MIMS Class : Other Antibiotics
 

Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus group (includes S. anginosus, S. intermedius and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens and Peptostreptococcus micros.

Community-acquired pneumonia caused by Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae (penicillin-susceptible isolates only), including cases with concurrent bacteremia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila.

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to tigecycline. Tygacil may be initiated as empiric monotherapy before results of these tests are known.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tygacil and other antibacterial drugs, it should only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Tygacil is administered by IV infusion. The infusion time should be approximately 30-60 min (see Instructions for Use and Handling under Cautions for Usage).

The recommended duration of treatment with tigecycline for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5-14 days. The recommended duration of treatment with tigecycline for community-acquired pneumonia is 7-14 days. The duration of therapy should be guided by the severity and site of the infection and the patient’s clinical and bacteriological progress.

Hepatic Insufficiency: No dosage adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh A and B).

Based on the pharmacokinetic profile of tigecycline in patients with severe hepatic impairment (Child-Pugh C), the dose of tigecycline should be altered to 100 mg followed by 25 mg every 12 hrs. Patients with severe hepatic impairment (Child-Pugh C) should be treated with caution and monitored for treatment response (see Pharmacokinetics under Actions).

Renal Insufficiency: No dosage adjustment is necessary in patients with renal impairment or in patients undergoing hemodialysis (see Pharmacokinetics under Actions).

Children: Safety and effectiveness have not been established. Therefore, use in patients <18 years is not recommended.

Elderly: No dosage adjustment is necessary in elderly patients (see Pharmacokinetics under Actions).

Gender: No dosage adjustment is necessary based on gender (see Pharmacokinetics under Actions).

Race: No dosage adjustment is necessary based on race (see Pharmacokinetics under Actions).

Abuse and Dependence: Drug abuse and dependence have not been demonstrated and are unlikely.

Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Therefore, tigecycline should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics.

Results of studies in rats with tigecycline have shown bone discoloration. Tigecycline may be associated with permanent teeth discoloration in humans during teeth development.

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 subsequent to the administration of any antibacterial agent.

Glycylcyclines are structurally similar to tetracyclines and may have similar adverse effects. Such effects may include: Photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of tigecycline.

The safety and efficacy of tigecycline in patients with hospital-acquired pneumonia have not been established. In a study of patients with hospital-acquired pneumonia, patients were randomized to receive tigecycline (100 mg initially, then 50 mg every 12 hrs) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received tigecycline had lower cure rates (47.9% vs 70.1% for the clinically evaluable population) and greater mortality [25/131 (19.1%) vs 15/122 (12.3%)] than the comparator.

As with other antibiotic preparations, use of Tygacil may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.

Effects on the Ability to Drive or Operate Machinery: Tigecycline can cause dizziness (see Adverse Reactions), which may impair the ability to drive and/or operate machinery.

Use in pregnancy: Tigecycline may cause fetal harm when administered to a pregnant woman. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues.

There are no adequate and well-controlled studies of tigecycline in pregnant women. Tigecycline should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Tigecycline has not been studied for use during labor and delivery.

Use in lactation: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tigecycline is administered to a nursing woman.

Use in children: Safety and effectiveness in patients <18 years have not been established. Therefore, use in patients <18 years is not recommended.

Use in the elderly: Of the total number of subjects who received tigecycline in phase 3 clinical studies (n=2514), 664 were ≥65, while 228 were ≥75. No unexpected overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity to adverse events of some older individuals cannot be ruled out.

For patients who received tigecycline, the following adverse reactions were reported:

Blood and Lymphatic System Disorders: Common: Prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT). Uncommon: Increased international normalized ratio (INR).

Immune System Disorders: Undetermined frequency: Anaphylaxis/anaphylactoid reactions.

Metabolism and Nutrition Disorders: Common: Bilirubinemia, increased blood urea nitrogen (BUN), hypoproteinemia.

Nervous System Disorders: Common: Dizziness.

Cardiac Disorders: Common: Phlebitis. Uncommon: Thrombophlebitis.

Gastrointestinal Disorders: Very Common: Nausea, vomiting, diarrhea. Common: Anorexia, abdominal pain, dyspepsia. Uncommon: Acute pancreatitis.

