Pharmacological properties of the drug Vilprafen
Pharmacodynamics . Josamycin is a broad-spectrum macrolide antibiotic. Active against gram-positive and gram-negative microorganisms, including obligate anaerobes. The drug is also active against mycoplasmas and chlamydia. Pharmacokinetics After oral administration, the drug is rapidly absorbed into the gastrointestinal tract. The maximum concentration in blood plasma is achieved 1 hour after administration. 45 minutes after taking 1 g of the drug, the average concentration of josamycin in the blood plasma is 2.4 mg/l. Josamycin penetrates well through biological membranes and accumulates in various tissues and organs: pulmonary, lymphatic, skin and soft tissues, tonsils, and organs of the urinary system. Binding to plasma proteins does not exceed 15%. Josamycin is metabolized in the liver and is slowly excreted in bile and in small amounts (≤15%) in urine.
Vilprafen
Vilprafen (INN josamycin) is a macrolide antibiotic. It exhibits bacteriostatic and, in high concentrations, bactericidal action. Effective in the treatment of infections caused by staphylococci (including those producing penicillinase), streptococci, corynebacteria, neisseria, Haemophilus influenzae, bordetella, rickettsia, treponema, mycoplasma, chlamydia, some types of shigella, ureaplasma, clostridia. It has virtually no effect on enterobacteria, therefore it does not introduce an imbalance into the natural microflora of the gastrointestinal tract. Can be used in cases of resistance to erythromycin. Resistance to Vilprafen itself develops less frequently and more slowly than to other macrolides. One of the advantages of the drug is its lipophilicity, which ensures rapid penetration of the active substance in therapeutic concentrations into cells and tissues. When using tablet forms of josamycin, its concentration in white blood cells, epithelial cells, macrophages, phagocytes and monocytes is 20 times higher than in the interstitial space. This property of the drug makes it an ideal means of combating chlamydial infections, because The life cycle of these bacteria takes place inside the cell. Compared to other antibiotics, Vilprafen has a very high cure rate for chlamydia - 97% (azithromycin - 55%, doxycycline - 50%). The wide range of therapeutic effects of Vilprafen allows its use in the treatment of mixed bacterial infections, incl. caused by representatives of anaerobic microflora. The drug is practically devoid of teratogenic and embryotoxic effects, which makes it available to pregnant women and provides effective prevention of chlamydia in the neonatal period.
In addition to infections of the genitourinary tract, Vilprafen is used in the treatment of infections of the ENT organs, respiratory tract, oral cavity, soft tissues, and dermatological infections. After oral administration, it is quickly and completely absorbed from the digestive tract. The presence of food masses in the intestines does not affect the bioavailability of the drug (i.e. it can be taken regardless of meals, which is very convenient). The maximum concentration of the active substance in the blood is observed 1-2 hours after administration. It undergoes metabolic transformations in the liver, and the resulting metabolites have less therapeutic activity than the original substance. It is excreted from the body through the biliary (with bile) and genitourinary (with urine) tract. It has a small number of side effects, mainly from the digestive tract (appetite disturbance, nausea, dyspepsia, abdominal cramps, impaired choleretic function). When prescribing Vilprafen, it is necessary to take into account the possibility of adverse interactions with co-administered medications. Thus, this antibiotic slows down the elimination of the antiallergic drugs astemizole and terfenadine, which can lead to the development of severe ventricular arrhythmias. Vilprafen also potentiates the side effects of theophylline, digoxin, and ergot alkaloids (vasoconstrictor effect). And the other side of the coin: Vilprafen can reduce the effectiveness of penicillin and cephalosporin antibiotics, and in combination with lincomycin, the effectiveness of both drugs decreases. For elderly patients, Vilprafen is prescribed in lower doses. ECG monitoring is mandatory in persons concomitantly taking digoxin.
Use of the drug Vilprafen
The recommended dose for adults and children weighing 40 kg is 1 g (initial); then the drug is prescribed 1–2 g per day (2–4 tablets) in 2–3 doses. In severe cases of the disease, the dose can be increased to 3 g. The recommended dose for children over 5 years old weighing ≤40 kg is 40–50 mg/kg body weight per day, divided into several doses. If precise dosing is not possible, the drug for children is used in the form of a suspension. Take the tablets without chewing with a small amount of liquid between meals. The duration of treatment is determined by the doctor. According to WHO recommendations regarding the use of antibiotics, the duration of treatment for streptococcal infections is at least 10 days.
Pharmacokinetics
After oral administration, josamycin is quickly and completely absorbed from the gastrointestinal tract; food intake does not affect bioavailability. Cmax of josamycin in serum is achieved 1–2 hours after administration. About 15% of josamycin is bound to plasma proteins. Particularly high concentrations of the substance are found in the lungs, tonsils, saliva, sweat and tear fluid. The concentration in sputum is 8–9 times higher than the concentration in plasma. Accumulates in bone tissue. Crosses the placental barrier and is secreted into breast milk. Josamycin is metabolized in the liver to less active metabolites and excreted mainly in bile. Excretion of the drug in urine is less than 20%.
Special instructions for the use of the drug Vilprafen
If pseudomembranous colitis develops, the drug must be discontinued and appropriate therapy prescribed. In patients with impaired liver and biliary tract function, treatment is carried out taking into account the results of laboratory tests (for therapy lasting more than 15 days). During pregnancy and breastfeeding . Despite the current lack of data regarding the embryotoxic effect of josamycin, the use of the drug during pregnancy and lactation is permissible in exceptional cases after assessing the risk/benefit ratio of therapy. Use in children. The drug can be used in children over 5 years of age. For children under 5 years of age, as well as when precise dosing is impossible, the drug is prescribed in the form of a suspension. no negative effects on reaction speed when driving vehicles or operating machinery .
special instructions
In patients with renal failure, treatment should be carried out taking into account the results of appropriate laboratory tests.
