Tigecycline is an intravenous glycylcycline antibiotic for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections. It is a derivative of minocycline and was developed to circumvent resistance mechanisms. The spectrum of activity of tigecycline is similar to that of tetracycline, doxycycline, and minocycline; however, tigecycline shows activity against tetracycline-resistant organisms. Tigecycline has activity against methicillin-resistant Staphylococcus aureus (MRSA) and S. epidermidis (MRSE), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). There have been no reports of cross-resistance between tigecycline and other antibiotics. Tigecycline has also shown activity against multi-drug resistant organisms. Tigecycline and other glycylcycline antibiotics are associated with adverse reactions and drug interactions similar to the tetracyclines. Tigecycline failed to demonstrate efficacy in patients with hospital acquired pneumonia, and a sub-group of patients with ventilator-associated pneumonia (VAP) had lower cure rates and higher mortality than the comparator group. The FDA approved tigecycline in June 2005 for complicated intra-abdominal infections and complicated skin and skin structure infections due to gram-negative and gram-positive organisms, anaerobes, and both MSSA and MRSA. In March 2009, the FDA approved tigecycline for community-acquired pneumonia (CAP).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution:
-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.
Intravenous infusion:
-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.
An increase in all-cause mortality has been observed across Phase 3 and 4 clinical trials in tigecycline-treated patients versus comparator-treated patients. Death occurred in 4% (150/3788) of patients receiving tigecycline and 3% (110/3646) of patients receiving comparator agents with an adjusted risk difference of all-cause mortality of 0.6% (95% CI 0.1, 1.2) between tigecycline and comparator-treated patients. Also, a study of hospital acquired pneumonia patients failed to demonstrate efficacy. Further, in this study, a sub-group of tigecycline-treated patients with ventilator-associated pneumonia (VAP) had lower cure rates (47.9% versus 70.1% for the clinically evaluable population) and a higher mortality (25/131, 19.1% vs. 15/122, 12.3%) than the comparator group. Particularly high mortality was noted among tigecycline-treated patients with ventilator-associated pneumonia and bacteremia at baseline (9/18, 50%) versus comparator-treated patients (1/13, 7.7%).The cause of this increase has not been established.
The most frequently reported adverse reactions during clinical trials of tigecycline included nausea (26%) and vomiting (18%) and generally occurred during the first 1-2 days of treatment. Most cases of nausea and vomiting were mild or moderate in severity. Other gastrointestinal adverse events included abdominal pain (6%), diarrhea (12%), and dyspepsia (2%). Anorexia, abnormal stools, and taste perversion (dysgeusia) were reported in <2% of patients.
Central nervous system adverse events reported in tigecycline clinical trials include headache (6%) and dizziness (3%).
Allergic reaction to tigecycline was reported in < 2% of patients during clinical trials. Anaphylaxis, anaphylactoid reactions, and anaphylactic shock have been noted in post-marketing reports for tigecycline and may be life-threatening.
There have been isolated cases of significant hepatic dysfunction and hepatic failure in patients receiving tigecycline. Often these patients were receiving multiple medications. Elevated hepatic enzymes have been reported during tigecycline clinical trials. Elevated SGOT occurred in 4% of patients and elevated SGPT occurred in 5% of patients. Increased alkaline phosphatase was reported in 3% of patients, while hyperbilirubinemia occurred in 2% of patients. Jaundice has been reported in < 2% of patients in trials. Hepatic cholestasis has been noted in post-marketing reports. Patients who develop abnormal liver functions tests while being treated with tigecycline should be monitored for worsening hepatic function.
Rash (unspecified) has been reported in 3% of patients during tigecycline clinical trials, while pruritus has been reported in < 2% of patients. Severe skin reactions, including Stevens-Johnson syndrome have been noted in post-marketing reports.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with tigecycline. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other infection-related serious adverse events were reported in tigecycline patients (7%) and include abscess (2%), infection (7%), pneumonia (2%), septic shock (2% or less), vaginitis (less than 2%), vaginal moniliasis (candidiasis) (less than 2%), and leukorrhea (less than 2%).
Increased BUN (azotemia) was reported in 3% of patients and increased creatinine was reported in < 2% of patients during tigecycline clinical trials.
Glycylcycline antibiotics such as tigecycline are structurally similar to tetracyclines and may have similar adverse effects. These effects may include photosensitivity, pseudotumor cerebri, and anti-anabolic actions (which has lead to increased BUN, azotemia, hypophosphatemia, and metabolic acidosis).
Acute pancreatitis, sometimes fatal, and hyperamylasemia (3%) have been reported. The diagnosis of pancreatitis should be considered in patients who develop signs, symptoms, or laboratory abnormalities suggestive of pancreatitis. Consideration should also be given to stopping tigecycline in these patients; patients usually improve after drug discontinuation.
