tigecycline

REMS

Complicated skin/skin structure infections, complicated intra-abdominal infections, or community-acquired bacterial pneumonia caused by susceptible bacteria (should only be used when alternative treatments are not suitable; should NOT be used for diabetic foot infections).

Action ⬆ ⬇

Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.

Therapeutic effects:

Resolution of infection.

Spectrum:

Active against the following gram-positive bacteria: Enterococcus faecalis(vancomycin-susceptible strains only), Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains), Streptococcus agalactiae, Streptococcus anginosus, Streptococcus pneumoniae (penicillin-susceptible isolates), and Streptococcus pyogenes.
Also active against these gram-negative organisms: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Legionella pneumophila, Klebsiella oxytoca, and Klebsiella pneumoniae.
Additionally active against the following anaerobes: Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed with good penetration into gall bladder, lung, and colon.

Metabolism/Excretion: Minimal metabolism; primary route of elimination is biliary/fecal excretion of unchanged drug and metabolites (59%), 33% renal (22% unchanged).

Half-Life: 27.1 hr (after 1 dose); 42.4 hr after multiple doses.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Diabetic foot infections;
Hospital-acquired or ventilator-associated pneumonia;
Pedi: Children.

Use Cautiously in:

Complicated intra-abdominal infections due to perforation;
Severe hepatic impairment (↓ maintenance dose recommended);
OB: Use during pregnancy only if potential maternal benefit outweighs potential fetal risk; may cause permanent teeth discoloration and suppress bone growth in fetus, especially when used during 2nd or 3rd trimester
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Geri: Older adults may be more sensitive to adverse effects.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: STEVENS-JOHNSON SYNDROME (SJS)

Endo: hyperglycemia, hypoglycemia

F and E: hypocalcemia, hyponatremia

GI: nausea, vomiting, ↑liver enzymes, anorexia, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), dry mouth, jaundice, PANCREATITIS

GU: ↑serum creatinine

Hemat: hypofibrinogenemia

Local: injection site reactions

Neuro: dysgeusia, somnolence

Resp: pneumonia

Misc: DEATH, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

May ↓ the effectiveness of hormonal contraceptives.
Effects on warfarin are unknown; monitoring recommended.
May ↑ trough levels and risk of toxicity of calcineurin inhibitors, including cyclosporine and tacrolimus.

Route/Dosage ⬆ ⬇

IV (Adults ): 100 mg initially, then 50 mg every 12 hr for 5–14 days (skin/skin structure infections and intra-abdominal infections) or 7–14 days (pneumonia).

Hepatic Impairment

IV (Adults ): Severe hepatic impairment: 100 mg initially, then 25 mg every 12 hr.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 50 mg/vial

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity before initiating therapy. 1st dose may be given before receiving results.
Before initiating therapy, obtain a history of tetracycline hypersensitivity; may also have an allergic response to tigecycline.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Assess patient for signs of pancreatitis (nausea, vomiting, abdominal pain, increased serum lipase or amylase) periodically during therapy. May require discontinuation of therapy.
Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.

Lab Test Considerations:

Monitor baseline blood coagulation parameters, including fibrinogen, before starting therapy and regularly during therapy.May cause anemia, leukocytosis, and thrombocythemia.
- May cause ↑ serum alkaline phosphatase, amylase, bilirubin, LDH, AST, and ALT.
- May cause hyperglycemia, hypokalemia, hypoproteinemia, hypocalcemia, hyponatremia, and ↑ BUN.

Implementation ⬆ ⬇

May cause yellow-brown discoloration and softening of teeth and bones if administered prenatally or during early childhood. Not recommended for children under 8 yr of age or during pregnancy or lactation unless used for the treatment of anthrax.

IV Administration:

Intermittent Infusion: Reconstitute each vial with 5.3 mL of 0.9% NaCl or D5W to achieve a concentration of 10 mg/mL. Diluent: Dilute further in 100 mL of D5W, LR, or 0.9% NaCl. Reconstituted solution should be yellow to orange in color. Do not administer solutions that are discolored or contain particulate matter. Infusion is stable for up to 24 hr at room temperature or for up to 48 hr if refrigerated.Concentration: Final concentration of infusion should be 1 mg/mL.
Rate: Infuse over 30–60 min. Flush line before and after infusion with 0.9% NaCl or D5W.

Patient/Family Teaching ⬆ ⬇

Advise patient that full course of therapy should be completed, even if feeling better. Skipping doses or not completing full course of therapy may result in decreased effectiveness and increased risk of bacterial resistance.
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools). Skin rash, pruritus, and urticaria should also be reported.
Rep: Advise females of reproductive potential to use a nonhormonal method of contraception while taking tigecycline and until next menstrual period. Use during the second and third trimesters may cause permanent yellow-gray-brown discoloration of the teeth and reversible inhibition of bone growth. Advise patient to avoid breastfeeding during and for 9 days after last dose of tigecycline. Advise patient to notify health care professional if pregnancy is planned or suspected.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