The possibility of cross-resistance to various macrolide antibiotics should be taken into account (for example, microorganisms that are resistant to treatment with antibiotics related in chemical structure may also be resistant to josamycin).
If one dose is missed, you must immediately take a dose of the drug. However, if it is time for the next dose, do not take the forgotten dose, but return to your normal treatment regimen. You should not take double the dose. A break in treatment or premature discontinuation of the drug will reduce the likelihood of treatment success.
Drug interactions Vilprafen
Since bacteriostatic antibiotics, such as josamycin and bactericidal antibiotics, can interact with each other, the need for simultaneous use of Vilprafen with these antibiotics must be carefully considered. When used simultaneously with lincomycin, the effectiveness of Vilprafen may be reduced. After simultaneous use of Vilprafen and antihistamines that contain terfenadine or astemizole, a slowdown in the elimination of antihistamines may be observed, which in turn can cause life-threatening cardiac arrhythmias. When using Vilprafen together with ergot alkaloids, the possibility of developing a pronounced vasoconstrictor effect should be taken into account. The simultaneous administration of Vilprafen and cyclosporine may lead to an increase in the level of cyclosporine in the blood plasma, which in turn can cause renal dysfunction. With the simultaneous use of Vilprafen and digoxin, an increase in the level of digoxin in the blood plasma is possible.
Wilprafen®
The use of the following drugs in combination with josamycin is contraindicated due to the potential for serious side effects:
— Ergotamine, dihydroergotamine
The result of the interaction is the risk of severe vasoconstriction (ergotism) with the possible development of limb necrosis (due to inhibition of hepatic metabolism and elimination of ergot alkaloids).
— Cisapride, pimozide
As a result of the interaction, the risk of developing life-threatening arrhythmias, including ventricular tachycardia of the “pirouette” type, increases.
— Ivabradin
As a result of the interaction, the plasma concentration of ivabradine and associated side effects increase (due to inhibition of the hepatic metabolism of ivabradine).
— Colchicine
The interaction results in an increased risk of colchicine side effects, including potentially fatal ones.
The use of the following drugs in combination with josamycin is not recommended:
— Ebastine
Increased risk of life-threatening arrhythmias in patients with congenital long QT syndrome.
— Dopamine receptor agonists (bromocriptine, cabergoline, lisuride, pergolide)
An increase in the concentration of dopamine receptor agonists in the blood plasma with a potential increase in their activity and the appearance of overdose symptoms.
— Triazolam
Several cases of increased side effects of triazolam (conduct disorder).
— Halofantrine
Increased risk of ventricular arrhythmias, including ventricular tachycardia of the “torsades de pointes” type. If possible, josamycin should be discontinued. If it is not possible to cancel concomitant use of drugs, monitoring of the QT interval and ECG is necessary.
— Disopyramide
Increased risk of side effects of disopyramide: severe hypoglycemia, increased duration of the QT interval and life-threatening arrhythmias, including ventricular tachycardia of the “pirouette” type. Monitoring of clinical and laboratory data, as well as regular ECG monitoring, is necessary.
— Tacrolimus
Increased plasma concentrations of tacrolimus and creatinine as a result of inhibition of tacrolimus metabolism in the liver.
— Terfenadine and astemizole
During combined use of josamycin and antihistamines containing terfenadine or astemizole, the risk of developing life-threatening arrhythmias may be increased.
The use of the following drugs together with josamycin requires caution:
— Carbamazepine
It is possible to increase the concentration of carbamazepine in the blood plasma and develop overdose symptoms due to inhibition of its hepatic metabolism. It is recommended to monitor the patient's condition and the concentration of carbamazepine in the blood plasma. A dose reduction of carbamazepine may be required.
— Cyclosporine
Co-administration of josamycin and cyclosporine may cause an increase in plasma levels of cyclosporine and creatinine and increase the risk of nephrotoxicity. Plasma concentrations of cyclosporine and renal function should be regularly monitored. The dose of cyclosporine should be adjusted during co-administration with josamycin, as well as after discontinuation of josamycin.
— Anticoagulants of indirect action
It is possible to enhance the effect of indirect anticoagulants and increase the risk of bleeding.
Frequent monitoring of the international normalized ratio (INR) is necessary. It may be necessary to reduce the dose of indirect anticoagulants during co-administration with josamycin, and also in some cases after discontinuation of josamycin.
— Sildenafil
It is possible to increase the concentration of sildenafil in the blood plasma, increasing the risk of arterial hypotension. If co-administration is necessary, it is recommended to take the lowest dose of sildenafil.
— Theophylline and aminophylline
Caution should be exercised when using josamycin together with theophylline or aminophylline, because there is a risk of increased plasma theophylline concentrations, especially in children.
— Digoxin
When administered together, josamycin and digoxin may increase the level of the latter in the blood plasma.
— Other antibacterial drugs
Since bacteriostatic antibiotics in vitro may reduce the antimicrobial effect of bactericidal antibiotics, their simultaneous use should be avoided. Josamycin should not be used simultaneously with lincosamides due to a possible mutual decrease in effectiveness.
