Kubitsin lyophilisate d / pr-r for intravenous injection. 500 mg vial 1 pc. (daptomycin)

Release form

lyophilisate for preparation of solution for infusion

Indications

Complicated infections of the skin and soft tissues in adults

bacteremia caused by Staphylococcus aureus, including established or suspected infectious endocarditis in adults.

Contraindications

Hypersensitivity to daptomycin or excipients.

Caution:

impaired renal function (Cl creatinine <80 ml / min)

obesity

severe impaired liver function (> 9 on the Child-Pough scale)

patients older than 65 years.

severe renal impairment (creatinine Cl < 30 ml / min) - the drug should be prescribed only in cases where the expected benefits of therapy outweigh the potential risk.

Use during pregnancy and lactation

The use of the drug Kubitsin in pregnant women has not been studied. In experimental studies, daptomycin does not adversely affect the course of pregnancy, embryonic / fetal development, childbirth and postnatal development. Prescribe the drug during pregnancy only in those cases when the expected benefit to the mother outweighs the potential risk to the fetus.

It is not known whether daptomycin with breast milk is excreted in humans. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Special instructions

If you suspect a mixed infection (including gram-negative and / or anaerobic microorganisms), Cubicin must be combined with appropriate antibiotics. Limited experience with the use of daptomycin in complicated infections of the skin and soft tissues caused by Enterococcus faecalis and Enterococcus faecium does not allow to draw conclusions about the clinical effectiveness of the drug Kubitsin. There is no experience with the use of the drug in patients after prosthetic valves. According to clinical studies, the drug Kubitsin is ineffective in patients with pneumonia, with bacteremia in patients with severe endocarditis caused by Staphylococcus aureus.

Treatment failure due to persistence or relapse of infection caused by Staphylococcus aureus was observed in 19/120 (15.8%) patients receiving the drug Kubitsin, 9/53 (16.7%) - vancomycin and 2/62 (3.2%) ) - semisynthetic penicillins. In these patients, including 6 people who received the drug Cubicin, and 1 patient from the vancomycin group, there was an increase in MIC during or after therapy. Most patients with persistent or relapse of the infection process had deeply localized infections and did not receive surgical treatment.

In case of deeply localized infections, in order to achieve a clinical effect, an appropriate surgical intervention should be immediately carried out (including debridement, removal of prostheses, valve prosthetics).

Since the development of antibiotic-associated colitis and pseudomembranous colitis from moderate to severe (life-threatening conditions) was noted with the use of almost all antibacterial drugs, the possibility of developing these adverse events should be taken into account when using the drug Kubitsin and the condition of patients with diarrhea during treatment or soon after its graduation.

Resistance development mechanism. The mechanism for the development of daptomycin resistance has not been established.

Decreased sensitivity to daptomycin, as well as to other antibacterial drugs, has been observed in patients with severe, difficult to treat infections and / or for a long period of time. In a clinical study with the use of the drug Kubitsin in 6 patients with endocarditis and bacteremia, a decrease in sensitivity to daptomycin was observed, which may be the reason for the ineffectiveness of antibiotic therapy. In clinical practice, isolated cases of decreased sensitivity to daptomycin have also been noted. Since data on the structure of antibiotic resistance differ depending on the geographical area and change over time, it is recommended to take into account local information on resistance, especially in the treatment of severe infections. If in doubt about the effectiveness of the drug, at least in relation to certain types of pathogens (taking into account local antibiotic resistance), it is recommended to consult a qualified specialist. With the development of antibiotic resistance to daptomycin (superinfection), appropriate measures must be taken.

