Tygacil powder for preparation of solution for infusions 50 mg bottle No. 10

Instructions Tygacil powder for preparation of solution for infusions 50 mg bottle No. 10

Composition

active ingredient: tigecycline;

1 vial contains 50 mg of tigecycline;

Excipients: lactose monohydrate; diluted hydrochloric acid; sodium hydroxide.

Dosage form

Powder for solution for infusion.

Main physicochemical properties: lyophilisate in the form of a sticky mass or orange powder.

Pharmacotherapeutic group

Antibacterials for systemic use, tetracyclines. ATX code J01A A12.

Pharmacological properties

Pharmacodynamics.

Mechanism of action.

Tigecycline, a glycylcycline antibiotic, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and by blocking the entry of amino-acyl-tRNA molecules into the A site of the ribosome. This prevents the incorporation of amino acid residues into growing peptide chains.

Tigecycline is generally considered to be bacteriostatic in nature. Tigecycline was tested against Enterococcus spp., Staphylococcus aureus, and Escherichia coli at concentrations 4 times the minimum inhibitory concentration (MIC) and showed a 2-log reduction in colony count.

Mechanism of resistance.

Tigecycline is able to overcome the 2 main mechanisms of tetracycline resistance: ribosomal protection and active efflux. For Enterobacterales, cross-resistance exists between tigecycline and minocycline-resistant isolates due to efflux pumps that confer multidrug resistance. There is no target-based cross-resistance between tigecycline and most classes of antibiotics. Tigecycline is susceptible to chromosomally encoded efflux pumps that confer multidrug resistance, members of the Proteeae and Pseudomonas aeruginosa. Proteeae (Proteus spp., Providencia spp., and Morganella spp.) are generally less susceptible to tigecycline than other members of the Enterobacterales. Reduced susceptibility in both groups is associated with overexpression of the nonspecific efflux pump AcrAB, which confers multidrug resistance. Reduced susceptibility of Acinetobacter baumannii is associated with overexpression of the efflux pump AdeABC.

Antibacterial activity in combination with other antibacterial agents

In vitro studies have rarely shown antagonism between tigecycline and other commonly used classes of antibiotics.

Boundary points.

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has established the following MIC breakpoints:

(†) For other Enterobacterales, the activity of tigecycline varied from negligible for Proteus spp., Morganella morganii, and Providencia to significant for other species.

Clinical efficacy has been demonstrated against anaerobic bacteria in polymicrobial intra-abdominal infections, but there is no correlation between MIC values, pharmacokinetic/pharmacodynamic data, and clinical outcomes. Therefore, no breakpoint information for susceptibility is provided. It should be noted that the MIC range for organisms of the genera Bacteroides and Clostridium is wide, which may include values exceeding 2 mg/L tigecycline.

There are limited data on the clinical efficacy of tigecycline against enterococci. However, clinical studies have demonstrated that polymicrobial intra-abdominal infections are treatable with tigecycline.

Sensitivity.

The frequency of acquired resistance may vary depending on the location and period of sampling of the microorganisms tested; local information on resistance is also desirable, especially when treating severe infections. Expert advice should be sought when local acquired resistance has reached a level that makes the benefit of the drug in at least some types of infections questionable.

Pathogenic microorganisms.

Mostly sensitive species.

Gram-positive aerobes:

Enterococcus spp.†

Staphylococcus aureus*

Staphylococcus epidermidis

Staphylococcus haemolyticus

Streptococcus agalactiae*

Streptococcus anginosus group* (includes S. anginosus, S. intermedius, S. constellatus)

Streptococcus pyogenes*

Viridans group streptococci

Gram-negative aerobes:

Citrobacter freundii*

Citrobacter koseri

Escherichia coli*

Anaerobes:

Clostridium perfringens†

Peptostreptococcus spp.†

Prevotella spp.

Species for which acquired resistance may be a problem

Gram-negative aerobes

Acinetobacter baumannii

Burkholderia cepacia

Enterobacter cloacae*

Klebsiella aerogenes

Klebsiella oxytoca*

Klebsiella pneumoniae*

Stenotrophonas maltophilia

Anaerobes:

Bacteroides fragilis group†

Naturally resistant species.

Gram-negative aerobes

Morganella morganii

Proteus spp.

Providencia spp.

Serratia marcescens

Pseudomonas aeruginosa

* Species for which satisfactory activity was shown in clinical studies are noted.

† See “Border points” above.

