Dalacin - instructions for use, dose, side effects, contraindications

black ink composition TekPrint^TM SW-9008: shellac 24-27%, ethanol 23-26%, isopropanol 1-3%, butanol 1-3%, propylene glycol 3-7%. ammonia solution concentrated 1-2%, iron oxide black 24-28%, potassium hydroxide 0.05-1%, water purified 15-18%.

Capsules 300 mg

Active substance: clindamycin (in the form of clindamycin hydrochloride) 300 mg;

Excipients: lactose monohydrate q.s. up to 650 mg, magnesium stearate 6 mg, corn starch 32 mg, talc 3 mg;

gelatin capsule composition: gelatin q.s. up to 96 mg, titanium dioxide 1.92 mg;

black ink composition TekPrint^TMSW-9008: shellac 24-27%, ethanol 23-26%, isopronanol 1-3%, butanol 1-3%, propylene glycol 3-7%, ammonia solution concentrated 1-2%, iron oxide black 24-28%, potassium hydroxide 0, 05-1%, purified water 15-18%.

Description:

Capsules 150 mg

Hard gelatin capsules No. 1 with a lid and a white body containing white powder; on the cover the inscription with black ink "Pfizer", on the body -"Clin 150“.

Capsules 300 mg

Hard gelatin capsules No. 0 with a lid and a white body containing white powder; on the cover the inscription with black ink "Pfizer", On the body -"Clin 300”.

Pharmacotherapeutic group:Antibiotic-Lincosamide

ATX: & nbsp

J.01.F.F.01 Clindamycin

Pharmacodynamics:

Pharmacodynamics

Clindamycin is a semisynthetic antibiotic-lincosamide, formed from lincomycin upon substitution of 7- (R) -hydroxy group by 7- (S) -chlorine, active against aerobic Gram-positive microorganisms and a wide range of anaerobic bacteria. Most of the graphogenic aerobic bacteria, including Enterobacteriaceae, are resistant to clindamycin.

Clindamycin - binds to 50S subunit of the ribosome and inhibits protein synthesis in bacterial cells, disrupting the extension of the protein chain. Clindamycin is able to inhibit the binding process of aminoacyl t-RNA and the translocation reaction that occurs after the attachment of the amino acid molecule to the ribosome.

Depending on the sensitivity of the microorganism and the concentration of the drug clindamycin can act bacteriostatically (predominantly) or bactericidal (in high concentrations).

The mechanism of resistance

Between lincomycin and clindamycin, there is complete cross-resistance. Resistance of staphylococci and streptococci is most often due to methylation of specific nucleotides in 23S RNA in 50S subunit of the ribosome, which can determine the cross-resistance to macrolides and streptograms B (phenotype MLSB). Strains of microorganisms resistant to macrolides should be tested for inducible resistance to lincomycin / clindamycin using D-test.

Methicillin-sensitive strains Staphylococcus aureus are generally sensitive to clindamycin. Clindamycin has a significant negative effect on many strains of methicillin-resistant staphylococci (MRSA). Nevertheless, the occurrence of a large number of clindamycin-resistant MRSA-stamps excludes the use of clindamycin against infections caused by these microorganisms without a sensitivity test. Some erythromycin-resistant strains of staphylococci in vitro quickly develop resistance to clindamycin.

The following microorganisms usually resistant to clindamycin:

Aerobic Gram-negative microorganisms:

Enterococcus faecalis;

Nocardia spp .;

Neisseria meningitidis;

Strains Haemophilus influenza (in those areas where resistance to antibiotics is observed frequently).

