INSTRUCTIONS FOR MEDICAL USE
DESPIRON
Trade name of the drug: Despirone
Active substance (INN): Spiramycin
Dispensing form: coated tablets
Contents per tablet:
Active ingredient: spiramycin 1.5 million IU or 3.0 million IU.
Excipients: Aerosil (colloidal anhydrous silicone dioxide), magnesium stearate, corn starch, polyvinylpolypyrrolidone, croscarmellose sodium, microcrystalline cellulose, titanium dioxide, polyethylene glycol 4000, hypromellose.
Description: White to cream-white, biconvex, round, film-coated tablets.
Pharmacotherapeutic group: Antibiotics (gr. macrolides).
ATX code: J01FA02
Pharmacological properties
Spiramycin belongs to antibiotics of macrolide group. The antibacterial spectrum of spiramycin is as follows:
- Generally susceptible microorganisms: minimum suppressive concentration (MPC) < 1 mg/L. More than 90% of strains are sensitive. Streptococci, methicillin-sensitive staphylococci, enterocococci, Rhodococcus equi, Branhamella catarrhalis, Bordetella pertussis, Helicobacter pylori, Campylobacter jejuni, Legionella, Corynebacterium diphtheriae, Moraxella, Mycoplasma pneumoniae, Coxiella, Chlamydia, Treponema pallidum, Borrelia burgdorferi, Leptospira, Propionibacterium acnes, Actinomyces, Eubacterium, Porphyromonas, Mobiluncus, Mycoplasma hominis, Bacteroides, Peptostreptococcus, Prevotella.
- Moderately susceptible microorganisms: the antibiotic is moderately active in vitro. Positive results may be observed at antibiotic concentrations in the inflammation focus higher than the MAC (see Pharmacokinetics). Neisseria gonorrhoea, Clostridium perfringens, Ureaplasma urealyticum.
- Resistant microorganisms (IPC > 4 mg/L): at least 50% of strains of varieties are resistant.
- Methicillin – resistant staphylococci, Enterobacteriaceae, Pseudomonas, Acinetobacter, Nocardia asteroides, Fusobacterium, Haemophilus , Mycoplasma hominis.
Spiramycin activity against Toxoplasma gondii has been proven in vitro and in vivo. Note: Due to lack of clinical indications, some species of bacteria are not listed in the spectrum.
Spiramycin penetrates and accumulates in phagocytes (neutrophils, monocytes and peritoneal and alveolar macrobacteriophages). In humans, concentrations of the drug within phagocytes are quite high. These properties explain the effects of spiramycin on intracellular bacteria.
Pharmacokinetics
Absorption
Absorption of spiramycin is rapid but not complete. According to studies, food intake reduces absorption by 50% and prolongs the time to reach maximum plasma concentration.
Distribution
After oral administration of 6 million ME of spiramycin, the maximum plasma concentration is about 3.3 µg/ml. The plasma elimination half-life is approximately 8 hours. Spiramycin does not penetrate the cerebrospinal fluid, but diffuses into breast milk. It penetrates the placental barrier (fetal blood concentrations are about 50% of those in maternal serum). Placental tissue concentrations are 5 times higher than the corresponding concentrations in blood serum.
The volume of distribution is about 383 liters.
The drug penetrates well into saliva and tissues (concentrations in the lungs are 20 to 60 µg/g, tonsils are 20 to 80 µg/g, infected sinuses are 75 to 110 µg/g, bones are 5 to 100 µg/g). Ten days after the end of treatment, the concentration of the drug substance in the spleen, liver and kidneys is 5 to 7 µg/g.
Binding to plasma proteins is low (approximately 10%).
Biotransformation
Spiramycin is metabolized in the liver to form active metabolites with an unspecified chemical structure.
Excretion
It is excreted mainly in the bile (concentrations are 15-40 times higher than in serum). Renal excretion of active spiramycin is about 10% of the administered dose.
The elimination half-life after administration of 3 million ME of spiramycin is approximately 8 hours. It may be prolonged in elderly patients. No adjustment of the spiramycin dose is required in patients with impaired renal function.
Pregnant women: individual pharmacokinetic properties of spiramycin in pregnant women and the kinetics of maternal to fetal transfer of spiramycin have not been fully understood.
INDICATIONS FOR USE
The use of this medicine is based on the clinical studies and depending on the ranking of spiramycin among modern antibacterial agents, its antibacterial activity and pharmacokinetic properties.
The drug is recommended for the treatment of infections caused by susceptible microorganisms:
- angina, group A beta-haemolytic streptococcus;
- acute sinusitis;
- acute secondary bronchial infection;
- exacerbation of chronic bronchitis;
- non-serious form of community-acquired pneumonia, proceeding without additional dangerous and pneumococcal symptoms. Macrolides are prescribed when community-acquired pneumonia caused by atypical pathogens is suspected, regardless of the severity of the course of the disease and the presence of additional hazards;
- mild forms of skin infections: impetigo, infected dermatoses, ecthyma, infectious dermato-cellulitis (especially rye), erythrasma;
- Dental infections;
- urinary tract infections that are not gonococcal;
- Chemoprophylaxis of recurrent acute joint rheumatism when β-lactam antibiotics are contraindicated;
- Toxoplasmosis, also in pregnancy;
- Prevention of meningococcal meningitis when rifampicin is contraindicated: the goal is to kill the microorganisms (Neisseria meningitides) in the nasopharynx.
