Semi-Synthetic Glycylcycline Antibiotics
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.Intravenous Administration
For a 50 mg dose, reconstitute 1 vial; and for a 100 mg dose, reconstitute 2 vials.
Reconstitute each vial with 5.3 mL of 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection to achieve a concentration of 10 mg/mL of tigecycline. NOTE: Each vial contains a 6% overage, and 5 mL of reconstituted solution is equivalent to 50 mg of the drug.
Gently swirl the vial until the drug dissolves.
Reconstituted solutions must be further diluted for IV infusion.
Withdraw 5 mL of the reconstituted solution from the vial and add to a 100 mL IV bag for infusion. The maximum concentration in the IV bag should be 1 mg/mL. The final solution should be yellow to orange in color; if it is not, discard the solution.
Storage: The diluted solution may be stored at room temperature (not to exceed 25 degrees C or 77 degrees F) for up to 24 hours (up to 6 hours reconstituted in the vial and the remaining time diluted for administration in the IV bag); if storage temperature exceeds 25 degrees C (77 degrees F), the reconstituted solution must be used immediately. Alternatively, reconstituted solution diluted with either 0.9% Sodium Chloride Injection or 5% Dextrose Injection may be refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to 48 hours in the IV bag.
Administer over 30 to 60 minutes through a dedicated line or a Y-site. If the same IV line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of tigecycline with an infusion solution compatible with tigecycline and with any other drug(s) administered via this common line, such as 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection.
azotemia / Delayed / 3.0-3.0
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
hepatic failure / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / 3.0-5.0
anemia / Delayed / 5.0-5.0
hyperamylasemia / Delayed / 3.0-3.0
phlebitis / Rapid / 3.0-3.0
impaired wound healing / Delayed / 3.0-3.0
hyperbilirubinemia / Delayed / 2.0-2.0
jaundice / Delayed / 0-2.0
candidiasis / Delayed / 0-2.0
vaginitis / Delayed / 0-2.0
eosinophilia / Delayed / 0-2.0
thrombocytopenia / Delayed / 0-2.0
edema / Delayed / 0-2.0
hyponatremia / Delayed / 2.0-2.0
hypocalcemia / Delayed / 0-2.0
hypoglycemia / Early / 0-2.0
cholestasis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
hypofibrinogenemia / Delayed / Incidence not known
enamel hypoplasia / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
nausea / Early / 26.0-26.0
vomiting / Early / 18.0-18.0
diarrhea / Early / 12.0-12.0
infection / Delayed / 0-7.0
abdominal pain / Early / 6.0-6.0
headache / Early / 6.0-6.0
dizziness / Early / 3.0-3.0
rash / Early / 3.0-3.0
asthenia / Delayed / 3.0-3.0
dysgeusia / Early / 0-2.0
anorexia / Delayed / 0-2.0
dyspepsia / Early / 2.0-2.0
pruritus / Rapid / 0-2.0
leukorrhea / Delayed / 0-2.0
injection site reaction / Rapid / 0-2.0
chills / Rapid / 0-2.0
photosensitivity / Delayed / Incidence not known
tooth discoloration / Delayed / Incidence not known
Tigecycline is FDA approved for treatment of complicated skin/skin structure infections, complicated intraabdominal infections, and community-acquired pneumonia; however because of a potential for increased mortality, the drug should be reserved for use when alternative treatment options are not suitable. An evaluation of pooled data from 10 clinical trials (for approved indications) found the adjusted mortality rate for tigecycline recipients to be 2.5% (66/2640) compared to 1.8% (48/2628) for patients receiving a comparator; the adjusted risk difference for mortality was 0.6% (95% CI 0.0, 1.2). These results were similar to a previously conducted meta-analysis of thirteen Phase 3 and 4 clinical trials (for approved and non-approved indications). In these trials, death occurred in 4% (150/3788) of patients receiving tigecycline and 3% (110/3646) of patients receiving comparator agents with an adjusted risk difference for all-cause mortality of 0.6% (95% CI 0.1, 1.2). The incidence of death by infection type was reported for the Phase 3 and 4 trials; the incidence appears to be highest for hospital-acquired pneumonia (especially ventilator-associated pneumonia), complicated skin and skin structure infections, complicated intra-abdominal infections, and diabetic foot infections. It should be noted that tigecycline is not FDA approved to treat a diabetic foot infection or a respiratory infection other than community acquired pneumonia (including hospital-acquired/ventilator-associated pneumonia). The incidence of death in patients treated with tigecycline as compared to those treated with comparator antibiotics (with respective risk difference and 95% confidence interval) include: 1.4% vs 0.7% in complicated skin and skin structure infection (0.7, -0.3 to 1.7), 3% vs 2.2% in complicated