Checkpoints EUCAST for clindamycin (from 2014)

Pathogen	Sensitive	Resistant
Staphylococcus spp.	≤ 0.25 mg / l	> 0.5 mg / l
Streptococcus group A, B. C, G	≤ 0.5 mg / l	> 0.5 mg / l
Streptococcus pneumoniae	≤ 0.5 mg / l	> 0.5 mg / l
Gram-positive anaerobes (with the exception of Clostridium difficile)	≤ 4 mg / l	> 4 mg / l
Gram-negative anaerobes	≤ 4 mg / l	> 4 mg / l

The predominance of acquired resistance

The predominance of acquired resistance may vary depending on the geographical location and time for individual species, so information about resistance in a particular area is highly desirable, especially when treating severe infections.If necessary, consult a specialist if the prevalence of acquired resistance is so widespread that the use of the drug for at least some types of infections is in doubt. Especially with severe infections or lack of success of therapy, microbiological diagnostics with pathogen verification and an assessment of its sensitivity to lincomycin / clindamycin are recommended.

The following information is available on the sensitivity of microorganisms to clindamycin, based on studies conducted in Europe:

Typically, sensitive microorganisms

Aerobic Gram-positive microorganisms

Actinomyces israelii^a

Staphylococcus aureus (methicillin-sensitive)

Streptococcus agalactiae

Group streptococci Viridans

Anaerobic microorganisms

Bacteroides spp. (with the exception of V. fragilis)

Fusobacterium spp.

Peptococcus spp.

Prevotella spp.

Veillonella spp.

Other microorganisms

Chlamydia trachomatis

Chlamydophila pneumoniae

Gardnerella vaginalis

Mycoplasma hominis

Microorganisms for which development of acquired resistance is possible

Aerobic Gram-positive microorganisms

Staphylococcus aureus (methicillin-resistant)

Staphylococcus epidermidis

Staphylococcus haemolyticus

Staphylococcus hominis

Streptococcus pneumonia

Aerobic gram-negative microorganisms

Moraxella catarrhalis^a

Anaerobic microorganisms

Bacteroides fragilis

Clostridium perfringens

Peptostreptococcus spp.

Propionibacterium spp.

Advantageously, resistant microorganisms

Aerobic Gram-positive microorganisms

Enterococcus spp.

Listeria monocytogenes

Aerobic gram-negative microorganisms

Escherichia coli

Klebsiella spp.

Neisseria gonorrhoeae

Pseudomonas aeruginosa

Anaerobic microorganisms

Clostridium difficile

Other microorganisms

Mycoplasma pneumoniae

Ureaplasma urealyticum

Clindamycin can also be used to treat pneumonia caused by Pneumocystis jirovecii (formerly Pneumocystis carinii) in combination with a primaquine and malaria caused by Plasmodium falciparum (in combination with quinine).

Pharmacokinetics:

Suction

After oral reception is a rapid and almost complete (90%) absorption of clindamycin. In adults, after taking clindamycin in a dose of 150 mg, the maximum concentration (C_mOh) clindamycin in blood plasma (2.5 μg / ml) is achieved after 45 minutes, after 3 hours the concentration of clindamycin in the blood plasma is 1.5 μg / ml, and after 6 hours - 0.7 μg / ml. Simultaneous reception of clindamycin with food slows down absorption, without changing the concentration of active substance in the plasma. There is a linear relationship between the concentration of clindamycin in blood plasma and the dose taken. Plasma concentrations of clindamycin exceed the minimum inhibitory concentration (MIC) for most sensitive microorganisms for at least 6 hours after taking the drug at the usual recommended doses.

Distribution

40-90% of the administered clindamycin binds in the body to proteins. Clindamycin easily penetrates into most tissues and body fluids. The concentration of clindamycin in bone tissue reaches about 40% (20-75%) of its concentration in the blood plasma. In maternal milk, the concentration of clindamycin is 50-100% of its concentration in the blood plasma, in synovial fluid - 50%, in sputum - 30-75%, in peritoneal fluid - 50%, in fetal blood - 40%, in pus - 30% , in the pleural fluid - 50-90% of the concentration in the blood plasma. Clindamycin does not penetrate through the intact blood-brain barrier (even with inflammation of the meninges, permeability increases insignificantly).