CPK and myopathy. Since during clinical trials in patients receiving the drug Kubitsin, an increase in CPK activity ( 5 times higher than the upper limit of normal - 5 VGN) without the development of muscle symptoms was noted more often than when using the comparison drug (1.9 and 0.5% accordingly), the following recommendations must be observed: - blood plasma CPK activity is determined before the start of therapy and during treatment with Kubitsin at regular intervals 1 time per week or more often) in all

patients - since the use of the drug in patients with high CPK ( 5 VGN) may increase further enzyme activity, in this category of patients, it is necessary to control the level of CPK more than 1 time per week

- determination of the level of CPK more often than 1 time per week should be performed in patients with an increased risk of myopathy: severe renal failure (Cl creatinine <30 ml / min), the simultaneous use of the drug Kubitsin with drugs that cause myopathy (including statins, fibrates and cyclosporine)

- prescribe the drug Kubitsin along with drugs that cause myopathy, should only be when the benefit of therapy exceeds the possible risk of

- when using the drug Kubitsin, it is necessary to monitor patients for the timely detection of symptoms that indicate the possible development of myopathy

- with the development of muscle pain, pain when pressed, muscle weakness or seizures during therapy with the drug Kubitsin definition CPK activity is carried out every 2 days. In patients with muscle symptoms of an unknown etiology and increased activity of CPK 5 VGN, treatment with the drug should be discontinued.

Peripheral neuropathy. In case of development of symptoms of peripheral neuropathy, patients should be examined and consideration should be given to stopping treatment with Cubicin.

Renal failure. With the introduction of the drug Kubitsin, there have been isolated cases of the development of renal failure, however, the relationship of this adverse event with the drug has not been established.

In patients with severe renal failure, an increase in plasma concentrations of daptomycin is possible, leading to an increased risk of myopathy. In clinical studies, impaired renal function was more often observed in patients receiving the comparison drug than the drug Kubitsin.

Impact on the ability to drive vehicles and / or work with machinery. The effect of the drug on the ability to drive vehicles and work with mechanisms has not been studied. However, given the safety profile of the drug Kubitsin, a negative effect of the drug on the ability to perform potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions is unlikely.

Composition

Lyophilisate for solution for infusion 1 fl.

daptomycin 350 mg

500 mg

component composition without the amount of

excipients: sodium hydroxide solution zn

Dosage and administration of

IV, in the form of infusion, for at least 30 minutes.

Complicated infections of the skin and soft tissues

The recommended dose for adults is 4 mg / kg once a day for 7-14 days or until the infection disappears. With the development of bacteremia caused by Staphylococcus aureus, 6 mg / kg of the drug is prescribed once a day.

Bacteremia caused by Staphylococcus aureus, including established or suspected infectious endocarditis

The recommended dose for adults is 6 mg / kg 1 time in knocking for 2-6 weeks at the discretion of the attending physician.

Patients with impaired renal function. In patients with Cl creatinine ?30 ml / min, dose adjustment of the drug is not required.

In patients with Cl creatinine <30 ml / min or patients receiving hemodialysis or continuous ambulatory peritoneal dialysis, the interval between injections of the drug Kubitsin should be increased to 48 hours (this correction of the dosage interval has not been studied in clinical studies and is based on pharmacokinetic modeling data )

In patients with end-stage kidney disease, Cubicin should be given on the same day after hemodialysis.

Patients with impaired liver function. In patients with mild to moderate impaired liver function (<8 points on the Child-Pough scale), dose adjustment is not required.

Because in patients with severely impaired liver function (> 9 points on the Child-Pough scale) the effectiveness and safety of daptomycin have not been studied, care should be taken when prescribing the drug Kubitsin in this category of patients.

Patients older than 65 years. Patients older than 65 years with a lack of severe renal impairment, the drug is prescribed with caution in a dose of 4 or 6 mg / kg once a day.

Since the experience of using the drug Kubitsin in patients over 65 years of age is limited, caution must be exercised when using the drug in this category of patients.

Children and adolescents (under 18 years old). Since the effectiveness and safety of the drug Kubitsin in children and adolescents has not been established, the drug is not recommended for use in this category of patients.

