INSTRUCTIONS FOR MEDICAL USE
Trade name of the drug: Despirone
Active substance (INN): Spiramycin
Form release: granules for preparation of suspension for oral administration.
Each 5 ml of the suspension contains:
active substance: spiramycin – 1.5 million IU (333 mg).
Excipients: crosspovidone, sodium benzoate, xanthan gum, sucrose, sucralose, flavoring (vanilla multicomponent).
Description: almost white or slightly yellowish pellets with a smell of vanillin.
Pharmacotherapeutic group: Antibiotics (gr. macrolides)
ATX code: J01FA02
It is an antibiotic of macrolide group. The mechanism of antibacterial action is caused by inhibition of protein synthesis in a microbial cell at the expense of binding to 50S-subunit of ribosome.
Sensitive microorganisms (MAC<1 mg/l): Gram-positive aerobes – Bacillus cereus, Corynebacterium diphtheriae, Enterococcus spp., Rhodococcus equi, Staphylococcus spp. (methicillin-sensitive and methicillin-resistant strains), Streptococcus B, unclassified Streptococcus, Streptococcus pneumoniae, Streptococcus pyogenes; Gram-negative aerobes – Bordetella pertussis, Branhamella catarrhalis, Campylobacter spp, Legionella spp., Moraxella spp.; anaerobes – Actinomyces spp., Bacteroides spp., Eubacterium spp., Mobiluncus spp., Peptostreptococcus spp., Porphyromonas spp., Prevotella spp, Propionibacterium acnes; different – Borrelia burgdorferi, Chlamydia spp., Coxiella spp., Leptospiria spp., Mycoplasma pneumoniae, Treponema pallidum, Toxoplasma gondii.
Moderately susceptible microorganisms (antibiotic is moderately active in vitro at antibiotic concentrations in the focus of inflammation ≥ 1 mg/L, but < 4 mg/L): Gram-negative aerobes – Neisseria gonorrhoeae; aerobes – Clostridium perfringens; various – Ureaplasma urealyticum.
Resistant microorganisms (MPC>4 mg/l; at least 50% of strains are resistant): Gram-positive aerobes – Corynebacterium jekeium, Nocardia asteroides; Gram-negative aerobes – Acinetobacter spp., Enterobacter spp., Haemophilus spp., Pseudomonas spp.; anaerobes – Fusobacterium spp.; miscellaneous – Mycoplasma hominis.
Absorption of spiramycin is rapid but incomplete, with wide variability (10% to 60%). After an oral dose of 6 million IU, the Cmax of spiramycin in plasma is about 3.3 µg/ml. Absorption is not affected by food intake.
Binding to plasma proteins is low (approximately 10%). Vd about 383 l. The drug penetrates well into saliva and tissues (concentration in lungs is 20-60 µg/g, in tonsils
- 20-80 µg/g, in infected sinuses 75-110 µg/g, in bones 5-100 µg/g). 10 days after the end of treatment, spiramycin concentration in spleen, liver, kidney is 5-7 µg/g.
Penetrates through the placental barrier (fetal blood concentrations are approximately 50% of those in maternal serum). Concentrations in placental tissue are 5 times higher than the corresponding concentrations in blood serum. It is excreted with breast milk. Spiramycin does not penetrate the cerebrospinal fluid.
Metabolism and excretion
Spiramycin is metabolized in the liver to form active metabolites with an unspecified chemical structure.
T1/2 from plasma is about 8 hours. It is mainly excreted in the bile (concentration is 15-40 times higher than in serum). Renal excretion is about 10% of the administered dose. The amount of drug excreted in the intestine (with feces) is very low.
INDICATIONS FOR USE
Infectious-inflammatory diseases caused by microorganisms sensitive to the drug:
- Acute and chronic pharyngitis caused by beta-haemolytic streptococcus A (as an alternative to treatment with beta-lactam antibiotics, especially in case of contraindications to their use);
- acute sinusitis (given the sensitivity of the most common microorganisms that cause this pathology, the use of the drug is indicated if there are contraindications to the use of beta-lactam antibiotics)
- acute and chronic tonsillitis caused by spiramycin-sensitive microorganisms;
- acute bronchitis caused by a bacterial infection that developed after acute viral bronchitis;
- exacerbation of chronic bronchitis;
- community-acquired pneumonia in patients without risk factors for adverse outcome, severe clinical symptoms, and clinical signs of pneumococcal etiology of pneumonia;
- pneumonia caused by atypical pathogens (such as Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp.) or suspected (regardless of severity and presence or absence of risk factors for adverse outcome);
- skin and subcutaneous tissue infections, including impetigo, impetiginosis, ecthyma, infectious dermohypodermitis (especially rye), secondary infectious dermatoses, erythrasma;
- Oral infections (including stomatitis, glossitis);
- Non-nococcal genital infections;
- Toxoplasmosis, including in pregnancy;
- Infections of the musculoskeletal system and connective tissue, including periodontal. Prevention of rheumatism recurrence in patients allergic to beta-lactam antibiotics. Eradication of Neisseria meningitidis from the nasopharynx (when contraindicated to take rifampicin) for prevention (but not treatment) of meningococcal meningitis:
- In patients after treatment and before leaving quarantine;
- in patients who have been in contact with persons who have excreted Neisseria meningitidis with saliva into the environment for 10 days before hospitalization.
Administration and dosages
The drug is taken orally.
