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

Clindamycin is a semisynthetic antibiotic-lincosamide derived from lincomycin upon substitution of 7- (R) -hydroxyl group by 7- (S) -chlor, which is active against aerobic gram-positive microorganisms and a wide spectrum of anaerobic bacteria. Most of the graphogenic aerobic bacteria, including Enterobacteriaceae, are resistant to clindamycin.

Clindamycin binds to the 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. The resistance of staphylococci and streptococci is most often due to methylation of specific nucleotides in 23S RNA in the 50S subunit of the ribosome, which can determine 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 the 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 strains precludes 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).

EUCAST control points 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

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

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 the administration of 600 mg of clindamycin phosphate intramuscularly (in / m) the maximum concentration of clindamycin in the blood serum (9 μg / ml) is achieved 1-3 h from the moment of administration. After intravenous (IV infusion of 300 mg clindamycin for 10 min or 600 mg clindamycin for 20 min, the maximum clindamycin concentration, which is 7 μg / ml and 10 μg / ml, respectively, is achieved by the end of clindamycin administration.The table shows the average maximum concentrations of clindamycin and clindamycin phosphate in the serum after its administration.

Clindamycin phosphate is given to adults every 8-12 hours, children every 6-8 hours, or as a constant IV infusion, which provides a clindamycin concentration in the serum that exceeds the minimum concentration of the drug in vitro, necessary to suppress the most sensitive microorganisms to clindamycin. A constant level of clindamycin in the body is achieved after the administration of the third dose.

Doses in adults (after reaching the equilibrium concentration)	Clindamycin (μg / ml)	Clindamycin phosphate (μg / ml)
IV infusion of 300 mg for 10 minutes every 8 hours	7	15
in / in 600 mg for 20 minutes every 8 hours	10	23
in / in 900 mg for 30 minutes every 12 hours	11	29
in / in 1200 mg for 45 minutes every 12 hours	14	49
in / m 300 mg every 8 hours	6	3
in / m for 600 mg every 12 hours	9	3
Doses in children (first dose) (1)
IV, 5-7 mg / kg body weight for 1 hour	10
in / m 3 - 6 mg / kg body weight	4
in / m at 5 - 7 mg / kg body weight	8

(1) patient data, receiving treatment for an infection

There is a linear relationship between the concentration of clindamycin in the serum and the dose taken.Serum 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 approximately 40% (20-75%) of its serum concentration. In maternal milk, the concentration of clindamycin is 50-100% of its concentration in the blood serum, 50% in synovial fluid, 30-75% in sputum, 50% in peritoneal fluid, 40% in fetal blood, 30% in pus. , in the pleural fluid - 50-90% concentration in the blood serum. Clindamycin not permeates through the intact blood-brain barrier (with inflammation of the meninges, permeability increases insignificantly).

Metabolism

Clindamycin is almost completely metabolized in the liver with formation N-detyl and sulfoxide active metabolites, 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 lengthened to 3-5 hours),age does not affect the pharmacokinetics of clindamycin.

In an unchanged form, about 10% of clindamycin is excreted by the kidneys, and 3.6% by the intestine. The rest of the amount is excreted in the form of inactive metabolites, mainly with bile and feces. Clindamycin is not excreted by 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 tubes and ovaries) and pelvioperitonitis (under the condition of simultaneous use of antibacterial drugs active against aerobic gram-negative microorganisms).

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

8. Septicemia and bacterial endocarditis.

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).

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, children under 3 years (for this dosage form).

Carefully:

Gastrointestinal diseases (in the anamnesis), especially colitis, myasthenia gravis (clindamycin can disrupt neuromuscular transmission), Heavy hepatic and / or renal failure, bronchial asthma.

Caution should be exercised while using Dalazin C^®phosphate with muscle relaxants of peripheral action.

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 about 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 I trimester of pregnancy, in II and III trimester applies only if the intended 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.

Benzyl alcohol can penetrate the placenta (see section "Special instructions").

Dosing and Administration:

Intravenous drip, intramuscularly.