intra-abdominal infection (0.8, -0.4 to 2), 2.8% vs 2.6% in community-acquired pneumonia (0.2, -2 to 2.4), 14.1% vs 12.2% in hospital-acquired pneumonia (1.9, -2.4 to 6.3), 8.6% vs 4.7% in resistant pathogen infection (3.9, -4 to 11.9), and 1.3% vs 0.6% in diabetic foot infection (0.7, -0.5 to 1.8). Hospital-acquired pneumonia was further delineated into non-ventilator-associated pneumonia, which had a 12.2% incidence of death regardless of treatment, and ventilator-associated pneumonia, which had an incidence of death of 19.1% among patients treated with tigecycline and 12.3% among patients treated with comparator antibiotics, which equates to a risk difference of 6.8 (95% CI -2.1, 15.7). The cause for the difference in mortality has not been established; however, progression of infection, infection complications, and underlying co-morbidities are suspected. In addition to increased mortality risk, tigecycline has also failed to demonstrate efficacy when used to treat patients with a diabetic foot infection or hospital-acquired pneumonia. In one trial, a sub-group analysis of clinically evaluable patients with ventilator-associated pneumonia (VAP) found lower cure rates with tigecycline (47.9%) than with a comparator (70.1%). In another trial, use of tigecycline to treat diabetic foot infections failed to demonstrate non-inferiority.
Some formulations of tigecycline contain maltose, and use may result in laboratory test interference, specifically falsely elevated glucose readings leading to unrecognized hypoglycemia or inappropriate insulin administration. When administering tigecycline formulations that contain maltose to patients with diabetes mellitus, use glucose testing methods which do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase. Do not use blood glucose monitors or strips using glucose dehydrogenase pyrroloquinolinequinone (GDH-PGG), glucose-dye-oxidoreductase (GDO), or some glucose dehydrogenase flavin-adenine (GDH-FAD)-based methods because the presence of maltose can interfere with their readings.
Common Brand Names
IV glycylcycline antibiotic developed to circumvent resistance mechanisms. Spectrum similar to tetracycline, doxycycline, and minocycline, but has activity against tetracycline-resistant organisms. Used for complicated skin and skin structure infections, complicated intra-abdominal infections, and CAP.
Dosage And Indications
NOTE: Not indicated for the treatment of diabetic foot infections. During a clinical trial, use of the drug for this indication did not achieve non-inferiority.
Intravenous dosage Adults
100 mg IV initially, then 50 mg IV every 12 hours. Infusions should be administered over 30 to 60 minutes. Overall duration of therapy in clinical trials ranged from 7 to 14 days; however, this may include a switch to appropriate oral therapy.
50 mg IV every 12 hours has been suggested based on pharmacokinetic studies; safety and efficacy of tigecycline have not been evaluated in pediatric clinical trials.
1.2 mg/kg/dose IV every 12 hours (Max: 50 mg/dose) has been suggested based on pharmacokinetic studies; safety and efficacy of tigecycline have not been evaluated in pediatric clinical trials.
100 mg IV initially, then 50 mg IV every 12 hours for 5 to 14 days. Avoid monotherapy with tigecycline in patients with complicated intra-abdominal infections secondary to clinically apparent intestinal perforation.
50 mg IV every 12 hours has been suggested based on pharmacokinetic studies; safety and efficacy of tigecycline have not been evaluated in pediatric clinical trials. Avoid monotherapy with tigecycline in patients with complicated intra-abdominal infections secondary to clinically apparent intestinal perforation.
1.2 mg/kg/dose (Max: 50 mg/dose) IV every 12 hours has been suggested based on pharmacokinetic studies; safety and efficacy of tigecycline have not been evaluated in pediatric clinical trials. Avoid monotherapy with tigecycline in patients with complicated intraabdominal infections secondary to clinically apparent intestinal perforation.
100 mg IV initially, then 50 mg IV every 12 hours as monotherapy or as part of combination therapy for 3 to 7 days. Avoid monotherapy with tigecycline in patients with complicated intra-abdominal infections secondary to clinically apparent intestinal perforation. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
200 mg IV initially, then 100 mg IV every 12 hours as monotherapy or as part of combination therapy for 3 to 7 days. Avoid monotherapy with tigecycline in patients with complicated intra-abdominal infections secondary to clinically apparent intestinal perforation. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
100 mg IV initially, then 50 mg IV every 12 hours as monotherapy or as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
100 mg IV once, then 50 mg IV every 12 hours for 7 to 14 days.