Rules for the preparation and administration of a solution of the drug Kubitsin

1. To obtain an iv solution with daptomycin concentration of 50 mg / ml: - 350 mg of lyophilisate should be dissolved in 7.0 ml of 0.9% sodium chloride solution or sterile water for injection

- 500 mg of lyophilisate should be dissolved in 10.0 ml of 0.9% sodium chloride solution or sterile water for injection.

Preparation of a solution of the drug cubicin is carried out under aseptic conditions. The polypropylene “flip off” cap must be removed to detect the central part of the rubber plug. 7 or 10 ml of a 0.9% solution of sodium chloride or sterile water for injection is introduced into the vial through the center of the rubber stopper, directing the needle to the wall of the vial. The bottle must be carefully rotated to ensure complete dissolution of the drug, after which it should be left for 10 minutes. The vial should then be gently shaken for 5 minutes until the desired clear reconstituted solution is obtained. In order to avoid foaming of the drug, the vial should not be shaken vigorously. Complete dissolution of the lyophilisate usually occurs within 15 minutes.

Prior to the administration of the drug Kubitsin, visually check the quality of dissolution of the drug and the color of the solution. The solution of the drug Kubitsin should be from pale yellow to light brown. When the color changes or the appearance of insoluble visible particles, the drug can not be used.

The chemical and physical stability of the dissolved drug in the vial is maintained for 4 hours at temperatures up to 30 ° C for 12 hours at temperatures up to 25 ° C for 48 hours at 2–8 ° C.

2. The resulting solution of the drug Kubitsin should be diluted 50 ml 0, 9% sodium chloride solution and injected intravenously for 30 minutes.

The chemical and physical stability of the diluted solution in infusion bags is maintained for 12 hours at temperatures up to 25 ° C or 24 hours at 2–8 ° C. From a microbiological point of view, a diluted solution of the drug for iv administration should be used immediately after preparation. If the prepared infusion solution is not used immediately, the storage time should not exceed 24 hours at a temperature of 2–8 ° C.

The total Expiration of the daptomycin solution in the vial and the diluted drug solution in the infusion bag should not exceed 12 hours at 25 ° C or 24 hours at 2–8 ° C.

3. After a single injection of the drug Kubitsin, the unused solution of the drug remaining in the vial cannot be reused.

4. After using the product, all materials should be disposed of properly.

Do not mix Cubicin with glucose-containing solutions.

Side effects of

In clinical trials, more than 1,500 people received treatment with Cubicin (for 7-14 days).

The most common adverse reactions were headache, nausea, vomiting, diarrhea, fungal infections, rash, reactions at the injection site, increased activity of CPK and liver enzymes - ALT, ACT and alkaline phosphatase.

During clinical trials, the following adverse events were noted, listed below on organs and systems with an indication of their frequency of occurrence: often (? 1/100, <1/10) sometimes (? 1/1000, <1/100) rarely (? 1 / 10000, <1/1000), very rarely (? 1/10000), incl. individual messages. In each group, adverse events are presented in decreasing order of severity.

Infectious diseases: often - fungal infections, sometimes - urinary tract infections.

From the hemopoietic system: sometimes - thrombocythemia, anemia, eosinophilia.

Disorders of metabolism and nutrition: sometimes - anorexia, hyperglycemia.

Mental disorders: sometimes - anxiety, insomnia.

From the nervous system and sensory organs: often - headache sometimes - dizziness, paresthesia, taste disturbances.

From the cardiovascular system: sometimes - supraventricular tachycardia, extrasystole, flushing of the face, increase or decrease in blood pressure.

From the digestive system: often - nausea, vomiting, diarrhea sometimes - constipation, abdominal pain, dyspepsia, glossitis.

From the liver and biliary tract: sometimes - jaundice.

From the skin and subcutaneous tissue: often - rash sometimes - itching, urticaria.

From the musculoskeletal system: sometimes - myositis, muscle weakness, myalgia, arthralgia.

From the urinary system: sometimes - impaired renal function.

From the reproductive and endocrine system: sometimes - vaginitis.

