Tigecycline

TYGACIL is a tetracycline class antibacterial indicated in patients 18 years of age and older for:

• Complicated skin and skin structure infections ( 1.1 )
• Complicated intra-abdominal infections ( 1.2 )
• Community-acquired bacterial pneumonia ( 1.3 ) Limitations of Use : TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia ( 1.4 ). To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only to treat infections that are proven or strongly suspected to be caused by bacteria ( 1.5 ).

1.1 Complicated Skin and Skin Structure Infections TYGACIL is indicated in patients 18 years of age and older for the treatment of complicated skin and skin structure infections caused by susceptible isolates of Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus ), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis.

1.2 Complicated Intra-abdominal Infections TYGACIL is indicated in patients 18 years of age and older for the treatment of complicated intra-abdominal infections caused by susceptible isolates of Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus ), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

1.3 Community-Acquired Bacterial Pneumonia TYGACIL is indicated in patients 18 years of age and older for the treatment of community-acquired bacterial pneumonia caused by susceptible isolates of Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae , and Legionella pneumophila .

1.4 Limitations of Use TYGACIL is not indicated for the treatment of diabetic foot infections. A clinical trial failed to demonstrate non-inferiority of TYGACIL for treatment of diabetic foot infections. TYGACIL is not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia. In a comparative clinical trial, greater mortality and decreased efficacy were reported in TYGACIL-treated patients [see Warnings and Precautions (5.2) ].

1.5 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only 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. 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.

For Injection: Each single-dose 10 mL glass vial contain 50 mg of tigecycline as an orange lyophilized powder for reconstitution. For Injection : 50 mg, lyophilized powder for reconstitution in a single-dose 10 mL vial. ( 3 )

TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline or to any of the excipients. Reactions have included anaphylactic reactions [see Warnings and Precautions (5.3) and Adverse Reactions (6.2) ].

• Known hypersensitivity to tigecycline. ( 4 )

• All-Cause Mortality : A meta-analysis of Phase 3 and 4 clinical trials demonstrated an increase in all-cause mortality in TYGACIL-treated patients compared to controls with a risk difference of 0.6% (95% CI 0.1, 1.2). The cause of this increase has not been established. An increase was also seen in a meta-analysis limited to the approved indications [0.6% (95% CI 0.0, 1.2)]. The greatest difference in mortality was seen in TYGACIL-treated patients with ventilator-associated pneumonia. ( 5.1 , 5.2 )
• Anaphylactic Reactions : have been reported with TYGACIL, and may be life-threatening. Avoid use in patients with known hypersensitivity to tetracyclines. ( 5.3 )
• Hepatic Adverse Effects : have been reported with TYGACIL. Patients who develop abnormal liver function tests during TYGACIL therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. ( 5.4 )
• Pancreatitis : including fatalities, has been reported with TYGACIL. If pancreatitis is suspected, then consider stopping TYGACIL. ( 5.5 )
• Monitoring Blood Coagulation Parameters: Hypofibrinogenemia has been reported with TYGACIL. Monitor blood coagulation parameters, including fibrinogen, at baseline and regularly during treatment with TYGACIL. ( 5.6 )
• Tooth Discoloration and Enamel Hypoplasia : The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. ( 5.7 )
• Inhibition of Bone Growth : The use of TYGACIL during the second and third trimester of pregnancy, infancy, and childhood up to the age of 8 years may cause reversible inhibition of bone growth. ( 5.8 )
• Clostridioides difficile- Associated Diarrhea (CDAD) : evaluate if diarrhea occurs. ( 5.9 )

5.1 All-Cause Mortality An increase in all-cause mortality has been observed in a meta-analysis of Phase 3 and 4 clinical trials in TYGACIL-treated patients versus comparator-treated patients. In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, the adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between TYGACIL and comparator-treated patients. An analysis of mortality in all trials conducted for approved indications (cSSSI, cIAI, and CABP), including post-market trials showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2). The cause of this mortality difference has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities. TYGACIL should be reserved for use in situations when alternative treatments are not suitable [see Boxed Warning , Indications and Usage (1.4) , Warnings and Precautions (5.2) and Adverse Reactions (6.1) ].