In a randomized, placebo- and active-controlled, four-stage crossover QTc study in 46 healthy volunteers, no significant effect on the QTc interval was observed with a single dose of tigecycline 50 mg or 200 mg intravenously.

Children.

Tigecycline (0.75, 1, or 1.25 mg/kg) was administered in an open-label, multiple-escalation study in 39 children aged 8 to 11 years with complicated intra-abdominal infections or complicated skin and soft tissue infections. All patients received tigecycline intravenously for a minimum of 3 to a maximum of 14 consecutive days with the option to switch to oral antibiotics on day 4 or later.

Clinical response was assessed between days 10 and 21 after the last dose. Summary results for clinical response in the modified intent-to-treat (mITT) population are presented in Table 1.

Table 1.

Clinical recovery, mITT population.

The above efficacy data should be considered with caution, as concomitant antibiotics were allowed in this study; in addition, the small number of patients should be taken into account.

Pharmacokinetics.

Absorption.

The bioavailability of tigecycline is 100% because it is administered intravenously.

Distribution.

In vitro plasma protein binding of tigecycline was approximately 71-89% at concentrations observed in clinical studies (0.1 to 1.0 μg/mL). Pharmacokinetic studies in animals and humans have demonstrated that tigecycline is rapidly distributed into tissues.

Following single or multiple dose administration of 14C-tigecycline to rats, radioactivity was well distributed to most tissues; the highest amounts were found in bone marrow, salivary glands, thyroid, spleen, and kidney. In humans, the steady-state volume of distribution of tigecycline averages 500–700 L (7–9 L/kg), indicating active distribution of tigecycline outside of plasma and accumulation in tissues.

There are no data on the ability of tigecycline to cross the blood-brain barrier in humans.

In clinical pharmacology studies using a therapeutic dose (100 mg, then 50 mg every 12 hours), the steady-state serum Cmax of tigecycline was 866 ± 233 ng/mL after a 30-minute infusion and 634 ± 97 ng/mL after a 60-minute infusion. The steady-state AUC0–12h was 2349 ± 850 ng hour/mL.

Biotransformation.

It is estimated that, on average, less than 20% of tigecycline is metabolized before excretion. Following administration of 14C-tigecycline to healthy male volunteers, unchanged 14C-labeled material was recovered in urine and feces; the glucuronide, N-acetyl metabolite, and epimer of tigecycline were also present.

In vitro studies in human liver microsomes demonstrate that tigecycline does not inhibit metabolism mediated by any of the six cytochrome P450 (CYP) isoforms: 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 by competitive inhibition. Furthermore, tigecycline does not show nicotinamide adenine dinucleotide phosphate dependence in inhibiting CYP2C9, CYP2C19, CYP2D6, and CYP3A, suggesting the absence of suicidal inhibition of these CYP enzymes.

Breeding.

Total radioactivity in feces and urine following administration of 14C-tigecycline showed that 59% of the dose was excreted in feces and bile, and 33% in urine. Overall, the major route of elimination of tigecycline is biliary excretion of unchanged tigecycline. Minor routes include glucuronide formation and renal excretion of unchanged tigecycline. Total clearance of tigecycline following intravenous administration is 24 L/hour, with renal clearance accounting for approximately 13% of total. Tigecycline exhibits polyexponential elimination from serum; the mean elimination half-life after multiple doses is 42 hours, although there is considerable interindividual variability.

In vitro studies using Caco-2 cells demonstrate that tigecycline does not inhibit digoxin efflux, indicating that tigecycline is not a P-glycoprotein inhibitor. The in vitro results are consistent with the lack of effect of tigecycline on digoxin clearance from the in vivo drug interaction study described below (see section 4.5).

Based on in vitro studies using a cell line overexpressing P-glycoprotein, tigecycline is a substrate of P-glycoprotein. The potential contribution of P-glycoprotein-mediated transport to tigecycline disposition in vivo is unknown. Concomitant use of P-glycoprotein inhibitors (e.g., ketoconazole or cyclosporine) or P-glycoprotein inducers (e.g., rifampicin) may affect the pharmacokinetics of tigecycline.

Special patient groups.

The pharmacokinetics of a single dose of tigecycline were not altered in patients with mild hepatic impairment. However, in patients with moderate and severe hepatic impairment (Child-Pugh B and C), the systemic clearance of tigecycline was reduced by 25% and 55%, respectively, and the elimination half-life of tigecycline was prolonged by 23% and 43%, respectively (see Dosage and Administration).