Hepatobiliary Disorders: Common: Elevated aspartate aminotransferase (AST) in serum, elevated alanine aminotransferase (ALT) in serum*. Uncommon: Jaundice.

*AST and ALT abnormalities in tigecycline-treated patients were reported more frequently in the post-therapy period than in those in comparator-treated patients, which occurred more often on therapy.

Skin and Subcutaneous Tissue Disorders: Common: Pruritus, rash.

General Disorders and Administration Site Conditions: Common: Headache. Uncommon: Inflammation, pain, reaction, edema and phlebitis at the injection site.

Investigations: Common: Elevated serum amylase.

In Phase 3 studies that included a comparator and employed a 1:1 randomization, death occurred in 4.7% (107/2274) of patients receiving tigecycline and 3.8% (85/2264) of patients receiving comparator drugs; this difference is not statistically significant and relationship to treatment cannot be established. In addition, no significant differences were observed between treatments by indication. Generally, deaths represented complications of the underlying disease or progression of disease.

The most common treatment-emergent adverse reactions in patients treated with tigecycline were nausea 26.4% (16.9% mild; 8.1% moderate; 1.3% severe) and vomiting 18.1% (11% mild; 6.1% moderate; 1% severe). In general, nausea and vomiting occurred early (days 1-2).

Discontinuation from tigecycline was most frequently associated with nausea (1.1%) and vomiting (1.1%).

Concomitant administration of tigecycline (100 mg followed by 50 mg every 12 hrs) and warfarin (25 mg single dose) to healthy subjects resulted in a decrease in clearance of R-warfarin and S-warfarin by 40% and 23%, and an increase in AUC by 68% and 29%, respectively. Tigecycline did not significantly alter the effects of warfarin on increased international normalized ratio (INR). In addition, warfarin did not affect the pharmacokinetic profile of tigecycline. However, prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin.

In vitro studies in human liver microsomes indicate that tigecycline does not inhibit metabolism mediated by any of the following 6 cytochrome CYP-450 isoforms: 1A2, 2C8, 2C9, 2C19, 2D6 and 3A4. Therefore, tigecycline is not expected to alter the metabolism of drugs metabolized by these enzymes. In addition, because it is not extensively metabolized, clearance of tigecycline is not expected to be affected by drugs that inhibit or induce the activity of these CYP-450 isoforms.

Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.

Interference with Laboratory and other Diagnostic Tests: There are no reported drug-laboratory test interactions.

Incompatibilities: Compatible IV solutions include 0.9% Sodium Chloride Injection USP and 5% Dextrose Injection USP.

Tigecycline is compatible with the following drugs or diluents when administered simultaneously through the same line: Amikacin, dobutamine, dopamine HCl, gentamicin, haloperidol, Lactated Ringer’s, lidocaine HCl, morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, propofol, ranitidine HCl, theophylline and tobramycin.

The following drugs should not be administered simultaneously through the same line as tigecycline: Amphotericin B and diazepam.

Tygacil must not be mixed with other medicinal products for which compatibility data are not available.

Tygacil may be administered IV through a dedicated line or through a Y-site. If the same IV line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of Tygacil with either 0.9% sodium chloride or 5% dextrose solution for injection. Injection should be made with an infusion solution compatible with tigecycline and any other medicinal product(s) via this common line (see Interactions: Incompatibilities).

Once reconstituted, the solution should be yellow to orange in color, if not, the solution should be discarded.

Once reconstituted, tigecycline may be stored at room temperature (25°C) for up to 24 hrs (up to 6 hrs in the vial and the remaining time in the IV bag). Alternatively, tigecycline may be stored refrigerated at 2-8°C (36-46°F) for up to 45 hrs following immediate transfer of the reconstituted solution into the IV bag.

Reconstituted solution must be transferred and further diluted for IV infusion.

Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure based on dilution methods (broth, agar or microdilution) or equivalent using standardized inoculum and concentrations of tigecycline. For broth dilution tests for aerobic organisms, MICs must be determined in testing medium that is fresh (<12 hrs old). The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with tigecycline 15 mcg to test the susceptibility of microorganisms to tigecycline. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for tigecycline. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 15-mcg tigecycline disk should be interpreted according to the criteria in Table 1.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small, uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound reaches the concentrations usually achievable; other therapy should be selected.

