analogy with erythromycin, in which potentiation of these medicines' effect was described.
Pregnancy and breastfeeding
No adequate and well-controlled studies have been carried out in pregnant women. In animal experiments azithromycin crossed the placenta and in rats showed no teratogenic effect, but the safety of use during pregnancy has remained unestablished. The leaflet's conclusion is strict: during pregnancy the medicine is not used except in life-threatening cases when no other suitable treatment is possible.
Azithromycin does pass into breast milk, and whether it affects the child is unknown, so breastfeeding is stopped for the duration of treatment. In the child, if the antibiotic arrives with the milk, diarrhoea, fungal infection of the mucous membranes and an allergic reaction are possible, among other things. Milk expressed during treatment and for two days after it ends is discarded; later breastfeeding may be resumed.
Adverse reactions
Most often the medicine affects digestion: nausea, vomiting, diarrhoea, abdominal pain and cramps belong to the common reactions. Uncommonly, very loose stools capable of leading to dehydration, abdominal distension and indigestion occur. Rare reactions of the same group are constipation, discoloration of the tongue and pancreatitis. Separately, discoloration of the teeth and pseudomembranous colitis have been described.
Beyond digestion, dizziness, convulsions, headache, drowsiness, disturbances of smell and taste, allergic reactions with rash and itching, joint pain, loss of appetite and vaginitis are noted uncommonly. Rare ones include paraesthesia, fainting, insomnia and hyperactivity, and among psychiatric disturbances aggressive behaviour, agitation, anxiety, nervousness and a feeling of detachment from oneself; in the elderly delirium is possible. Rare but dangerous reactions are considered to be anaphylaxis with oedema, severe skin reactions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), liver function disorders up to hepatitis and cholestatic jaundice and, in isolated cases, liver necrosis and failure, as well as interstitial nephritis and acute renal failure. With long-term use of high doses, hearing loss including deafness and tinnitus has been described, and where patients could be followed further the disturbance proved transient. From the blood and the heart, thrombocytopenia, haemolytic anaemia, transient mild neutropenia, palpitations and rhythm disorders including ventricular tachycardia, as well as a fall in blood pressure, are rarely possible.
Overdose
The picture of macrolide antibiotic overdose is recognisable: transient hearing loss, severe nausea, vomiting and diarrhoea. With doses above those recommended the same reactions were observed as with usual doses — azithromycin produced no new ones characteristic only of excess.
Help is described briefly: gastric lavage and general supportive treatment. Fluid loss deserves separate attention, because vomiting and loose stools dehydrate a child faster than an adult, so in case of overdose a doctor is needed rather than waiting.
How to get a prescription for AzitroLek online
The dose of this suspension is counted by body weight, and three of the seven indications are marked in the leaflet as «properly diagnosed» — that is, the decision belongs to the doctor even when the illness seems familiar to the parents. That is why the questionnaire needs the child's weight, what exactly hurts and for how many days, and whether a swab or culture was taken. AzitroLek is a prescription medicine, and a prescription at e-zdrowie.com is arranged remotely: you fill in a medical questionnaire, the doctor studies the answers, the electronic prescription code arrives by message, and the medicine can be collected at any Polish pharmacy.
This arrangement has another side too, and saying so honestly is more useful than keeping quiet: if the answers point to a viral infection or to a situation in which penicillin remains the first choice, the doctor will prescribe different treatment or suggest further tests first. For an antibiotic that is a normal outcome of a consultation, not a refusal.