Kidney dysfunction.

The pharmacokinetics of a single dose of tigecycline are not altered in patients with renal impairment (creatinine clearance < 30 mL/min, n=6). In patients with severe renal impairment, AUC was 30% higher than in patients with normal renal function (see Dosage and Administration).

Elderly patients.

In general, no differences were found between the pharmacokinetic parameters of elderly and younger healthy volunteers (see section "Method of administration and dosage").

Children.

The pharmacokinetics of tigecycline were studied in two studies. The first study included children aged 8–16 years (n=24) who received a single dose of tigecycline (0.5 mg/kg, 1 mg/kg, or 2 mg/kg, up to a maximum dose of 50 mg, 100 mg, and 150 mg, respectively) intravenously over 30 minutes. The second study was conducted in children aged 8–11 years who received multiple doses of tigecycline (0.75 mg/kg, 1 mg/kg, or 1.25 mg/kg, up to a maximum dose of 50 mg) intravenously every 12 hours over 30 minutes. Loading doses were not used in these studies. Pharmacokinetic parameters are shown in Table 2.

Table 2.

Dose normalized to 1 mg/kg, mean ± SD Cmax and AUC of tigecycline in children.

* Single dose - AUC0–∞, multiple dose - AUC0–12h.

The target AUC0–12h in adults following the recommended 100 mg loading dose and 50 mg every 12 hours was approximately 2500 ng•hr/mL.

Population pharmacokinetic analyses in both studies identified body weight as a covariate for tigecycline clearance in children aged 8 years and older. A dosing regimen of 1.2 mg/kg tigecycline every 12 hours (up to a maximum dose of 50 mg every 12 hours) for children aged 8–12 years and 50 mg every 12 hours for adolescents aged 12–18 years is likely to result in drug exposure similar to that observed in adults at the approved dosing regimen.

In these studies, higher Cmax values were observed in some children than in adults. Therefore, caution should be exercised in selecting the infusion rate of tigecycline in children.

Sex.

No clinically significant differences were found between tigecycline clearance in males and females. The AUC was determined to be 20% higher in females than in males.

Race.

Tigecycline clearance is independent of race.

Body weight.

Clearance, weight-adjusted clearance, and AUC were not significantly different in patients with different body weights, including patients weighing ≥ 125 kg. AUC was 24% lower in patients weighing ≥ 125 kg. Data are not available for patients weighing 140 kg or more.

Indication

Tygacil is prescribed to adults and children aged 8 years and older for the treatment of (see sections “Special instructions for use” and “Pharmacodynamics”):

complicated skin and soft tissue infections, except for infected diabetic foot (see section "Special instructions for use");

complicated intra-abdominal infections.

Tygacil should only be used in cases where other antibiotics are not suitable for use (see sections “Special instructions for use”, “Adverse reactions” and “Pharmacodynamics”).

Attention should be paid to official recommendations regarding the appropriate use of antibacterial agents.

Contraindication

Hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.

Patients with hypersensitivity to tetracycline antibiotics may be hypersensitive to tigecycline.

Interaction with other medicinal products and other types of interactions

Interaction studies were conducted only with adults.

Co-administration of tigecycline and warfarin (25 mg single dose) in healthy volunteers resulted in a 40% and 23% decrease in R-warfarin and S-warfarin clearance and a 68% and 29% increase in AUC, respectively. The mechanism of this interaction is still unknown. Based on the available data, it cannot be assumed that this interaction would lead to significant changes in the international normalized ratio. However, since tigecycline can prolong both prothrombin time and activated partial thromboplastin time, coagulation studies should be carefully monitored when tigecycline is co-administered with anticoagulants (see section 4.4). Warfarin did not affect the pharmacokinetic profile of tigecycline.

Tigecycline at recommended doses does not affect the rate or extent of absorption or clearance of digoxin (0.5 mg followed by 0.25 mg daily) in healthy adult volunteers. Digoxin does not affect the pharmacokinetic profile of tigecycline. Therefore, no dose adjustment is required when tigecycline is co-administered with digoxin.

Concomitant use of antibiotics with oral contraceptives may reduce the effectiveness of contraceptives.

Concomitant use of tigecycline and calcineurin inhibitors such as tacrolimus or ciclosporin may result in increased serum trough concentrations of calcineurin inhibitors. Therefore, serum calcineurin inhibitor concentrations should be monitored during treatment with tigecycline to avoid drug toxicity.