Quality Control: As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standard tigecycline powder should provide the MIC values provided in Table 2. For the diffusion technique using the 15-mcg tigecycline disk, laboratories should use the criteria provided in Table 2 to test the quality control strains.

The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. The following information provides only approximate guidance on the probability as to whether the microorganism will be susceptible to tigecycline or not:

Susceptible: Gram-Positive Aerobes: Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecalis* (includes vancomycin-susceptible strains), Enterococcus faecalis (includes vancomycin-resistant strains), Enterococcus faecium (includes vancomycin-susceptible and -resistant strains), Enterococcus gallinarum, Listeria monocytogenes, Staphylococcus aureus* (includes methicillin-susceptible and -resistant strains, including isolates that bear molecular and virulence markers commonly associated with community-acquired MRSA including SCCmec type IV element and the pvl gene), Staphylococcus epidermidis (includes methicillin-susceptible and -resistant strains), Staphylococcus haemolyticus, Streptococcus agalactiae*, Streptococcus anginosus* (includes S. anginosus, S. intermedius, S. constellatus), Streptococcus pyogenes*, Streptococcus pneumoniae* ( penicillin-susceptible isolates), Streptococcus pneumoniae ( penicillin-resistant isolates), viridans group streptococci.

Gram-Negative Aerobes: Acinetobacter calcoaceticus/ baumannii complex, Aeromonas hydrophila, Citrobacter freundii*, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae*, Escherichia coli* (including ESBL-producing strains), Haemophilus influenzae*, Haemophilus parainfluenzae, Klebsiella oxytoca*, Klebsiella pneumoniae* (including ESBL-producing strains), Klebsiella pneumoniae (including AmpC-producing strains), Legionella pneumophila*, Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Salmonella enterica ser. Enteritidis, Paratyphi, Typhi and Typhimurium; Shigella boydii, Shigella dysenteriae, Shigella flexneri, Serratia marcescens, Shigella sonnei, Stenotrophomonas maltophilia.

Anaerobic Bacteria: Bacteroides fragilis*, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron*, Bacteroides uniformis*, Bacteroides vulgatus*, Clostridium difficile, Clostridium perfringens*, Peptostreptococcus spp, Peptostreptococcus micros*, Porphyromonas and Prevotella spp.

Atypical Bacteria: Chlamydia pneumoniae*, Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, Mycoplasma pneumoniae*.

*Clinical efficacy has been demonstrated for susceptible isolates in the approved clinical indications.

Resistant: Gram-Negative Aerobes: Pseudomonas aeruginosa.

Anaerobic Bacteria: No naturally occurring species has been found to be inherently resistant to tigecycline.

Resistance: There have been no cross-resistance observed between tigecycline and other antibiotics.

Tigecycline is able to overcome the 2 major tetracycline resistance mechanisms, ribosomal protection and efflux.

In in vitro studies, no antagonism has been observed between tigecycline and any other commonly used antibiotic class.

Clinical Efficacy: Complicated Skin and Skin Structure Infections: Tigecycline was evaluated in adults for the treatment of complicated skin and skin structure infections (cSSSI) in 2 randomized, double-blind, active-controlled, multinational, multicenter studies. These studies compared tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) with vancomycin (1 g IV every 12 hrs)/aztreonam (2 g IV every 12 hrs) for 5-14 days. Patients with complicated deep soft tissue infections including wound infections and cellulitis (greater than or equal to 10 cm, requiring surgery/drainage or with complicated underlying disease), major abscesses, infected ulcers and burns were enrolled in the studies. The primary efficacy endpoint was the clinical response at the test of cure (TOC) visit in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) patients (see Table 3).

Clinical cure rates at test of cure (TOC) by pathogen in microbiologically evaluable patients with complicated skin and skin structure infections are presented in Table 4.

Complicated Intra-abdominal Infections: Tigecycline was evaluated in adults for the treatment of complicated intra-abdominal infections (cIAI) in 2 randomized, double-blind, active-controlled, multinational, multicenter studies. These studies compared tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) with imipenem/cilastatin (500 mg IV every 6 hrs) for 5-14 days. Patients with complicated diagnoses including appendicitis, cholecystitis, diverticulitis, gastric/duodenal perforation, intra-abdominal abscess, perforation of intestine and peritonitis were enrolled in the studies. The primary efficacy endpoint was the clinical response at the test of cure (TOC) visit for the co-primary populations of the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) patients (see Table 5).