Adults

The usual daily dose, including for the treatment of intra-abdominal infections, inflammatory gynecological diseases of the pelvic organs, as well as other complicated or serious infections, as a rule, under the condition of simultaneous application of antibacterial drugs active against aerobic gram-negative microorganisms: 2400 to 2700 mg of the drug per day, divided into 2, 3 or 4 equal doses.In infections caused by more sensitive pathogens: 1200 - 1800 mg / day, divided into 3 or 4 equal doses.

The maximum daily dose is up to 4800 mg.

Infectious-inflammatory gynecological diseases of the pelvic organs: 900 mg clindamycin iv every 8 h + antibacterial drug 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 for 450-600 mg every 6 hours daily. The full course of therapy is 10-14 days.

Toxoplasmic encephalitis in patients with AIDS: in patients with intolerance to standard therapy clindamycin apply in combination with pyrimethamine according to the following scheme: iv in a dose of 600-1200 mg every 6 hours for 2 pedules, 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 given at a dose of 10-20 mg / day.

Pneumonia caused by Pneumocystis jiroveci (formerly Pneumocystis carinii), in patients with AIDS: 600-900 mg IV every 6 hours or 900 mg IV every 8 hours for 21 days and primaquine 15-30 mg orally once a day for 21 days.

Severe form of malaria

Adults:

Quinidine gluconate: 10 mg / kg as a saturating dose, intravenously for 1-2 hours, then 0.02 mg / kg / min for a prolonged infusion for at least 24 hours (an alternative dosage regimen is provided in the quinidine administration manual). Once the parasite concentration becomes <1% and the patient can take the medications internally, quinine administration should be completed inward at the dose indicated above, in combination with clindamycin: 20 mg / kg / day inwards, divided into 3 equal doses, for 7 days .

In case the patient is unable to take the drugs inside, you should enter clindamycin in / in the drip in a saturating dose of 10 mg / kg, followed by the administration of the drug at a dose of 5 mg / kg IV drip every 8 hours. Quick introduction of the drug should be avoided. Once the patient can take the drugs inside, go to the tablet form. The duration of the course of treatment is 7 days.

Children:

Gluconate of quinidine: the same dosage scheme as described above for adults in combination with clindamycin: 20 mg / kg / day inwards, divided into 3 equal doses, for 7 days.If the patient is unable to take the drugs inside, you should enter clindamycin in / in the drip in a saturating dose of 10 mg / kg, followed by the administration of the drug at a dose of 5 mg / kg IV drip every 8 hours. Quick introduction of the drug should be avoided. Once the patient can take the drugs inside, go to the tablet form.

Children from 3 to 18 years old

20-40 mg / kg body weight / day, divided into 3 or 4 equal doses.

Elderly patients

With normal (for a given age), liver and kidney function is not required.

Patients with impaired renal and hepatic function

Dose correction is not required, since clindamycin practically does not accumulate in the body, if the drug is administered at an interval of 8 hours.

Mode of application

1. Intravenously drip.

Dalacin C® phosphate for intravenous drip administration should be previously diluted. Do not administer bolus!

The concentration of clindamycin in the solution for infusion should not exceed 18 mg / ml.

The infusion rate should not exceed 30 mg / min (see the "Side effect" section).

The following infusion rates are usually used:

Dose	Volume of solvent *	Time
300 mg	50 ml	10 min
600 mg	50 ml	20 minutes
900 mg	50-100 ml	30 min
1200 mg	100 ml	40 min

* Solvent - 0.9% solution of sodium chloride or 5% solution of dextrose. Examine the finished infusion solution to make sure there are no suspended particles or discoloration.

Introduction of more than 1200 mg per infusion of 1 hour is not recommended.

2. Intramuscular.

Intramuscular injection at one time more than 600 mg is not recommended. Dalacin C^®phosphate should not be diluted before intramuscular injection.