Tigecycline is a substrate for P-glycoprotein based on in vitro studies. Co-administration with P-glycoprotein inhibitors (e.g. ketoconazole or ciclosporin) or P-glycoprotein inducers (e.g. rifampicin) may affect the pharmacokinetics of tigecycline (see section 5.2).

Application features

In clinical trials in patients with complicated skin and soft tissue infections, complicated intra-abdominal infections, infected diabetic foot, nosocomial pneumonia, and in trials in patients with resistant pathogens, a higher mortality rate was observed in patients treated with tigecycline compared to patients treated with the comparator. The reasons for this remain unknown, but inferior efficacy and safety compared to the comparators used in the trials cannot be ruled out.

Superinfection.

In clinical studies in patients with complicated intra-abdominal infections, impaired surgical wound healing was associated with superinfection. Patients with impaired healing should be monitored for superinfection (see section 4.8).

Patients who develop superinfections, particularly nosocomial pneumonia, are likely to have poorer outcomes. Patients should be closely monitored for the development of superinfection. If a site of infection other than complicated skin and soft tissue infections or complicated intra-abdominal infections is identified after initiation of tigecycline, consideration should be given to the use of alternative antibacterial therapy that has been demonstrated to be effective in treating the specific type of infection(s) present.

Anaphylaxis.

Anaphylactic/anaphylactoid reactions, which are potentially life-threatening, have been reported with tigecycline (see sections 4.3 and 4.8).

Liver failure.

Cases of liver injury, predominantly cholestatic, including fatal cases of hepatic failure, have been reported in patients treated with tigecycline. Although the development of hepatic failure in patients treated with tigecycline may be due to underlying diseases or concomitant medications, the possible contribution of tigecycline to the development of this condition should be considered (see section 4.8).

Tetracycline class antibiotics.

Glycylcycline antibiotics are structurally similar to tetracycline antibiotics. Adverse reactions similar to those seen with tetracycline antibiotics may occur with tigecycline. Adverse reactions may include photosensitivity, pseudotumor cerebri, pancreatitis, and anti-anabolic effects resulting in increased blood urea nitrogen, azotemia, acidosis, and hyperphosphatemia (see Adverse Reactions).

Pancreatitis.

Acute pancreatitis, which may be severe, has been reported (frequency unknown) in association with tigecycline (see section 4.8). A diagnosis of acute pancreatitis should be considered in patients receiving tigecycline if they develop clinical symptoms, signs, or laboratory abnormalities consistent with acute pancreatitis. Most reported cases of pancreatitis have occurred at least 1 week after tigecycline administration. In some cases, pancreatitis has occurred in patients with no known risk factors for pancreatitis. Patients usually improve after discontinuation of tigecycline. Discontinuation of tigecycline should be considered if pancreatitis is suspected.

Coagulopathy

Tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time (APTT). In addition, hypofibrinogenemia has been reported with tigecycline. Therefore, coagulation parameters such as PT or other appropriate anticoagulation test, including blood fibrinogen, should be monitored before initiating treatment with tigecycline and regularly during treatment. Particular caution is recommended in patients with serious medical conditions and in patients also receiving anticoagulants.

Experience with the use of tigecycline in infections in patients with severe underlying diseases is limited.

Clinical trials of tigecycline for the treatment of complicated skin and soft tissue infections have most often involved patients with subcutaneous tissue inflammation (58.6%) and subsequent severe abscesses (24.9%). Patients with severe underlying diseases such as immunosuppression, infected pressure ulcers, or patients requiring treatment for more than 14 days (e.g. necrotizing fasciitis) were excluded. A limited number of patients with comorbidities such as diabetes mellitus (25.8%), peripheral vascular disease (10.4%), intravenous drug users (4.0%) and HIV infection (1.2%) were also included. There is also limited experience in patients with concomitant bacteremia (3.4%). Therefore, caution should be exercised in treating these patients. The results of a large study involving patients with infected diabetic feet showed lower efficacy of tigecycline compared to the reference drug, therefore its use is not recommended in this group of patients (see section “Indications”).

Clinical trials of tigecycline for the treatment of complicated intra-abdominal infections were most commonly conducted in patients with complicated appendicitis (50.3%), as well as patients with less common diagnoses such as complicated cholecystitis (9.6%), intestinal perforation (9.6%), intra-abdominal abscess (8.7%), perforated gastric or duodenal ulcer (8.3%), peritonitis (6.2%), and complicated diverticulitis (6.0%). 77.8% of these patients had peritonitis that was detected at surgery. A limited number of patients with severe underlying diseases were included in the study: immunocompromised, clinical severity according to the ARASNE II scale > 15 (3.34%), surgically detected multiple intra-abdominal abscesses (11.4%). There is also limited experience in treating patients with concomitant bacteremia (5.6%). Therefore, caution should be exercised when treating such patients.