Method of suspension preparation: suspension is prepared immediately before use. Pellets are shaken in vial, boiled water cooled to room temperature is added to the mark and mixed to get a homogeneous suspension.
Adults are prescribed 6-9 million IU per day. The daily dose is divided into 2 or 3 doses. The maximum daily dose is 9 million IU.
A daily dose of only 1.5 million IU should be used in children and adolescents aged 6 to 18 years.
In children over 6 years of age the daily dose is from 150,300,000 ME per kg of body weight, which is divided into 2 or 3 doses to 6 to 9 million ME. Maximum daily dose in children is 300,000 ME per kg of body weight, but if a child weighs more than 30 kg, it should not exceed 9 million ME.
For prevention of meningococcal meningitis in adults we use 3 million ME twice a day for 5 days, in children – 75000 ME/kg of body weight twice a day for 5 days. Patients with impaired renal function due to insignificant renal excretion of spiramycin do not require dose adjustment.
The following classification was used to indicate the incidence of adverse reactions: very common (≥10%), common (≥1%, <10); infrequent (≥0.1%, <1%); rare (≥0.01%, <0.1%), very rare, including some reports (<0.01%), the incidence is unknown (according to available data the frequency cannot be determined).
Digestive system: nausea, vomiting, diarrhea; very rare – pseudomembranous colitis (<0.01%); frequency unknown – ulcerative esophagitis, acute colitis, acute intestinal mucosal damage in patients with AIDS while using spiramycin in high doses for cryptosporidiosis (only 2 cases).
Liver and biliary tract: very rare (<0.01%) – deviation of liver function tests from normal values; cholestatic or mixed hepatitis.
Nervous system: very rare (isolated cases) – transient paresthesia.
Blood system: very rare (<0.01%) – acute hemolysis.
Cardiovascular system: very rare – prolongation of QT interval on ECG.
Immune system: skin rash, urticaria, itching, very rare (<0.01%) – angioedema, anaphylactic shock, in some cases – vasculitis, including Schoenlein-Henoch purpura.
Skin and subcutaneous tissue: very rare – acute generalized exanthematous pustulosis.
- lactation period;
- glucose-6-phosphate dehydrogenase deficiency (risk of acute hemolysis);
- Hypersensitivity to the drug components.
Caution is exercised when bile duct obstruction and hepatic insufficiency are prescribed.
Patients with impaired renal function due to low renal excretion of spiramycin a dose change is not required.
Spiramycin inhibits absorption of carbidopa with a decrease in plasma concentrations of levodopa. Clinical monitoring and dose adjustment of levodopa is required when spiramycin is concomitantly administered.
Numerous cases of increased activity of indirect anticoagulants in patients taking antibiotics have been reported. The type of infection or severity of the inflammatory reaction, age, and general condition of the patient are predisposing risk factors. In such circumstances, it is difficult to determine the extent to which the infection itself or its treatment plays a role in MHO changes. However, this effect is observed more frequently with certain groups of antibiotics, in particular with fluoroquinolones, macrolides, cyclines, sulfamethoxazole+trimethoprim combination, some cephalosporins.
During treatment with the drug in patients with liver diseases, liver function should be periodically monitored.
If generalized erythema and pustules with high body temperature occur at the beginning of treatment, acute generalized exanthematous pustulosis should be suspected; if such a reaction occurs, treatment should be stopped, and further use of spiramycin, both in monotherapy and in combination, is contraindicated.
Effect on the ability to drive vehicles and operate machinery
There is no information about the negative effect of the drug on the ability to drive vehicles and engage in other potentially dangerous activities. However, the severity of the patient’s condition should be taken into account, which may affect attention and speed of psychomotor reactions. Therefore, the decision about the possibility of driving a car or engaging in other potentially hazardous activities in a particular patient should be made by the attending physician.
Pregnancy and lactation
The drug may be administered during pregnancy when indicated.
There is a wide experience of using the drug during pregnancy. Risk of transmitting toxoplasmosis to fetus during pregnancy is decreased from 25% to 8% if the drug is used in the first trimester, from 54% to 19% – in the second trimester, and from 65% to 44% – in the third trimester. No teratogenic or fetotoxic effects were observed.
Breast-feeding should be discontinued if the drug is administered during lactation, because penetration of spiramycin into the breast milk is possible.
There are no known cases of spiramycin overdose.
Symptoms: nausea, vomiting, diarrhea are possible. Cases of prolongation of the QT interval, which is resolved on withdrawal of the drug, have been observed in infants receiving high doses of spiramycin or after IV administration of spiramycin in patients predisposed to QT interval prolongation.
Treatment: in case of spiramycin overdose ECG-monitoring is recommended with determination of QT interval duration, especially in the presence of risk factors (hypokalemia, congenital prolongation of the QT interval, simultaneous use of drugs that prolong the QT interval and cause development of ventricular tachycardia of “pirouette” type). There is no specific antidote. Symptomatic therapy is recommended in case of suspected spiramycin overdose.
Form of production
Granules for preparation of suspension 1.5 ml/5 ml 75 ml (vials with or without measuring spoon or cup).
Store in a dry, dark place at a temperature not exceeding 25 ° C. Period of storage of suspension after dilution at a temperature not exceeding 25 ° C for a maximum of 7 days, at 4 ° C for a maximum of 14 days.
Keep out of the reach of children!
2 years. Do not use after the expiration date.
Conditions of dispensing from pharmacies
Released by a doctor’s prescription.