Anemia was reported in 5% of patients in tigecycline clinical trials. Prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT), increased international normalized ratio (INR), thrombocytopenia, and eosinophilia were reported in less than 2% of patients. Hypofibrinogenemia has been reported in patients treated with tigecycline in postmarketing experience. Obtain baseline coagulation parameters, including fibrinogen, and monitor regularly during tigecycline treatment.
Asthenia was reported in 3% of patients during tigecycline clinical trials.
Phlebitis was reported in 3% of patients during tigecycline clinical trials. Thrombophlebitis, injection site reaction, injection site inflammation, injection site pain, injection site edema, and injection site phlebitis were all noted in < 2% of patients.
Abnormal or impaired wound healing was reported in 3% of patients during tigecycline clinical trials. Chills were reported in < 2% of patients in trials.
Hyponatremia has been reported in 2% of patients during tigecycline clinical trials. Hypocalcemia and hypoglycemia were reported in < 2% of patients during trials.
The use of tigecycline during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years old) may cause permanent tooth discoloration (yellow-gray-brown). This adverse reaction is more common during long-term use of tetracyclines, but it has been observed after repeated short-term courses. Enamel hypoplasia has also been reported.
Tigecycline may cause reversible bone growth inhibition in neonates, infants, and children younger than 8 years. 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 drug was discontinued.
Prescribing tigecycline in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. As with other antibiotics, tigecycline therapy can result in superinfection or suprainfection with non susceptible organisms, including fungi. Patients should be monitored closely during therapy. If superinfection occurs, appropriate measures should be taken.
Tigecycline is structurally similar to tetracyclines and may have similar adverse effects. Therefore, tigecycline should be avoided in patients with tigecycline hypersensitivity or known tetracyclines hypersensitivity.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including tigecycline, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Tigecycline should be used with caution in patients with severe hepatic disease (Child Pugh C); dosage adjustments are needed in these patients (see Dosage). Patients with mild to moderate hepatic disease (Child Pugh A and B) do not require dosage adjustments.
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.
Avoid tigecycline use in pediatric patients unless no alternative therapy is available. The use of tigecycline in the second and third trimesters of pregnancy, neonates, infants, and children up to the age of 8 years may cause permanent yellow-gray-brown discoloration of the teeth as well as reversible inhibition of bone growth. Enamel hypoplasia has also been reported. 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.
The manufacturer cautions against using tigecycline monotherapy in patients with complicated intra-abdominal infections secondary to clinically apparent GI perforation. In phase 3 studies (n=1642), 6 patients treated with tigecycline and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/shock. The 6 tigecycline patients had higher Acute Physiology and Chronic Health Status Evaluation (APACHE II) scores (median = 13) compared to the other 2 patients (APACHE II scores = 4 and 6). Due to differences in baseline APACHE II scores between the two groups and small overall numbers, the relationship of this outcome to treatment cannot be established.
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.
Approximately 27% of patients in phase 3 clinical trials of tigecycline (n = 1,415) were geriatric patients (age 65 years or over). No unexpected overall differences in safety or effectiveness were observed between geriatric and younger subjects during clinical trials. However, the greater sensitivity to adverse reactions of some older individuals cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
Acute pancreatitis, including fatal cases, has occurred in association with tigecycline treatment and has been reported in patients with no known risk factors for pancreatitis. Tigecycline should be discontinued in patients with signs and symptoms of acute pancreatitis. Patient improvement usually occurs after tigecycline discontinuation.
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.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, this drug should be used only to treat or prevent 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.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter baumannii, Aeromonas hydrophila, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Citrobacter koseri, Clostridium perfringens, Enterobacter cloacae, Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Legionella pneumophila, Listeria monocytogenes, Mycobacterium abscessus, Mycobacterium fortuitum, Parabacteroides distasonis, Pasteurella multocida, Peptostreptococcus micros, Peptostreptococcus sp., Porphyromonas sp., Prevotella sp., Serratia marcescens, Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Stenotrophomonas maltophilia, Streptococcus agalactiae (group B streptococci), Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Clostridioides difficile
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of complicated skin and skin structure infections caused by susceptible organisms when alternative treatment options are not suitable:
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.
Children and Adolescents 12 to 17 years*: 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.
Children 8 to 11 years*: 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.
For the treatment of intraabdominal infections, including peritonitis, appendicitis, and intraabdominal abscess, when alternative treatment options are not suitable:
-for the general treatment of complicated intraabdominal infections:
Intravenous dosage:
Adults: 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.
Children and Adolescents 12 to 17 years*: 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.
Children 8 to 11 years*: 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.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Adults: 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.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control due to resistant gram-negative organisms:
Intravenous dosage:
Adults: 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.