Metabolism

Clindamycin is almost completely metabolized mainly in the liver with the formation of active (N-dimethyl-clindamycin and clindamidine sulfoxide), as well as some inactive metabolites.

Excretion

The half-life of clindamycin in adults averages about 2.4 hours (with severe hepatic or renal insufficiency slightly lengthened to 3-5 hours), age does not affect the pharmacokinetics of clindamycin.

In an unchanged form, about 10% of clindamycin is excreted from the body by the kidneys, and 3.6% through the intestine. The remaining amount is excreted in the form of inactive metabolites, mainly through the intestine. Clindamycin is not excreted in hemodialysis and peritoneal dialysis.

Indications:

Severe infectious and inflammatory diseases caused by microorganisms sensitive to clindamycin:

1. Infections of the upper respiratory tract and ENT organs. including: chronic sinusitis caused by anaerobic bacteria, otitis media (with the simultaneous use of antibacterial drugs active against aerobic gram-negative microorganisms), recurrent pharyngotongsillitis.

2. Scarlet fever.

3. Infections of the lower respiratory tract, including: bronchitis, pneumonia, pleural empyema and lung abscess.

4. Infections of the skin and soft tissues, including: acne, furunculosis, cellulitis (phlegmon), impetigo, abscesses, infected wounds, erysipelas.

5. Infectious diseases of bones and joints, including: osteomyelitis and septic arthritis.

6. Inflammatory gynecological diseases of the pelvic organs (endometritis, salpingitis, abscesses of the fallopian coarse and ovaries) and pelvioperitonitis (under condition of simultaneous use of antibacterial drugs active against aerobic gram-negative microorganisms).

7. Infections of the cervix caused by Chlamydia trachomatis.

8. Intra-abdominal infections, including: peritonitis and abscesses of the abdominal cavity (with the simultaneous use of antibacterial drugs active against aerobic gram-negative microorganisms).

9. Infections of the oral cavity, including: periodontal abscess and periodontitis.

10. Toxoplasmosis encephalitis in patients with AIDS (in combination with pyrimethamine) with intolerance to standard therapy.

11. Pneumonia caused by Pneumocystis jiroveci (formerly Pneumocystis carinii), in patients with AIDS (in combination with primaquine) with intolerance or resistance to standard therapy.

12. Malaria caused by Plasmodium falciparum, including those with multiple drug resistance (in combination with quinine).

13. Prophylaxis of endocarditis in patients with hypersensitivity to penicillins.

Sensitivity of antibiotics in vitro varies depending on the geographic region and over time, therefore, when choosing antibacterial therapy, local resistance information should be taken into account.

Contraindications:

Hypersensitivity to clindamycin, lincomycin or any component of the drug.

Use in children under 12 years is not recommended in view of the impossibility of adequate dose selection when using the drug in this dosage form (capsule).

Patients with rare hereditary diseases such as lactose intolerance, lactase deficiency or glucose-lactose malabsorption should not take the drug.

Carefully:

Gastrointestinal diseases (in the anamnesis), especially colitis, myasthenia gravis (clindamycin may violate neuromuscular transmission), severe hepatic and / or renal insufficiency.

Caution should be exercised while using Dalacin® with peripheral muscle relaxants. Do not use clindamycin with erythromycin or chloramphenicol (see section "Interaction with other medicinal products").

Pregnancy and lactation:

In animal studies, when clindamycin was administered subcutaneously or inside the effect on fertility, as well as any adverse effects on the fetus, it was not found, except for cases of taking the drug in toxic doses. Clindamycin penetrates the placenta.After the administration of several doses of the drug, the concentration in the amniotic fluid was approximately 30% of the concentration in the mother's blood. In clinical studies with systemic administration of the drug to women during the II and III trimester of pregnancy, there was no increase in the frequency of congenital abnormalities of the fetus. Studies of the use of the drug in women during the first trimester of pregnancy have not been conducted.