On the part of the body as a whole, local reactions: often - reactions at the injection site, sometimes - fever, weakness, fatigue, pain.

Change in laboratory results: often - violation of laboratory parameters of liver function (increased activity of ACT, ALT and alkaline phosphatase), increased activity of CPK, sometimes - violation of electrolyte balance, increased plasma levels of creatinine, myoglobin, increased activity of LDH.

When using the drug Kubitsin in clinical practice, the following adverse events were noted: From the immune system: very rarely - hypersensitivity (individual spontaneous reports), including pulmonary eosinophilia, vesicular-bullous rash involving mucous membranes and sensation of swelling of the oropharynx, anaphylaxis, post-infusion reactions, including tachycardia, wheezing, fever, chills, systemic hyperemia, dizziness, fainting, fainting, fainting,

From the musculoskeletal system: very rarely - rhabdomyolysis. In approximately 50% of cases, rhabdomyolysis was observed in patients with preexisting renal failure or with the simultaneous use of the drug Kubitsin with drugs that cause rhabdomyolysis.

Change in laboratory results: in some cases, myopathy, manifested by muscle symptoms and increased activity of CPK, was accompanied by an increase in transaminases. The increased activity of transaminases was probably associated with the effect of the drug on skeletal muscle. In most cases, an increase in the activity of transaminases of 1-3 degrees was observed, disappearing after the cessation of therapy with the drug Kubitsin.

Drug interaction

Daptomycin is not metabolized or is slightly metabolized with the participation of the cytochrome P450 isoenzyme system (CYP450).

Since in vitro studies the drug does not have a clinically significant inducing or inhibitory effect on the CYP450 isoenzyme system (1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4), the development of SUR450-dependent interactions in humans is unlikely.

Experience with the simultaneous use of daptomycin with drugs whose use may be accompanied by myopathy is limited. However, there have been several cases of increased CPK activity and the development of rhabdomyolysis in patients taking the drug Kubitsin along with drugs that cause myopathy. Prescribe the drug Kubitsin along with drugs that cause myopathy, should only be in cases where the benefits of therapy outweigh the possible risk.

When using the Kubitsin pre-drug along with drugs that can cause myopathy, it is necessary to monitor the activity of KFK more than 1 time per week and ensure that patients are monitored in order to detect any symptoms indicating the development of myopathy in a timely manner.

Since excretion of daptomycin occurs mainly by renal filtration, its plasma concentration may increase with the use of drugs that reduce renal filtration (including NSAIDs, including selective COX-2 inhibitors). In addition, with the use of daptomycin with these drugs, the development of pharmacodynamic interaction is possible due to the additive effect on renal function.

Caution is advised to use the drug Kubitsin together with potentially nephrotoxic drugs, providing additional regular monitoring of renal function in all patients (regardless of the initial state of renal function).

In clinical practice, there have been cases of interaction of daptomycin with a specific reagent used in the determination of PV / INR. This interaction led to a pronounced elongation of PV and an increase in MHO. If abnormalities in PV / INR are detected in patients receiving treatment with Kubitsin, the possibility of interaction of daptomycin in vitro with a laboratory reagent should be considered. The probability of errors in the determination of PV or MHO can be minimized if blood sampling is performed at the lowest possible concentration of daptomycin in the blood plasma.

If necessary, the drug can be used (iv) simultaneously with aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine.

Incompatibility. You can not mix the drug Kubitsin with glucose-containing solutions, as well as other drugs, with the exception of the above.

Overdose

Treatment: symptomatic therapy and medical supervision. Daptomycin is slowly removed from the body by hemodialysis (about 15% of the dose taken after 4 hours) or by peritoneal dialysis (about 11% of the dose removed after 48 hours).

Storage Conditions

At 2-8 ° C.

Keep out of the reach and sight of children.

The Expiration of

is 3 years.

active substance

Daptomycin

Prescription terms from

pharmacies Prescription

lekarstvennaja form

Solution for infusion

Possible product names

Kubitsin vial, 500 mg



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