-for the treatment of uncomplicated intraabdominal infections*, including for the treatment of resistant gram-negative organisms:
Intravenous dosage:
Adults: 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.
For the treatment of community-acquired pneumonia (CAP) when alternative treatment options are not suitable:
Intravenous dosage:
Adults: 100 mg IV once, then 50 mg IV every 12 hours for 7 to 14 days.
Children and Adolescents 12 to 17 years*: 50 mg IV every 12 hours.
Children 8 to 11 years*: 1.2 mg/kg/dose (Max: 50 mg/dose) IV every 12 hours.
For the treatment of febrile neutropenia*:
Intravenous dosage:
Adults: 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.
For the treatment of of pseudomembranous colitis* due to C. difficile infection*:
-for the treatment of pseudomembranous colitis* due to C. difficile infection* in patients with progressing disease:
Intravenous dosage:
Adults: 100 mg IV initially, then 50 mg IV every 12 hours as add-on therapy to standard treatment.
-for the treatment of pseudomembranous colitis* due to C. difficile infection* when no oral treatment is possible:
Intravenous dosage:
Adults: 100 mg IV initially, then 50 mg IV every 12 hours plus rectal vancomycin.
Maximum Dosage Limits:
-Adults
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.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
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).
Patients with Renal Impairment Dosing
No dosage adjustment is needed in patients with renal impairment.
Intermittent hemodialysis
Tigecycline is not removed by hemodialysis. No dosage adjustment is needed.
Peritoneal dialysis*
No dosage adjustment is needed.
Continuous renal replacement therapy (CRRT)*
No dosage adjustment is needed.
*non-FDA-approved indication
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.
Desogestrel; Ethinyl Estradiol: (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.
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.
Dienogest; Estradiol valerate: (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.
Drospirenone: (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.
Drospirenone; Estetrol: (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.
Drospirenone; Estradiol: (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.
Drospirenone; Ethinyl Estradiol: (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.
Drospirenone; Ethinyl Estradiol; Levomefolate: (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.
Elagolix; Estradiol; Norethindrone acetate: (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.
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.
Estradiol; Levonorgestrel: (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.
Estradiol; Norethindrone: (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.
Estradiol; Norgestimate: (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.
Ethinyl Estradiol; Norelgestromin: (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.
Ethinyl Estradiol; Norethindrone Acetate: (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.
Ethinyl Estradiol; Norgestrel: (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.
Ethynodiol Diacetate; Ethinyl Estradiol: (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.
Etonogestrel; Ethinyl Estradiol: (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.
Leuprolide; Norethindrone: (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.
Levonorgestrel: (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.
Levonorgestrel; Ethinyl Estradiol: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (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.
Norethindrone: (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.
Norethindrone; Ethinyl Estradiol: (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.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (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.
Norgestimate; Ethinyl Estradiol: (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.
Norgestrel: (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.
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.
Relugolix; Estradiol; Norethindrone acetate: (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.
Segesterone Acetate; Ethinyl Estradiol: (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.
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.
-Route-Specific Pharmacokinetics
Intravenous Route
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.
-Special Populations
Hepatic Impairment
The pharmacokinetic parameters of tigecycline are not altered in patients with mild hepatic impairment (Child Pugh class A). However, tigecycline systemic clearance was reduced by 25% and half-life prolonged by 23% in patients with moderate hepatic impairment (Child Pugh class B). In patients with severe hepatic impairment (Child Pugh class C), systemic clearance of tigecycline was reduced by 55% and the half-life prolonged by 43%. Based on the pharmacokinetic profile of tigecycline, no dosage adjustment is recommended in patients with mild to moderate hepatic insufficiency; however, a reduction in the tigecycline maintenance dose is necessary in patients with severe hepatic dysfunction.
Renal Impairment
Renal impairment does not alter the pharmacokinetics of tigecycline; hemodialysis does not remove tigecycline. The effect of peritoneal dialysis on tigecycline pharmacokinetics has not been determined.
Pediatrics
In a single-dose pharmacokinetic study in 16 pediatric patients ages 12 to 16 years, a dose of 50 mg IV twice daily was shown to likely result in comparable exposures to those seen in adults. In another pharmacokinetic study in which pediatric patients 8 to 11 years received 0.75 mg/kg/dose (n = 17), 1 mg/kg/dose (n = 21), or 1.25 mg/kg/dose (n = 20), a dose of 1.2 mg/kg IV twice daily was shown to likely result in comparable exposures to those seen in adults.
Geriatric
In adults, tigecycline pharmacokinetics are not significantly influenced by advanced age.
Gender Differences
In adults, tigecycline pharmacokinetics are not significantly influenced by gender.
Ethnic Differences
In adults, tigecycline pharmacokinetics are not significantly influenced by race.