When tigecycline is used in patients with severe complicated intra-abdominal infections due to intestinal perforation, early sepsis or septic shock, the use of combination antibacterial therapy should be considered (see section 4.8).

The effect of cholestasis on the pharmacokinetics of tigecycline has not been clearly established. Biliary excretion of tigecycline accounts for approximately 50% of the total amount excreted in the body. Therefore, patients with cholestasis should be carefully monitored.

Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or after the use of any antibacterial agent (see Adverse Reactions).

The use of tigecycline may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be closely monitored during treatment (see section 4.8).

Studies with tigecycline in rats have shown changes in bone color. Administration of tigecycline during tooth development may result in permanent changes in tooth color in humans (see section 4.8).

Children.

Clinical experience with tigecycline for the treatment of infections in children aged 8 years and older is very limited (see sections 4.8 and 5.1). Therefore, the use of this drug should be limited to clinical situations where there is no alternative antibacterial therapy.

Adverse reactions such as nausea and vomiting are very common in children and adolescents (see section "Adverse reactions"). The possible development of dehydration should be taken into account. In children, it is better to administer the drug by intravenous infusion over 60 minutes.

As in adults, abdominal pain has been reported frequently in children. This pain may be indicative of pancreatitis. If pancreatitis develops, tigecycline should be discontinued.

Before starting and during the use of tigecycline, liver function tests, coagulation parameters, blood counts, amylase and lipase levels should be regularly performed.

Tygacil should not be used in children under 8 years of age due to a lack of information on the safety and efficacy of the drug in this age group and because tigecycline may be associated with persistent tooth discoloration (see section 4.8).

Information about excipients.

Tygacil contains less than 1 mmol sodium (23 mg) per 5 ml solution. Patients on a controlled sodium diet may be informed that this medicinal product is essentially sodium-free.

Use during pregnancy or breastfeeding

Pregnancy. There are no or limited amount of data from the use of tigecycline in pregnant women. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown. As with tetracycline antibiotics, tigecycline may cause permanent dental damage (discoloration and enamel defects) and delayed ossification in the fetus when exposed in utero in the second half of pregnancy, as well as in children under 8 years of age due to accumulation in tissues with high calcium metabolism and the formation of chelate complexes containing calcium (see section "Special instructions for use"). Tigecycline should not be used in pregnancy, except in clinical cases when the woman requires the use of tigecycline.

Breast-feeding. It is not known whether tigecycline/metabolites are excreted in human milk. Available animal data show that tigecycline/metabolites are excreted in milk. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tigecycline therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility. The effect of tigecycline on human fertility has not been studied. Nonclinical studies of tigecycline in rats indicate no harmful effects on fertility or reproductive function. No drug-related effects on ovaries or ovarian cycles were observed in female rats at doses up to 4.7 times the human daily dose based on AUC.

The ability to influence the reaction speed when driving or working with other mechanisms

Dizziness may occur when using tigecycline, which may affect the ability to drive and use machines (see section "Adverse reactions").

Method of administration and doses

Dosage.

Adults.

The initial recommended dose is 100 mg, followed by 50 mg every 12 hours for 5–14 days.

Children and adolescents (ages 8 to 18).

Children 8 to 12 years of age: 1.2 mg/kg tigecycline every 12 hours intravenously, maximum dose 50 mg every 12 hours for 5–14 days.

Adolescents 12 to 18 years of age: 50 mg every 12 hours for 5–14 days.

The duration of treatment should be selected depending on the severity of the disease, the location of the infection and the patient's clinical response.

Elderly patients.

No dose adjustment is required for elderly patients (see Pharmacokinetics).

Liver dysfunction.

No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh grades A and B).

In patients (including children) with severe hepatic impairment (Child-Pugh C), the dose of tigecycline should be reduced by 50%. The adult dose should be reduced to 25 mg every 12 hours after a 100 mg loading dose. The drug should be used with caution and the response to treatment should be monitored in patients with severe hepatic impairment (Child-Pugh C) upon administration (see sections 4.4 and 5.2).

Kidney dysfunction.

No dose adjustment is required for patients with renal impairment or patients undergoing hemodialysis (see Pharmacokinetics).