50 mg IV every 12 hours.
1.2 mg/kg/dose (Max: 50 mg/dose) IV every 12 hours.
100 mg IV once, then 50 mg IV every 12 hours has been studied. Guidelines suggest the early use of tigecycline when Klebsiella pneumoniae carbapenamses (KPCs) may be a factor. Use only in combination with other antipseudomonal antibiotics.
100 mg IV initially, then 50 mg IV every 12 hours as add-on therapy to standard treatment.
100 mg IV initially, then 50 mg IV every 12 hours plus rectal vancomycin.
†Indicates off-label use
In patients with severe hepatic impairment (Child-Pugh Class C), reduce the maintenance dose to 25 mg IV every 12 hours after the initial 100 mg IV dose. No dosage adjustments are required in patients with mild or moderate hepatic impairment (Child-Pugh Class A and B).Renal Impairment
No dosage adjustment is needed in patients with renal impairment.
Tigecycline is not removed by hemodialysis. No dosage adjustment is needed.
No dosage adjustment is needed.
Continuous renal replacement therapy (CRRT)†
No dosage adjustment is needed.
Cyclosporine: (Moderate) Monitor cyclosporine serum trough concentrations during treatment with tigecycline to avoid cyclosporine toxicity. Concomitant use of cyclosporine and tigecycline may lead to an increase in serum trough concentrations of cyclosporine.
Dichlorphenamide: (Moderate) Use dichlorphenamide and tigecycline together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Estradiol: (Moderate) The manufacturer of tigecycline reports that concurrent use of antibacterial drugs with oral contraceptives may decrease the efficacy of oral contraceptives. However, the effect of tigecycline specifically on the efficacy of oral contraceptives is unknown. Alternative or additional contraception may be advisable.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Tacrolimus: (Moderate) Monitor tacrolimus serum trough concentrations during treatment with tigecycline to avoid tacrolimus toxicity. Concomitant use of tacrolimus and tigecycline may lead to an increase in serum trough concentrations of tacrolimus.
Warfarin: (Moderate) In healthy subjects receiving tigecycline (repeated dosing) and warfarin (25 mg single dose) concomitantly, the clearance of R-warfarin and S-warfarin was decreased by 40% and 23%, the Cmax increased by 38% and 43%, and the AUC increased by 68% and 29%, respectively. Tigecycline did not significantly alter the effects of warfarin on the INR in this single-dose study. Warfarin did not affect the pharmacokinetic profile of tigecycline. However, it is recommended that the prothrombin time or other suitable anticoagulation test (i.e., INR) be monitored if tigecycline is administered with warfarin.
Tigecycline/Tygacil Intravenous Inj Pwd F/Sol: 50mg
100 mg/day IV; a 100 mg loading dose followed by 50 mg IV 12 hours later is given on day 1.Geriatric
100 mg/day IV; a 100 mg loading dose followed by 50 mg IV 12 hours later is given on day 1.Adolescents
Safety and efficacy have not been established; however, 50 mg IV every 12 hours has been suggested based on pharmacokinetic studies.Children
12 years and older: Safety and efficacy have not been established; however, 50 mg IV every 12 hours has been suggested based on pharmacokinetic studies.
8 to 11 years: Safety and efficacy have not been established; however, 1.2 mg/kg/dose (Max: 50 mg/dose) every 12 hours has been suggested based on pharmacokinetic studies.
1 to 7 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.Neonates
Safety and efficacy have not been established.
Mechanism Of Action
Generally, tigecycline is a bacteriostatic agent. Tigecycline, as a tetracycline class antibacterial, binds to the 30S ribosomal subunit of susceptible organisms. This prevents binding of tRNA to the mRNA-ribosome complex, thus interfering with protein synthesis. Tigecycline binds 5-times more strongly to the ribosome compared to tetracycline or minocycline. Tigecycline is less affected by tetracycline-resistant organisms exhibiting genes for efflux and ribosomal resistance mechanisms, the 2 major tetracycline resistance mechanisms. Other resistance mechanisms such as beta-lactamases (including extended-spectrum beta-lactamases), target site modifications, macrolide efflux pumps or enzyme target changes (e.g., gyrase/topoisomerase) do not affect the activity of tigecycline. In vitro studies have not shown antagonism between tigecycline and other commonly used antimicrobial agents.  