Clindamycin should not be used in the first trimester of pregnancy, in II and III trimesters it is used only if the prospective benefit to the mother exceeds the potential risk to the fetus.

Clindamycin is found in breast milk in a concentration of 0.7-3.8 μg / ml. If necessary, the appointment in the lactation period should stop breastfeeding.

Dosing and Administration:

Adults and children over 12 years of age:

600-1800 mg / day orally in 2, 3 or 4 doses (equal doses).

To avoid irritation of the esophageal mucosa, the capsules should be taken with a full glass of water.

If the calculated dose is one dose lower than the clindamycin in the capsule or if swallowing is present, parenteral administration of the drug should be recommended.

Infections caused by beta-hemolytic streptococcus: 300 mg twice a day, treatment should be continued for at least 10 days.

Infectious-inflammatory diseases of the pelvic organs: 900 mg clindamycin iv every 8 h + iv antibacterial agent active against aerobic gram-negative microorganisms (for example, gentamicin at a dose of 2 mg / kg followed by administration of 1.5 mg / kg every 8 hours for patients with normal renal function), for at least 4 days, and after the onset of improvement in the patient - for at least 48 hours. Next shift to clindamycin inside of 450 - 600 mg every 6 hours daily. The full course of therapy is 10-14 days.

Infections of the cervix caused by Chlamydia trachomatis: 450 mg orally 4 times daily for 10-14 days.

Toxoplasmosis encephalitis in patients with AIDS: in patients with intolerance to standard therapy clindamycin apply in combination with pyrimethamine according to the following scheme: 600-1200 mg orally every 6 hours for 2 weeks, then 300-600 mg orally every 6 hours. Pyrimethamine appoint a dose of 25-75 mg orally every day. Usually the course of therapy is 8-10 weeks. When using higher doses of pyrimethamine, folic acid should be prescribed at a dose of 10-20 mg / day.

Pneumonia caused by Pneumocystis iiroveci, in patients with AIDS: 300-450 mg orally every 6 hours for 21 days and primaquine 15-30 mg orally once a day for 21 days.

Malaria:

- uncomplicated malaria / R. falciparum:

Adults:

Quinine sulfate: 650 mg orally three times a day for 3 or 7 days and clindamycin: a dose of 20 mg / kg / day inward, divided into three doses per day for 7 days.

Children:

Quinine sulfate: 10 mg / kg orally three times a day for 3 or 7 days and clindamycin: a dose of 20 mg / kg / day inwards, divided into three doses per day for 7 days.

Severe form of malaria:

Adults:

Quinidine gluconate: a saturating dose of 10 mg / kg intravenously for 1-2 hours, followed by 0.02 mg / kg / min, continued infusion for at least 24 hours (see quinidine application instructions for alternatives). If the concentration of parasites is less than 1% and the patient is able to take the medication internally, the treatment should be completed with quinine in the oral dosage form indicated above together with clindamycin: a dose of 20 mg / kg / day inwards divided into three doses per day for 7 days. If the patient is unable to take the medication internally, a saturating dose of clindamycin 10 mg / kg intravenously and then 5 mg / kg intravenously every 8 hours should be administered.Avoid the rapid administration of the drug intravenously. It is necessary to switch to taking the drug inside (according to the recommended dosage recommendations) as soon as the patient is able to take the drug inside. The course of treatment is 7 days.

Children from 12 to 18 years:

Quinidine gluconate: the same recommendations for dosing and administration regimen, as for adults, described above together with clindamycin: a dose of 20 mg / kg / day inwards, divided into three doses per day for 7 days. If the patient is unable to take the medication internally, a saturating dose of clindamycin 10 mg / kg intravenously and then 5 mg / kg intravenously every 8 hours should be administered. Avoid the rapid administration of the drug intravenously. It is necessary to switch to taking the drug inside (according to the recommended dosage recommendations) as soon as the patient is able to take the drug inside. The course of treatment is 7 days.