Clinical cure rates at test of cure (TOC) by pathogen in microbiologically evaluable patients with complicated intra-abdominal infections are presented in Table 6.

Community-Acquired Pneumonia: Tigecycline was evaluated in adults for the treatment of community-acquired pneumonia (CAP) in 2 randomized, double-blind, active-controlled, multinational, multicenter studies (Studies 308 and 313). These studies compared tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) with levofloxacin (500 mg IV every 12 or 24 hrs). In one study (Study 308), after at least 3 days of IV therapy, a switch to oral levofloxacin (500 mg daily) was permitted for both treatment arms. Total therapy was 7-14 days. Patients with community-acquired pneumonia who required hospitalization and IV therapy were enrolled in the studies. The primary efficacy endpoint was the clinical response at the test of cure (TOC) visit in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) patients (see Table 7). Clinical cure rates at TOC by pathogen in microbiologically evaluable patients are presented in Table 8.

Vancomycin-Resistant Enterococcus (VRE) spp and Methicillin-Resistant Staphylococcus aureus (MRSA): Tigecycline was evaluated in adults for the treatment of various serious infections (cIAI, cSSSI and other infections) due to VRE and MRSA in Study 307.

Study 307 was a randomized, double-blind, active-controlled, multinational, multicenter study evaluating tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) and vancomycin (1 g IV every 12 hrs) for the treatment of infections due to methicillin-resistant Staphylococcus aureus (MRSA) and evaluating tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) and linezolid (600 mg IV every 12 hrs) for the treatment of infections due to vancomycin-resistant Enterococcus (VRE) for 7-28 days. Patients with cIAI, cSSSI and other infections were enrolled in this study. The primary efficacy endpoint was the clinical response at the TOC visit for the co-primary populations of the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) patients. See Table 9 for MRSA and Table 10 for VRE.

Resistant Gram-Negative Pathogens: Tigecycline was evaluated in adults for the treatment of various serious infections (cIAI, cSSSI, CAP and other infections) due to resistant gram-negative pathogens in Study 309.

Study 309 was an open-label, multinational, multicenter study evaluating tigecycline (100 mg IV initial dose followed by 50 mg every 12 hrs) for the treatment of infections due to resistant gram-negative pathogens for 7-28 days. Patients with cIAI, cSSSI, CAP and other infections were enrolled in this study. The primary efficacy endpoint was the clinical response at the TOC visit for the co-primary populations of the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) patients. See Table 11.

Rapidly Growing Mycobacterial Infections: In uncontrolled clinical studies and compassionate-use experience from 8 countries, 52 patients with rapidly growing mycobacterial infections (most frequently M. abscessus lung disease) were treated with tigecycline, along with other antibiotics. The mean and median durations of treatment were approximately 5½ months and 3 months, respectively (range: 3 days to approximately 3 ½ years). Approximately half of the patients achieved clinical improvement (ie, improvement in signs and symptoms of lung disease, or healing of wound, skin lesions or nodules in disseminated disease). Approximately half of the patients required dose reductions or discontinued treatment due to nausea, vomiting or anorexia.

Pharmacokinetics: The mean pharmacokinetic parameters of tigecycline for this dosage regimen after single and multiple IV doses are summarized in Table 12.

Intravenous infusions of tigecycline should be administered over approximately 30-60 min.

Absorption: Tigecycline is administered IV and therefore has 100% bioavailability.

Distribution: The in vitro plasma protein-binding of tigecycline ranges from approximately 71-89% at concentrations observed in clinical studies (0.1-1 mcg/mL). Animal and human pharmacokinetic studies have demonstrated that tigecycline readily distributes to tissues. In rats receiving a single or multiple doses of 14C-tigecycline, radioactivity was well distributed to most tissues, with the highest overall exposure observed in bone, bone marrow, salivary glands, thyroid gland, spleen and kidney. In humans, the steady-state volume of distribution of tigecycline averaged 500-700 L (7-9 L/kg), indicating that tigecycline is extensively distributed beyond the plasma volume and into the tissues of humans.