Tigecycline exhibits concentration-independent killing in which there is saturation of the bacterial killing rate once the drug concentrations approach the minimum inhibitory concentration (MIC). Pharmacodynamic models suggest that the pharmacokinetic-pharmacodynamic parameter that correlates best with in vivo tigecycline activity is the 24-hour area under the curve to MIC ratio (AUC:MIC), also known as area-under-the-inhibitory curve (AUIC). Animal models showed that the AUC:MIC necessary for bacteriostatic activity was about 20; however, the presence of neutrophils may reduce that value to 5 to 10 due to the higher tigecycline concentrations present in neutrophils. Tigecycline also has a prolonged post-antibiotic effect (PAE) where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The PAE can be bacteria-specific, as well as drug-specific. The in vivo PAE of tigecycline was found to be 8.9 hours against S. pneumoniae and 4.9 hours against E. coli.  
The spectrum of activity of tigecycline includes gram-positive, gram-negative, atypical, and anaerobic microorganisms. Notable activity against gram-positive organisms includes S. aureus (including MRSA), penicillin-resistant S. pneumoniae, and vancomycin-resistant enterococci (VRE). Tigecycline has activity against a wide variety of Enterobacteriaceae, including extended-spectrum beta-lactamase (ESBL) producing E. coli and Klebsiella sp.; however, there is decreased in vitro activity against Morganella sp., Proteus sp., and Providencia sp. In general, tigecycline has limited activity against Pseudomonas aeruginosa. There is good activity against atypical pathogens, including L. pneumophila and several Mycobacterium sp.   In a review of tigecycline, the in vitro activities of tigecycline, doxycycline, minocycline, and tetracycline against some clinically relevant bacteria were compared. Against methicillin-susceptible Staphylococcus aureus (MSSA), tigecycline was less active than minocycline, comparable to doxycycline, and more active than tetracycline; however, against resistant strains, tigecycline was the most active. For Streptococcus sp., tigecycline has better activity against S. pyogenes and S. agalactiae. Tigecycline also shows significantly greater activity against penicillin-susceptible, -intermediate and -resistant strains of Streptococcus pneumoniae. The activity of tigecycline is similar to that of the tetracyclines for the gram-negative aerobes. However, tigecycline has improved activity against Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella sp., Salmonella sp., Serratia marcescens, and Shigella sp. Tigecycline is less active against Burkholderia cepacia than minocycline and tetracycline and less active than minocycline against Stenotrophomonas maltophilia. In regards to gram-negative anaerobic bacteria, tigecycline has improved activity against Bacteroides fragilis but similar activity against B. fragilis group compared to minocycline and doxycycline. Tigecycline also shows greater activity against Peptostreptococcus sp. than other tetracyclines. Tigecycline has similar activity to doxycycline against Chlamydia pneumoniae but has improved activity against Mycoplasma pneumoniae compared to tetracycline and doxycycline.
Susceptibilities for tigecycline are delineated by pathogen. For S. aureus (including MRSA), MICs of 0.5 mcg/mL or less are susceptible. For Streptococcus sp. (other than S. pneumoniae), E. faecalis (vancomycin-susceptible strains), and H. influenzae, MICs of 0.25 mcg/mL or less are susceptible. For S. pneumoniae, MICs of 0.06 mcg/mL or less are susceptible. For the other Enterobacteriaceae, breakpoints of 2 mcg/mL or less are susceptible, 4 mcg/mL is intermediate, and 8 mcg/mL or more are resistant. For anaerobes, MICs of 4 mcg/mL or less are susceptible, 8 mcg/mL is intermediate, and 16 mcg/mL or more are considered resistant.
Due to increased binding, tigecycline is not subject to many efflux mechanisms that affect the tetracycline class; however, tigecycline is susceptible to certain constitutively overexpressed multidrug efflux pumps, which may explain some of the reduced susceptibility of Morganella sp., Proteus sp., and Providencia sp. Additionally, there have been reports of modification of tigecycline by the TetX protein (enzymatic modification), which may impair the ability of tigecycline to inhibit bacterial protein translation. 