Prophylaxis of endocarditis in patients with hypersensitivity to penicillins: 600 mg orally for adults and 20 mg / kg for children 1 hour before a minor surgical or dental intervention or any other procedure involving a risk of endocarditis.

Elderly patients: with normal (for a given age), liver function and kidney correction is not required.

Patients with impaired renal and hepatic function: dose adjustment is not required, since clindamycin practically does not accumulate in the body, if the drug is taken at an interval of 8 hours.

Side effects:

Criteria for frequency estimation: very frequent ≥ 10%; frequent ≥1% and <10%; infrequent ≥ 0.1% and <1%; rare ≥ 0.01% and <0.1%, very rare <0.01%. frequency is unknown - can not be determined from available data.

System-organ class	Frequent ≥ 1/100 to < 1/10	Infrequent ≥ 1/1000 to < 1/100	Rare ≥1 / 1000 0 to <1/1000	Very rare <0,01%	Frequency unknown - can not be determined from available data
Infectious and parasitic diseases	Pseudomembranous colitis * (see section "Special instructions")				Vaginal infection *
Violations from the blood and lymphatic system	Eosinophilia				Agranulocytosis , neutropenia , leukopenia , thrombocytopenia
Immune system disorders				anaphylactic shock*	Anaphylactoid reactions , anaphylactic reaction , hypersensitivity *.
Disturbances from the nervous system		Perversion taste
Violations from sides of the heart		Stopping breathing and cardiac activity (see section "Method of administration and dose")
Violation of the sides of blood vessels		Reduction of blood pressure
Violations from side of the gastrointestinal tract	Diarrhea, abdominal pain	Nausea, vomiting		Colitis	Ulcer of esophagus , esophagitis
Disturbances from the liver and bile ducts	Dysfunction of the liver				Jaundice*
Disturbances from the skin and subcutaneous tissues	Maculopapular rash	Urticaria, erythema multiforme *, itchy skin			Toxic epidermal necrolysis , Stevens-Johnson syndrome , drug rash with eosinophilia and systemic symptomatology (DRESS syndrome) , exfoliative and vesicle-bullous * dermatitis, generalized corneiform rash of mild and moderate severity, acute generalized exanthematous pustulosis *.

* Adverse reactions were detected during post-marketing use.

There is evidence of the possibility of developing the following side effects when using clindamycin: a violation of neuromuscular transmission, development of superinfection.

Overdose:

Symptoms: in case of an overdose there are no specific symptoms (toxicity of clindamycin is not associated with an increase in the dose).

Treatment: In case of an overdose, symptomatic and supportive treatment should be given. Clindamycin is not excreted in hemodialysis and peritoneal dialysis.

Interaction:

Determined that in vitro antagonism between clindamycin and erythromycin. Since this antagonism can be clinically significant, these drugs should not be taken concomitantly.

When used simultaneously with chloramphenicol there is a mutual weakening of the action due to the fact that chloramphenicol can displace clindamycin from a bound state or prevent its binding to a subunit 50S bacterial ribosomes.

Determined that clindamycin violates neuromuscular transmission and, therefore, can enhance the action of other neuromuscular blockers and muscle relaxants of peripheral action, therefore, the drug should be used with caution in patients receiving preparations of these groups, such as vecuronium bromide, rocuronium bromide, gentamicin, rapakuronium bromide (with magnesium) or pancuronium bromide.

Synergistic effects of other antibiotics in their use with clindamycin on the blockers of neuromuscular conduction are described.In this regard, one should be extremely careful when using antibiotics together with muscle relaxants, since their synergistic effect in joint application can cause deeper and longer relaxation of muscles and can delay recovery.

Antagonists of vitamin K

In patients who received clindamycin in combination with vitamin K antagonists (for example, warfarin, acenocoumarol and fluindione), there was an increase in indicators characterizing the blood coagulation capacity (prothrombin time (PV) and international normalized ratio (INR)) and / or bleeding. In this regard, in patients receiving treatment with vitamin K antagonists, frequent monitoring of the results of coagulation tests should be carried out.