Side effects:

System-Organ Class	Frequent ≥ 1/100 to < 1/10	Infrequent ≥1/1000 to < 1/100	Rare ≥1 / 10000 to <1/1000	Very rare < 1/10000	Frequency unknown - can not be determined from available data
Infectious and parasitic diseases	Pseudomembranous colitis * (see section "Special instructions")				Vaginal infections *
Violations of 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
Heart Disease		Stopping breathing and cardiac activity (see section "Method of administration and dose") **
Vascular disorders	Thrombophlebitis (reduce the incidence of this phenomenon can be by injecting the drug deeply intramuscularly, and, if possible, avoiding the use of permanent intravenous catheters)	Decrease blood pressure **
Violations from side of the gastrointestinal tract	Abdominal pain, diarrhea	Nausea, vomiting		Colitis	Ulcer of esophagus , esophagitis
Disorders 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 coret-like rash of mild and moderate severity, acute generalized exanthematous pustulosis *.
Are common disorders and disorders at the site of administration		When Intravenous or intramuscular administration of the drug may exhibit soreness and abscess formation in placeinjections (reduce the incidence of these phenomena can be by administering the drug intramuscularly, and, if possible, avoiding the use of permanent intravenous catheters)			Local irritation *, (to reduce the incidence of these phenomena can be by introducing the drug deeply intramuscularly, and, if possible, avoiding the use of permanent intravenous catheters)

* Adverse reactions were detected during post-marketing application

** With too rapid IV injection of the drug, rare cases are noted

In the reference literature, there are data on the possible development of the following side effects when using clindamycin: a violation of neuromuscular transmission, development of superinfection.

Overdose:

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

Treatment: In case of an overdose, symptomatic and supporting treatment. 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.

With the simultaneous use of clindamycin 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.

It was found that with iv introduction clindamycin violates neuromuscular transmission and, therefore, may enhance the action of other neuromuscular blockers or 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 effect is described other antibiotics when they are used with clindamycin for blockers of neuromuscular conduction. In this regard, one should be extremely careful when using antibiotics together with muscle relaxants, since their synergistic action when combined can cause deeper and longer relaxation of the muscles and mayto 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.

Clindamycin is pharmaceutically incompatible with: ampicillin, phenytoin, barbiturates, aminophyllium, calcium gluconate, magnesium sulfate, ceftriaxone and ciprofloxacin.

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" sections).

The product contains benzyl alcohol. There are reports that benzyl alcohol causes the development of "suffocation syndrome" (Gasping Syndrome - violations of the respiratory system, manifested in the form of suffocation) with a fatal outcome in children. Despite the fact that therapeutic doses of the drug usually contain a dose of benzyl alcohol is significantly lower than the dose at which this complication was observed, the minimum amount of benzyl alcohol, having a toxic effect, is unknown. The degree of toxicity of benzyl alcohol depends on the amount of injected drug and the ability of the liver and kidneys to detoxify chemical compounds. In premature infants and children with low birth weight, the risk of toxic damage is higher.

The amount of benzyl alcohol per 1 ml of the drug solution is 9 mg.

Clostridium difficile associated diarrhea is observed against the background of almost all antibacterial drugs, including clindamycin and manifests itself from mild forms of diarrhea to severe colitis with a 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. All 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.

Drugs that reduce gastrointestinal motility should not be prescribed simultaneously with clindamycin.

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 using the drug in high doses, it is necessary to monitor the concentration of clindamycin in the blood 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 administered at an interval of 8 hours. Patients with severe hepatic and / or liver failure should use the drug with caution and monitor liver function (liver enzymes) and kidneys.

The drug should not be administered intravenously in undiluted form and simultaneously. Infusion should be carried out for at least 10-60 minutes (see section "Method of administration and dose").

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

The effect of the drug on the ability to drive vehicles and control other mechanisms that require increased concentration and speed of the psychomotor reaction has not been studied.

Form release / dosage:

Solution for intravenous and intramuscular injection, 150 mg / ml.

Packaging:

By 2 ml, 4 ml and 6 ml into ampoules of colorless Class I glass (Heb.Pharm.).

1 or 10 ampoules placed in a plastic pallet, with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N013455 / 01

Date of registration:04.12.2008

Expiration Date:Unlimited

Date of cancellation:2017-08-21

The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium

Manufacturer: & nbsp

PFIZER MFG. BELGIUM, N.V. Belgium

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp21.08.2017

Illustrated instructions

Instructions

Dalacin® TS Phosphate (Dalacin® C phosphate)