Tigecycline is administered intravenously as an infusion. Based on clinical studies, the in vitro plasma protein binding ranges from approximately 71% to 89%. It is distributed extensively throughout the body into the tissues; the steady-state volume of distribution averaged 500 to 700 L (7 to 9 L/kg). In a single-dose study, 100 mg IV was given to patients prior to undergoing elective surgery or medical procedure for tissue extraction. Concentrations at 4 hours after administration were higher in gallbladder, lung, and colon, and lower in synovial fluid, and bone relative to serum. Concentrations in these tissues after multiple doses has not been studied.
Tigecycline is not extensively metabolized. Based on in vitro data from studies of human liver microsomes, liver slices, and hepatocytes, only trace amounts of metabolites were identified. In healthy male volunteers receiving 14C-tigecycline, tigecycline was the primary 14C-labeled material found in urine and feces, however, a glucuronide, a N-acetyl metabolite, and a tigecycline epimer were also identified at no more than 10% of the administered dose. The radiolabeled study also indicates that 59% of an administered dose is eliminated by biliary/fecal excretion, and 33% is excreted in urine. Approximately 22% of an administered dose is excreted unchanged in the urine. The primary route of elimination is via biliary excretion of unchanged drug and its metabolites. Glucuronidation and renal excretion of unchanged drug are secondary routes. The mean elimination half-life ranges from about 27 hours following a single 100 mg dose to 42 hours after multiple doses.
Affected cytochrome P450 isoenzymes and drug transporters: P-gp
Based on data from in vitro studies in human liver microsomes, tigecycline does not inhibit metabolism mediated by any of the following cytochrome P450 (CYP) enzymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Therefore, it is not expected to alter the metabolism of drugs metabolized by these enzymes. Additionally, because it is not extensively metabolized, clearance is not expected to be affected by drugs that inhibit or induce the activity of these CYP450 enzymes. Based on an in vitro study, tigecycline is a P-glycoprotein (P-gp) substrate; however, the potential contribution of P-gp-mediated transport to the in vivo disposition of tigecycline is not known. Tigecycline does not inhibit P-gp.
After IV administration, peak plasma concentrations (Cmax) of tigecycline following 30-minute infusions range from 1.4 mcg/mL for a single 100 mg dose to 0.87 mcg/mL for multiple doses (100 mg initially, followed by 50 mg ever 12 hours). After a 60-minute infusion, Cmax ranges from 0.9 mcg/mL after a single dose to 0.63 mcg/mL after multiple doses. After administration of a standard regimen of tigecycline to healthy volunteers, the tigecycline AUC0 - 12h in alveolar cells was approximately 78-fold higher than the AUC0 - 12h in serum. The AUC0 - 12h in epithelial lining fluid was approximately 32% higher than the AUC0 - 12h in serum. In skin blister fluid, the AUC0 - 12h was about 26% lower than the AUC0 - 12h in the serum.
Pregnancy And Lactation
There are no available data on the risk of major birth defects of miscarriage after tigecycline use during pregnancy. Tetracyclines may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy. Tooth discoloration is more common during long-term use of tetracyclines but has been observed after repeated short-term courses. Advise the patient of the potential risk to the fetus if tigecycline is used during pregnancy. Results of animal studies show that tigecycline crosses the placenta and is found in fetal tissues, including fetal bony structures. Decreased fetal weights and an increased incidence of skeletal anomalies (with associated delays in ossification) were observed in animals at tigecycline exposures of 5 and 1 times the human exposure at the recommended clinical dose.  
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 tetracycline has an effect on the breast-fed infant or on milk production. Tigecycline has low oral bioavailability; therefore, infant exposure is expected to be low. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tigecycline and any potential adverse effects on the breast-fed child from tigecycline or the mother's underlying medical condition. Due to the theoretical risk of tooth discoloration and bone growth inhibition, avoid breast-feeding if taking tigecycline for longer than 3 weeks. A lactating woman may consider interrupting breast-feeding and pumping and discarding breast milk during tigecycline use and for 9 days (approximately 5 half-lives) after the last dose in order to minimize drug exposure to the breast-fed infant. Tigecycline is readily excreted in the milk of lactating rats, but there was little or no systemic exposure 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.  Vancomycin, daptomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. Assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal.  Daptomycin has a high molecular weight; therefore, excretion into breast milk may be limited. In 1 patient with daptomycin breast milk concentration measured on day 27 of therapy (dose of 6.7 mg/kg IV), a peak concentration of 44.7 mcg/L was obtained 8 hours after the dose with an estimated milk:plasma ratio of 0.0012. Alternative antimicrobials that previous American Academy of Pediatrics recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.