Special instructions:

In order to avoid complications, apply strictly to the doctor's prescription!

There have been reports of cases of severe hypersensitivity reactions, including severe skin reactions, such as rash with eosinophilia and systemic symptoms (DRESSsyndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis in patients receiving clindamycin therapy.If a hypersensitivity reaction or a severe skin reaction develops, clindamycin should be discontinued and appropriate therapy of these complications should be initiated (see "Contraindications" and "Side effects").

In case of infections cervical, called Chlamydia trachomatis, monotherapy clindamycin is effective for complete cure.

Clostridium difficile associated diarrhea is observed against the background of almost all antibacterial drugs, including clindamycin and is manifested from mild forms of diarrhea to severe colitis with fatal outcome. Antibacterial drugs suppress the normal flora of the intestine, which can contribute to increased reproduction of clostridia. Clostridium difficile produces toxins A and B, leading to the development of Clostridium difficile associated diarrhea. Hypertoxin-producing strains Clostridium difficile lead to an increase in morbidity and mortality, since they can be resistant to antibiotic therapy and treatment may require a columnectomy. Sue cases of diarrhea in patients with antibiotic therapy should be considered as suspicious for development Clostridium difficile associated diarrhea. Careful collection of anamnesis is necessary in case of development Clostridium difficile associated diarrhea within 2 months after the appointment of antibacterial drugs. Pseudomembranous colitis can occur both with the use of clindamycin, and 2-3 weeks after discontinuation of treatment; is manifested by diarrhea, leukocytosis, fever, abdominal pain (sometimes accompanied by discharge with mucous masses of blood and mucus). After the diagnosis of pseudomembranous colitis in mild cases, it is sufficient to cancel the treatment and apply ion-exchange resins (colestramine, colestipol), in cases of moderate severity and in severe cases, compensation for loss of fluid, electrolytes and protein is indicated, the appointment of an antibacterial drug effective against Clostridium difficile, for example, vancomycin in a dose of 125-500 mg, or bacitracin in a dose of 25,000 units orally 4 times / day for 7-10 days, or metronidazole 250-500 mg 3 times / day.

Contraindicated use of drugs that inhibit intestinal peristalsis. Clindamycin should be used with caution in patients with a history of gastrointestinal disease, especially colitis.Antibiotic-associated colitis and diarrhea occur more often and in more severe form in weakened patients and / or elderly patients.

When using all antibacterial agents, including clindamycin, excess growth of insensitive microorganisms, especially yeast-like fungi, is possible. With the development of superinfection, appropriate measures should be taken depending on the clinical situation.

Clindamycin should not be prescribed for the treatment of meningitis, since it does not penetrate well through the blood-brain barrier.

When prescribing the drug in high doses, it is necessary to monitor the concentration of clindamycin in the plasma. If treatment is carried out within long period of time, then the liver and kidney function tests should be performed regularly.

In patients with impaired liver and kidney function, dose adjustment is not required, since clindamycin practically does not accumulate in the body if the drug is taken internally at an interval of 8 hours. Patients with severe hepatic and / or renal insufficiency need to monitor the function of the liver ("liver" enzymes) and kidneys.

Effect on the ability to drive transp. cf. and fur:

The effect of taking Dalacin® on the ability to drive vehicles and other complex mechanisms has not been studied.

Form release / dosage:

Capsules, 150 mg and 300 mg.

Packaging:

Primary: 8 or 10 capsules in PVC / aluminum foil blisters.

Secondary: 2 or 10 blisters (16 or 100 capsules) together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years

Do not use after the expiration date indicated on the packaging.

Terms of leave from pharmacies:On prescription

Registration number:П N016212 / 01

Date of registration:04.10.2011 / 24.01.2017

Expiration Date:Unlimited

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

Fareva Amboise France

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp20.04.2017

Illustrated instructions

Instructions

Dalacin® (Dalacin®)