Two studies examined the steady-state pharmacokinetic profile of tigecycline in specific tissues or fluids of healthy subjects receiving tigecycline 100 mg followed by 50 mg every 12 hrs. In a bronchoalveolar lavage study, the tigecycline AUC0-12 hrs (134 mcg·hr/mL) in alveolar cells was approximately 77.5-fold higher than the AUC0-12 hrs in the serum of these subjects and the AUC0-12 hrs (2.28 mcg·hr/mL) in epithelial lining fluid was approximately 32% higher than the AUC0-12 hrs in serum. In a skin blister study, the AUC0-12 hrs (1.61 mcg·hr/mL) of tigecycline in skin blister fluid was approximately 26% lower than the AUC0-12 hrs in the serum of these subjects.

In a single-dose study, tigecycline 100 mg was administered to subjects prior to undergoing elective surgery or medical procedure for tissue extraction. Tissue concentrations at 4 hrs after tigecycline administration were measured in the following tissue and fluid samples: Gallbladder, lung, colon, synovial fluid and bone. Tigecycline attained higher concentrations in tissues versus serum in gallbladder (38-fold, n=6), lung (3.7-fold, n=5) and colon (2.3-fold, n=6). The concentration of tigecycline in these tissues after multiple doses has not been studied.

Metabolism: Tigecycline is not extensively metabolized. In vitro studies with tigecycline using human liver microsomes, liver slices and hepatocytes led to the formation of only trace amounts of metabolites. In healthy male volunteers following the administration of 14C-tigecycline, tigecycline was the primary 14C-labeled material recovered in urine and feces, but a glucuronide, an N-acetyl metabolite and a tigecycline epimer (each at no >10% of the administered dose) were also present.

Elimination: The recovery of the total radioactivity in feces and urine following administration of 14C-tigecycline indicates that 59% of the dose is eliminated by biliary/fecal excretion and 33% is excreted in urine. Overall, the primary route of elimination for tigecycline is biliary excretion of unchanged tigecycline. Glucuronidation and renal excretion of unchanged tigecycline are secondary routes.

Special Populations: Hepatic Insufficiency: In a study comparing 10 patients with mild hepatic impairment (Child Pugh A), 10 patients with moderate hepatic impairment (Child Pugh B) and 5 patients with severe hepatic impairment (Child Pugh C) to 23 age- and weight-matched healthy control subjects, the single-dose pharmacokinetic disposition of tigecycline was not altered in patients with mild hepatic impairment. However, systemic clearance of tigecycline was reduced by 25% and the half-life of tigecycline was prolonged by 23% in patients with moderate hepatic impairment (Child Pugh B). In addition, systemic clearance of tigecycline was reduced by 55%, and the half-life of tigecycline was prolonged by 43% in patients with severe hepatic impairment (Child Pugh C).

Based on the pharmacokinetic profile of tigecycline, no dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and B). However, in patients with severe hepatic impairment (Child Pugh C), the dose of Tygacil should be altered to 100 mg followed by 25 mg every 12 hrs. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response (see Dosage & Administration: Hepatic Insufficiency).

Renal Insufficiency: A single-dose study compared 6 subjects with severe renal impairment (creatinine clearance less than or equal to 30 mL/min), 4 end-stage renal disease (ESRD) patients receiving tigecycline 2 hrs before hemodialysis, 4 ESRD patients receiving tigecycline after hemodialysis and 6 healthy control subjects. The pharmacokinetic profile of tigecycline was not altered in any of the renally impaired patient groups, nor was tigecycline removed by hemodialysis. No dosage adjustment of tigecycline is necessary in patients with renal impairment or in patients undergoing hemodialysis (see Dosage & Administration: Renal Insufficiency).

Pediatric Patients: The pharmacokinetics of tigecycline in patients <18 years has not been established.

Elderly Patients: No overall differences in pharmacokinetics were observed between healthy elderly subjects and younger subjects. Therefore, no dosage adjustment is necessary based on age.

Gender: There were no differences in the clearance of tigecycline between men and women. Therefore, no dosage adjustment is necessary based on gender.

Race: There were no differences in the clearance of tigecycline based on race.