Tigacil

Tygacil is an antibiotic from the glycylcycline subgroup; its structure is similar to tetracycline antibiotics.

Contains the element tigecycline, which exhibits a broad spectrum of antibacterial activity. However, tigecycline has no protection against the bacterial resistance mechanism in the form of active cellular excretion, which is encoded by the chromosomes of Pseudomonas aeruginosa and Proteae. [ 1 ]

Tigecycline has no cross-resistance to most antibiotic subgroups.[ 2 ]

Indications Tigacil

It is used for therapy of complicated infections (in the subcutaneous layer with the epidermis, as well as in the intra-abdominal zone), and also for outpatient pneumonia.

Release form

The medicinal substance is released in the form of powder for infusion liquid, inside glass bottles with a volume of 5 ml. There are 10 such bottles inside the pack.

Pharmacodynamics

The drug slows down protein translation in microbes by synthesizing with the ribosomal 30S subunit, and also by blocking the passage of aminoacyl-tRNA molecules into the ribosomal A-site region, as a result of which amino acid residues are not included in the growing peptide chains.

Tigecycline is capable of demonstrating bacteriostatic activity. In the case of using a 4-fold MIC of the substance, a halving of the number of colonies of Staphylococcus aureus, enterococci and Escherichia coli was observed. [ 3 ]

A bactericidal effect is observed against Haemophilus influenzae, pneumococcus and Legionella pneumophila.

Pharmacokinetics

Absorption.

Since tigecycline is administered intravenously, it has 100% bioavailability.

Distribution processes.

When concentrations in the range of 0.1-1 μg/ml are used, the protein synthesis of tigecycline in vitro fluctuates in the range of approximately 71-89%. Pharmacokinetic tests in humans and animals have shown that the substance is distributed within tissues at a high rate.

Within the body, the equilibrium level of Vd of tigecycline is 500-700 L, from which it can be concluded that the substance is distributed extensively, outside the plasma, and also accumulates within tissues.

There is no information regarding the ability of the drug to cross the BBB.

Serum Cssmax values of tigecycline are 866±233 ng/mL in the case of a half-hour infusion, and 634±97 ng/mL in the case of a 1-hour infusion. The AUC value in the range of 0-12 hours is 2349±850 ng×hour/mL.

Exchange processes.

Less than 20% of the drug (on average) is involved in metabolic processes. The main element registered in feces and urine is unchanged tigecycline; in addition, tigecycline epimer, glucuronide and N-acetyl metabolic component are noted.

Tigecycline does not inhibit metabolic processes developing with the help of 6 isoenzymes (CYP1A2 and CYP2C8, as well as CYP2C9 with CYP2C19 and CYP2D6 together with CYP3A4). The substance does not exhibit competitive or irreversible inhibitory effect on hemoprotein P450.

Excretion.

It was found that 59% of the administered portion is excreted by the intestines (with the main part of the unchanged element being excreted in the bile), and another 33% through the kidneys. Additional excretion pathways include glucuronidation processes and renal excretion of the unchanged component.

Dosing and administration

The medication is administered intravenously through a drip over a period of 0.5-1 hour. The initial dosage is 0.1 g; subsequently, 0.05 g of the substance should be administered at 12-hour intervals.

The therapeutic cycle for complicated infections in the intra-abdominal zone or in the subcutaneous layer with the epidermis lasts 5-14 days; in the case of outpatient pneumonia – 1-2 weeks.

The duration of therapy is selected taking into account the localization of the infection and its severity, as well as the clinical response to the treatment.

• Application for children

There is no information regarding the safety and therapeutic efficacy of the drug when used in pediatrics (in individuals under 18 years of age).

Use Tigacil during pregnancy

Tygacil may be prescribed to pregnant women only under strict indications, when the expected benefit to the woman is more likely than the risk of complications to the fetus.

There is no information on whether tigecycline is excreted in breast milk. If the drug is prescribed during breastfeeding, breastfeeding should be discontinued for the duration of therapy.

Contraindications

Main contraindications:

• pronounced personal sensitivity to the components of the drug;
• severe intolerance to tetracycline antibiotics.

Caution is required when used in individuals with severe liver dysfunction.

Side effects Tigacil

Side effects include:

• disorders of blood coagulation function: often there is an increase in the values of PT/INR or APTT;
• problems with the functioning of the hematopoietic system: eosinophilia is sometimes observed. Thrombocytopenia is occasionally observed;
• manifestations of allergy: anaphylactoid/anaphylactic symptoms are observed occasionally;
• CNS disorders: dizziness often occurs;
• lesions affecting the cardiovascular system: phlebitis often develops. Sometimes thrombophlebitis appears;
• digestive dysfunction: vomiting, diarrhea and nausea occur in most cases. Abdominal pain, anorexia and dyspepsia often occur. Sometimes hyperbilirubinemia, active pancreatitis and jaundice occur, and the ALT and AST levels increase. Liver failure and severe liver dysfunctions occur occasionally;
• dermatological lesions: rashes and itching are often observed;
• problems with sexual function: sometimes thrush, leukorrhea or vaginitis occur;
• local signs: sometimes pain, phlebitis, inflammation or swelling in the injection area are noted;
• Others: asthenia or headache often occurs and wound healing is slowed. Chills are sometimes observed;
• changes in test results: hypoproteinemia often develops or serum alkaline phosphatase, blood urea nitrogen, and serum amylase levels increase. Sometimes hyponatremia, -glycemia, or -calcemia occurs, and blood creatinine levels increase.

Overdose

There is no information regarding poisoning with Tygacil. When the drug was administered intravenously to volunteers in a dose of 0.3 g (1-hour infusion), an increase in vomiting with nausea was observed.

It is not possible to excrete tigecycline from the body using hemodialysis.

Interactions with other drugs

In case of combined use of the drug with warfarin (1-time dose of 25 mg), there is a decrease in the clearance of S- and R-warfarin (by 23% and 40%), and in addition, a decrease in the AUC of warfarin (by 29% and 68%). The mechanism of the described interaction has not yet been determined. Due to the ability of tigecycline to increase the level of PT/INR and APTT, in case of administration of the drug together with anticoagulants, the data of the corresponding coagulation tests should be constantly monitored.

Combining an antibiotic with oral contraception may reduce the effectiveness of the latter.

When administered via a T-shaped catheter, Tygacil is not compatible with diazepam, omeprazole, liposomal amphotericin B and amphotericin B alone, as well as with esomeprazole.

Storage conditions

Tygacil should be stored in a place out of reach of small children. Temperature values are a maximum of 25°C.

Shelf life

Tygacil can be used for an 18-month period from the date of manufacture of the therapeutic product.

Analogues

The analogs of the drug are Floracid, Furamag with Tigecycline and Dalacin.