5.2 Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia A trial of patients with hospital acquired, including ventilator-associated, pneumonia failed to demonstrate the efficacy of TYGACIL. In this trial, patients were randomized to receive TYGACIL (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received TYGACIL had lower cure rates (47.9% versus 70.1% for the clinically evaluable population). In this trial, greater mortality was seen in patients with ventilator-associated pneumonia who received TYGACIL (25/131 [19.1%] versus 15/122 [12.3%] in comparator-treated patients) [see Adverse Reactions (6.1) ] . Particularly high mortality was seen among TYGACIL-treated patients with ventilator-associated pneumonia and bacteremia at baseline (9/18 [50.0%] versus 1/13 [7.7%] in comparator-treated patients).

5.3 Anaphylactic Reactions Anaphylactic reactions have been reported with nearly all antibacterial agents, including TYGACIL, and may be life-threatening. TYGACIL is structurally similar to tetracycline-class antibacterial drugs and should be avoided in patients with known hypersensitivity to tetracycline-class antibacterial drugs.

5.4 Hepatic Adverse Effects Increases in total bilirubin concentration, prothrombin time and transaminases have been seen in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. Hepatic dysfunction may occur after the drug has been discontinued.

5.5 Pancreatitis Acute pancreatitis, including fatal cases, has occurred in association with tigecycline treatment. The diagnosis of acute pancreatitis should be considered in patients taking tigecycline who develop clinical symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis. Cases have been reported in patients without known risk factors for pancreatitis. Patients usually improve after tigecycline discontinuation. Consideration should be given to the cessation of the treatment with tigecycline in cases suspected of having developed pancreatitis [see Adverse Reactions (6.2) ] .

5.6 Monitoring of Blood Coagulation Parameters Hypofibrinogenemia has been reported in patients treated with TYGACIL [see Adverse Reactions (6.2) ] . Obtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with TYGACIL.

5.7 Tooth Discoloration and Enamel Hypoplasia The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of tetracyclines, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Advise the patient of the potential risk to the fetus if TYGACIL is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4) ].

5.8 Inhibition of Bone Growth The use of TYGACIL during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the tetracycline was discontinued. Advise the patient of the potential risk to the fetus if TYGACIL is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4) ].

5.9 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. […]

The following serious adverse reactions are described elsewhere in the labeling:

• All-Cause Mortality [see Boxed Warning and Warnings and Precautions (5.1) ]
• Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia [see Warnings and Precautions (5.2) ]
• Anaphylaxis [ Warning and Precautions (5.3) ]
• Hepatic Adverse Effects [ Warnings and Precautions (5.4) ]
• Pancreatitis [ Warnings and Precautions (5.5) ] The most common adverse reactions (incidence >5%) are nausea, vomiting, diarrhea, abdominal pain, headache, and increased SGPT. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of adverse reactions through test of cure reported in ≥2% of patients in these trials. Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reported in ≥ 2% of Patients Treated in Clinical Studies Body System Adverse Reactions TYGACIL (N=2514) Comparators Vancomycin/Aztreonam, Imipenem/Cilastatin, Levofloxacin, Linezolid. (N=2307) Body as a Whole Abdominal pain 6 4 Abscess 2 2 Asthenia 3 2 Headache 6 7 Infection 7 5 Cardiovascular System Phlebitis 3 4 Digestive System Diarrhea 12 11 Dyspepsia 2 2 Nausea 26 13 Vomiting 18 9 Hemic and Lymphatic System Anemia 5 6 Metabolic and Nutritional Alkaline Phosphatase Increased 3 3 Amylase Increased 3 2 Bilirubinemia 2 1 BUN Increased 3 1 Healing Abnormal 3 2 Hyponatremia 2 1 Hypoproteinemia 5 3 SGOT Increased LFT abnormalities in TYGACIL-treated patients were reported more frequently in the post therapy period than those in comparator-treated patients, which occurred more often on therapy. 4 5 SGPT Increased 5 5 Respiratory System Pneumonia 2 2 Nervous System Dizziness 3 3 Skin and Appendages Rash 3 4 In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, an adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between TYGACIL and comparator-treated patients (see Table 2 ). The cause of the imbalance has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities. Table 2. Patients with Outcome of Death by Infection Type TYGACIL Comparator Risk Difference The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. The 95% CI for each infection type was calculated using the normal approximation method without continuity correction. Infection Type n/N % n/N % % (95% CI) CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infections. Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis). cSSSI 12/834 1.4 6/813 0.7 0.7 (-0.3, 1.7) cIAI 42/1382 3.0 31/1393 2.2 0.8 (-0.4, 2.0) CAP 12/424 2.8 11/422 2.6 0.2 (-2.0, 2.4) HAP 66/467 14.1 57/467 12.2 1.9 (-2.4, 6.3) Non-VAP These are subgroups of the HAP population. 41/336 12.2 42/345 12.2 0.0 (-4.9, 4.9) VAP 25/131 19.1 15/122 12.3 6.8 (-2.1, 15.7) RP 11/128 8.6 2/43 4.7 3.9 (-4.0, 11.9) DFI 7/553 1.3 3/508 0.6 0.7 (-0.5, 1.8) Overall Adjusted 150/3788 4.0 110/3646 3.0 0.6 (0.1, 1.2) Overall adjusted (random effects model by trial weight) risk difference estimate and 95% CI. An analysis of mortality in all trials conducted for approved indications – cSSSI, cIAI, and CABP, including post-market trials (one in cSSSI and two in cIAI) – showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2). In comparative clinical studies, infection-related serious adverse reactions were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse reactions of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established [see Warnings and Precautions (5.10) ] . The most common adverse reactions were nausea and vomiting which generally occurred during the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with TYGACIL and comparators were either mild or moderate in severity. In patients treated with TYGACIL, nausea incidence was 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe). In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL and 6% for levofloxacin. Discontinuation from TYGACIL was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%). The following adverse reactions were reported (<2%) in patients receiving TYGACIL in clinical studies: Body as a Whole : injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis Cardiovascular System : thrombophlebitis Digestive System : anorexia, jaundice, abnormal stools Metabolic/Nutritional System : increased creatinine, hypocalcemia, hypoglycemia Special Senses : taste perversion Hemic and Lymphatic System : prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia Skin and Appendages : pruritus Urogenital System : vaginal moniliasis, vaginitis, leukorrhea

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of TYGACIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.

• anaphylactic reactions
• acute pancreatitis
• hepatic cholestasis, and jaundice
• severe skin reactions, including Stevens-Johnson Syndrome
• symptomatic hypoglycemia in patients with and without diabetes mellitus
• hypofibrinogenemia [see Warnings and Precautions (5.6) ]

• Warfarin : Suitable anticoagulation test should be monitored if TYGACIL is administered to patients receiving warfarin. ( 7.1 )
• Calcineurin Inhibitors : Serum concentrations of calcineurin inhibitors (e.g., tacrolimus, cyclosporine) should be monitored during treatment with TYGACIL due to risk of toxicity. ( 7.2 )

7.1 Warfarin Prothrombin time or other suitable anticoagulation test should be monitored if TYGACIL is administered with warfarin [see Clinical Pharmacology (12.3) ] .

7.2 Calcineurin Inhibitors Concomitant use of TYGACIL and calcineurin inhibitors such as tacrolimus or cyclosporine may lead to an increase in serum trough concentrations of the calcineurin inhibitors. Therefore, serum concentrations of the calcineurin inhibitor should be monitored during treatment with TYGACIL to avoid drug toxicity.