Spiramycin is not used to treat meningococcal meningitis;
Methods of use and dosages:
For adults: 2-3 tablets of 3 million IU (i.e., 6-9 million IU) 2 or 3 times daily.
Maximum daily dose for adults: 9 million IU. No dose adjustment is required for elderly patients.
For children (if body weight is 20 kg or more): 150-300 thousand ME/kg/day divided into 2-3 doses. The maximum dose for children is 300,000 ME/kg/day.
Tablets of 3 million ME are not used in children.
Prevention of meningococcal meningitis: 3 million ME every 12 hours (duration 5 days).
Pregnant women infected with toxoplasmosis: 9 million IU before birth or 3 times after confirmation of the diagnosis of toxoplasmosis in the fetus. Thereafter, concomitant use of perimethamine and sulfadiazine is recommended.
Administration:
Tablets are swallowed whole with water.
Side effects
Gastro-intestinal tract: nausea, vomiting, diarrhea and very rare cases of pseudomembranous colitis (less than 0.01%). Single cases of ulcerative esophagitis and acute colitis have been described. The possibility of acute intestinal mucosal damage in patients with AIDS when using high doses of spiramycin for cryptosporidiosis is also noted (only 2 cases).
Peripheral and central nervous system: transient paresthesias.
Liver: in very rare cases (less than 0.01%) – changes in liver function tests and development of cholestatic hepatitis.
Blood organs: very rare cases (less than 0.01%) of acute hemolysis (see “Caution”) and thrombocytopenia.
Cardiovascular system: possible prolongation of the QT interval on electrocardiogram.
Hypersensitivity reactions: skin rash, urticaria, skin itching.
Very rarely (less than 0.01%) – angioedema, anaphylactic shock.
Contraindications
Hypersensitivity to spiramycin and other components of the drug, lactation period.
Spiramycin is not recommended for patients with glucose-6-phosphate dehydrogenase enzyme deficiency because of possible occurrence of acute hemolysis. The drug should be used with caution in case of bile duct obstruction or liver failure.
Drug interactions
Levodopa: due to inhibition of carbidopa absorption, plasma levels of levodopa may decrease. If spiramycin is concomitantly administered, clinical monitoring and some modification of levodopa dosage is required.
Separate problems in OMN imbalance (international normalization ratios) There have been reported situations where an increase in oral anticoagulant activity has been observed in patients receiving antibiotic therapy.
Explicit infection or inflammation, the patient’s age and general condition are considered risk factors; therefore, it can be difficult to determine the effect on OMN imbalance of infection, and its treatment, antibacterial agents and some groups of antibiotics have a greater effect on OMN imbalance than others. These are mainly: fluoroquinolones, macrolides, cyclins, cotrimaxosol, and other cephalosporins.
Special Indications
It is not recommended for use in children under 6 years of age due to difficulty in swallowing the tablets.
Because of insufficient clinical information when used in patients with renal insufficiency, precautionary measures are required. Since small amounts of the drug are excreted with urine, dosage adjustment is required only for patients with renal insufficiency.
When prescribing to lactating women it is necessary to stop breastfeeding because spiramycin may penetrate into the breast milk.
Spiramycin has no teratogenic effect; therefore, pregnant women can take it without fear. Decrease of risk of toxoplasmosis transmission to fetus during pregnancy is registered from 25% to 8% if used in I trimester, from 54% to 19% – in II trimester, and from 65% to 44% – in III trimester. In patients with liver disease it is necessary to periodically monitor its function during the drug treatment.
Pregnancy and lactation
Pregnancy
If necessary, spiramycin may be prescribed during pregnancy.
According to the results of using the drug during pregnancy, the drug has no phytotoxic effect and does not cause developmental abnormalities.
Lactation period
The drug is excreted with breast milk. There is evidence of gastrointestinal tract dysfunction in newborns. Therefore, breastfeeding is not recommended.
Overdose
The toxic dose of spiramycin is unknown.
Gastrointestinal disorders (nausea, vomiting and diarrhea) may be noted after taking high doses of spiramycin.
In case of overdose it is necessary to measure the QT interval, especially in the presence of other dangerous factors (hypokalemia, congenital prolongation of the QT interval, use of drugs prolonging the QT interval and/or causing ventricular contractions).
There is no specific antidote. Symptomatic therapy is recommended in case of suspected spiramycin overdose.
Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children!
Shelf life
2 years. Do not use after the expiration date.
Conditions of dispensing from pharmacies
Released by a doctor’s prescription.