Method of application.

Tigecycline should only be administered by intravenous infusion over 30 to 60 minutes (see section 4.4). In children, it is preferable to administer tigecycline as an intravenous infusion over 60 minutes (see section 4.4).

Information on reconstitution and dilution of the medicinal product before use.

To achieve a concentration of 10 mg/mL tigecycline, the powder should be reconstituted with 5.3 mL of 0.9% sodium chloride injection (9 mg/mL), 5% dextrose injection (50 mg/mL), or lactose-free Ringer's injection. The contents of the vial should be gently mixed by swirling until the powder is completely dissolved. 5 mL of the resulting solution should then be immediately withdrawn from the vial and injected into a 100 mL intravenous infusion bag or other suitable infusion container (e.g., glass vial).

To obtain a 100 mg dose, reconstitute 2 vials in a 100 mL intravenous infusion bag or other suitable infusion container (e.g., glass vial).

Note: the vial contains a 6% excess, so 5 ml of the prepared solution is equivalent to 50 mg of active ingredient.

Tigecycline should be administered intravenously through a separate intravenous line or a Y-line. If the same line is used for sequential administration of multiple active substances, it should be flushed with 0.9% sodium chloride injection (9 mg/ml) or 5% dextrose injection (50 mg/ml) before and after tigecycline administration. When administering through a shared line, infusion solutions compatible with both tigecycline and other medicinal products administered through the same line should be used (see section 4.5).

The vial of medicine is intended for single use; any unused product or waste material should be disposed of in accordance with local requirements.

Compatible solutions for intravenous administration:

0.9% sodium chloride solution for injection (9 mg/ml);

5% dextrose solution for injection (50 mg/mL);

Ringer's solution with lactose for injection.

When administered via a Y-line catheter, the compatibility of tigecycline solution prepared using 0.9% sodium chloride solution has been demonstrated for the following drugs or diluents: amikacin, dobutamine, dopamine hydrochloride, gentamicin, haloperidol, Ringer's solution with lactose, lidocaine hydrochloride, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (EDTA-containing formulation), potassium chloride, propofol, ranitidine hydrochloride, theophylline, and tobramycin.

Children

The safety and efficacy of Tygacil in children under 8 years of age have not been established. There are no data on this.

Tygacil should not be used in children under 8 years of age due to tooth discoloration (see sections “Special instructions for use” and “Pharmacodynamics”).

Overdose

There is no specific information on the treatment of overdose. After a single intravenous administration of 300 mg tigecycline over 60 minutes to healthy volunteers, an increased incidence of nausea and vomiting was observed.

Tigecycline is not removed by hemodialysis in significant amounts.

Side effects

A total of 2,393 patients with complicated skin and soft tissue infections and complicated intra-abdominal infections were treated during phase 3 and 4 clinical trials of tigecycline.

During clinical trials, the most common adverse reactions associated with the use of the drug were nausea (21%) and vomiting (13%). These reactions were in most cases mild or moderate in severity, usually developed at the beginning of treatment (after 1-2 days) and were reversible.

Adverse reactions reported with tigecycline, including those identified during clinical trials and post-marketing experience, are listed below with the following frequency: very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1,000 and < 1/100; rare: ≥ 1/10,000 and < 1/1,000; very rare: < 1/10,000; frequency unknown (cannot be estimated from the available data).

Adverse drug reactions identified after the drug was marketed are indicated by the symbol "*".

Infections and invasions.

Common: sepsis/septic shock, pneumonia, abscess, infections.

From the blood and lymphatic system.

Common: prolonged activated partial thromboplastin time, prolonged prothrombin time.

Uncommon: thrombocytopenia, increased international normalized ratio.

Rare: hypofibrinogenemia.

Frequency unknown: hypofibrinogenemia.

From the immune system.

Frequency unknown: anaphylactic/anaphylactoid reactions* (see sections "Contraindications" and "Special warnings and precautions for use").

Metabolic disorders and nutritional disorders.

Common: hypoglycemia, hypoproteinemia.

From the nervous system.

Common: dizziness.

From the vascular system.

Common: phlebitis.

Uncommon: thrombophlebitis.

From the gastrointestinal tract.

Very common: nausea, vomiting, diarrhea.

Common: abdominal pain, dyspepsia, anorexia.

Uncommon: acute pancreatitis (see section "Special warnings and precautions for use").

On the part of the hepatobiliary system.

Common: increased aspartate levels