7.3 Oral Contraceptives Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective.

• Lactation : Avoid breastfeeding for longer than 3 weeks while taking TYGACIL. A lactating woman may also pump and discard breast milk during treatment and for 9 days after the last dose of TYGACIL ( 8.2 )
• Pediatrics : Use in patients under 18 years of age is not recommended. Pediatric trials were not conducted because of the higher risk of mortality seen in adult trials ( 8.4 )

8.1 Pregnancy Risk Summary TYGACIL, like other tetracycline class antibacterial drugs, may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.7 , 5.8) , Data , and Use in Specific Populations (8.4) ]. There are no available data on the risk of major birth defects or miscarriage following the use of TYGACIL during pregnancy. Administration of intravenous tigecycline in pregnant rats and rabbits during the period of organogenesis was associated with reduction in fetal weights and an increased incidence of skeletal anomalies (delays in bone ossification) at exposures of 5 and 1 times the human exposure at the recommended clinical dose in rats and rabbits, respectively. Advise the patient of the potential risk to the fetus if TYGACIL is used during the second or third trimester. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U. S. general population, the estimated background risk in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data The use of tetracycline-class antibacterial drugs, that includes TYGACIL, during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of deciduous teeth. This adverse reaction is more common during long-term use of tetracyclines but has been observed following repeated short-term courses. TYGACIL may cause reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. Animal Data In embryo-fetal development studies, tigecycline was administered during the period of organogenesis at doses up to 12 mg/kg/day in rats and 4 mg/kg in rabbits or 5 and 1 times the systemic exposure at the recommended clinical dose, respectively. In the rat study, decreased fetal weight and fetal skeletal variations (reduced ossification of the pubic, ischial, and supraoccipital bones and increased incidences of rudimentary 14 th rib) were observed in the presence of maternal toxicity at 12 mg/kg/day (5 times the recommended clinical dose based on systemic exposure). In rabbits, decreased fetal weights were observed in the presence of maternal toxicity at 4 mg/kg (equivalent to the human exposure at the recommended clinical dose). In preclinical safety studies, 14 C-labeled tigecycline crossed the placenta and was found in fetal tissues.

8.2 Lactation Risk Summary There are no data on the presence of tigecycline in human milk; however, tetracycline-class antibacterial drugs are present in breast milk. It is not known whether tigecycline has an effect on the breastfed infant or on milk production. Tigecycline has low oral bioavailability; therefore, infant exposure is expected to be low. Tigecycline is present in rat milk with little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TYGACIL and any potential adverse effects on the breastfed child from TYGACIL or from the underlying maternal condition (see Clinical Considerations ) . Clinical Considerations Because of the theoretical risk of dental discoloration and inhibition of bone growth, avoid breastfeeding if taking TYGACIL for longer than three weeks. A lactating woman may also consider interrupting breastfeeding and pumping and discarding breastmilk during administration of TYGACIL and for 9 days (approximately 5 half-lives) after the last dose in order to minimize drug exposure to a breastfed infant.

8.4 Pediatric Use Use in patients under 18 years of age is not recommended. Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Because of the increased mortality observed in TYGACIL-treated adult patients in clinical trials, pediatric trials of TYGACIL to evaluate the safety and efficacy of TYGACIL were not conducted. In situations where there are no other alternative antibacterial drugs, dosing has been proposed for pediatric patients 8 to 17 years of age based on data from pediatric pharmacokinetic studies [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] . Because of effects on tooth development, use in patients under 8 years of age is not recommended [see Warnings and Precautions (5.7) ] .

8.5 Geriatric Use Of the total number of subjects who received TYGACIL in Phase 3 clinical studies (n=2514), 664 were 65 and over, while 288 were 75 and over. No 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. No significant difference in tigecycline exposure was observed between healthy elderly subjects and younger subjects following a single 100 mg dose of tigecycline [see Clinical Pharmacology (12.3) ].

8.6 Hepatic Impairment No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). In patients with severe hepatic impairment (Child Pugh C), the initial dose of tigecycline should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response [see Clinical Pharmacology (12.3) and Dosage and Administration (2.2) ] .

Tigecycline is a tetracycline class antibacterial [see Microbiology (12.4) ].