Side Effects of Tygacil (tigecycline)

Tygacil (tigecycline) is an injectable antibiotic used to treat infections caused by susceptible bacteria. Tygacil is similar to tetracycline antibiotics and has activity against a large number of bacteria. 

Tygacil is an antibiotic used to treat:

• complicated skin infections caused by susceptable strains of bacteria,
• complicated intra-abdominal infections caused by susceptible strains of bacteria, and
• community-aquired bacterial pneumonia.

Tygacil binds to bacterial ribosomes which produce the cell's proteins. The binding prevents bacterial ribosomes from producing important proteins needed for bacterial growth and multiplication. Tygacil prevents bacteria from multiplying, but it does not kill bacteria. 

Common side effects of Tygacil include:

• diarrhea,
• nausea and
• vomiting.

Nausea and vomiting are mild or moderate and usually occur during the first two days of therapy.

Other side effects of Tygacil include:

• injection site reactions (pain, swelling, and irritation),
• increased or decreased heart rate,
• infections,
• increased sensitivity to sunlight, and
• permanent discoloration of teeth if used during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years).

Serious side effects of Tygacil include:

• alteration of normal bacteria in the colon that can lead to overgrowth of some bacteria such as Clostridium difficile, which causes inflammation of the colon (pseudomembranous colitis).
  • Signs of pseudomembranous colitis include diarrhea, fever, abdominal pain, and possibly shock.

Drug interactions of Tygacil include warfarin, because Tygacil may increase warfarin levels in blood which can increase the effects of warfarin and promote bleeding. 

Administration of Tygacil to pregnant women may harm a fetus, and use during tooth development may cause permanent discoloration of teeth. 

Use of Tygacil in nursing women has not been adequately studied. It is unknown if Tygacil is excreted in human breast milk. Consult your doctor before breastfeeding.

The most common side effects of tigecycline are diarrhea, nausea and vomiting. Nausea and vomiting is mild or moderate and usually occurs during the first two days of therapy.

Other side effects include:

• pain at the injection site;
• swelling and irritation;
• increased or decreased heart rate; and
• infections.

Tigecycline is similar to tetracycline antibiotics and therefore may have similar side effects such as increased sensitivity to sunlight. Tigecycline may cause permanent discoloration of teeth if used during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years).

Like other antibiotics, tygecycline can alter normal bacteria in the colon and encourage overgrowth of some bacteria such as Clostridium difficile, which causes inflammation of the colon (pseudomembranous colitis). Patients who develop signs of pseudomembranous colitis after starting tigecycline (diarrhea, fever, abdominal pain, and possibly shock) should contact their physician immediately.

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

• All-Cause Mortality
• Mortality Imbalance and Lower Cure Rates in Hospital-Acquired Pneumonia
• Anaphylaxis
• Hepatic Adverse Effects
• Pancreatitis

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, 2514 patients were treated with Tygacil. Tygacil was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of adverse reactions through test of cure reported in ≥2% of patients in these trials.

Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reportedin≥ 2% of Patients Treated in Clinical Studies

In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving Tygacil and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, an adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between Tygacil and comparator-treated patients (see Table 2). The cause of the imbalance has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities.

Table 2. Patients with Outcome of Death by Infection Type

An analysis of mortality in all trials conducted for approved indications -cSSSI, cIAI, and CABP, including post-market trials (one in cSSSI and two in cIAI) -showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2).

In comparative clinical studies, infection-related serious adverse reactions were more frequently reported for subjects treated with Tygacil (7%) versus comparators (6%). Serious adverse reactions of sepsis/septic shock were more frequently reported for subjects treated with Tygacil (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established.

The most common adverse reactions were nausea and vomiting which generally occurred during the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with Tygacil and comparators were either mild or moderate in severity. In patients treated with Tygacil, nausea incidence was 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe).

In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for Tygacil and 9% for vancomycin/aztreonam; vomiting incidence was 20% for Tygacil and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for Tygacil and 21% for imipenem/cilastatin; vomiting incidence was 20% for Tygacil and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for Tygacil and 8% for levofloxacin; vomiting incidence was 16% for Tygacil and 6% for levofloxacin.

Discontinuation from Tygacil was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%).

The following adverse reactions were reported (<2%) in patients receiving Tygacil in clinical studies:

Body as a Whole: injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis

Cardiovascular System: thrombophlebitis

Digestive System: anorexia, jaundice, abnormal stools

Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia

Special Senses: taste perversion

Hemic and Lymphatic System: prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia

Skin and Appendages: pruritus

Urogenital System: vaginal moniliasis, vaginitis, leukorrhea

Post-Marketing Experience

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

• anaphylactic reactions
• acute pancreatitis
• hepatic cholestasis, and jaundice
• severe skin reactions, including Stevens-Johnson Syndrome
• symptomatic hypoglycemia in patients with and without diabetes mellitus

Warfarin

Prothrombin time or other suitable anticoagulation test should be monitored if Tygacil is administered with warfarin.

Oral Contraceptives

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