Tigacil

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

Contains the element tigecycline, which exhibits a broad range of antibacterial effects. But 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 is not cross-resistant to most antibiotic subgroups. [2]

Indications Tigacil

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

Release form

The release of a drug substance is realized in the form of a powder for an infusion liquid, inside glass vials with a volume of 5 ml. There are 10 such bottles inside the pack.

Pharmacodynamics

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

Tigecycline is able to demonstrate 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 noted. [3]

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

Pharmacokinetics

Absorption.

Due to the fact that tigecycline is administered intravenously, it has 100% bioavailability.

Distribution processes.

In the case of using concentrations in the range of 0.1-1 μg / ml, the protein synthesis of tigecycline in vitro fluctuates approximately in the range of 71-89%. During pharmacokinetic tests with the participation of humans and animals, it was revealed that the substance is distributed at a high speed inside tissues.

Inside the body, the equilibrium level Vd of tigecycline is 500-700 liters, from which it can be inferred that the substance is distributed extensively, outside the plasma, and also accumulates inside the tissues.

There is no information on the ability of the drug to overcome 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 indicator for the range of 0-12 hours is 2349 ± 850 ng × hour / ml.

Exchange processes.

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

Tigecycline does not inhibit metabolic processes that develop with the help of 6 isoenzymes (CYP1A2 and CYP2C8, and in addition CYP2C9 with CYP2C19 and CYP2D6 together with CYP3A4). The substance does not show a competitive or irreversible inhibitory effect relative to the hemoprotein P450.

Excretion.

It was revealed that 59% of the administered portion is excreted by the intestines (while the main part of the unchanged element is excreted in the bile), and another 33% through the kidneys. Additional routes of excretion are glucuronidation processes and renal excretion of the unchanged component.

Dosing and administration

The medication is administered intravenously through a dropper in the period of 0.5-1 hour. The size of the initial dosage is 0.1 g; in the future, it is necessary to enter 0.05 g of the substance at 12-hour intervals.

The therapeutic cycle for complications of infections in the intra-abdominal zone or in the area of the subcutaneous layer with the epidermis lasts 5-14 days; in the case of ambulatory 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 persons under the age of 18).

Use Tigacil during pregnancy

Prescribing Tigacil to pregnant women is allowed only with strict indications, when the expected benefit for the woman is more likely than the risks of complications in the fetus.

There is no information on whether tigecycline is excreted in mother's milk. If the appointment of a medication is required for HB, it is necessary to refuse breastfeeding for the duration of therapy.

Contraindications

The main contraindications:

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

Caution is required when using in persons with severe liver failure.

Side effects Tigacil

Among the side effects:

• violations of the blood-clotting function: often there is an increase in the values of PTT / INR or APTT;
• problems with the work of the hematopoietic system: sometimes eosinophilia is observed. The development of thrombocytopenia is singly noted;
• manifestations of allergy: single anaphylactoid / anaphylactic symptoms are observed;
• disorders of the central nervous system: dizziness often occurs;
• lesions affecting the CVS: phlebitis often develops. Sometimes thrombophlebitis appears;
• digestive disorders: in most cases, vomiting, diarrhea and nausea appear. Abdominal pain, anorexia, and dyspepsia are common. Sometimes there is hyperbilirubinemia, pancreatitis in the active phase and jaundice, and ALT with AST increases. Liver failure and severe hepatic dysfunctions appear singly;
• dermatological lesions: rashes and itching are often observed;
• problems with sexual function: sometimes there is thrush, leucorrhea, or vaginitis;
• local signs: sometimes there is pain, phlebitis, inflammation or swelling in the injection area;
• others: often asthenia or headache occurs and wound healing is slowed down. Chills are sometimes observed;
• change in test readings: hypoproteinemia often develops or serum alkaline phosphatase, blood urea nitrogen and serum amylase values increase. Sometimes hyponatremia, β-glycemia, or β-calcium occur, and blood creatinine levels also increase.

Overdose

There is no information regarding Tigacil poisoning. With intravenous administration of the drug to volunteers in a portion of 0.3 g (1-hour infusion), there was an increase in vomiting with nausea.

It is impossible to excrete tigecycline from the body using hemodialysis.

Interactions with other drugs

In the case of the combined use of the drug with warfarin (1-time portion 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%)... It has not yet been possible to determine the mechanism of the described interaction. Due to the ability of tigecycline to increase the level of PTT / INR and APTT, in the case of administration of drugs together with anticoagulants, the data of the corresponding coagulation tests should be constantly monitored.

Combining an antibiotic with oral contraception can weaken the effectiveness of the latter.

In the case of administration through a T-shaped catheter, Tigacil is not compatible with diazepam, omeprazole, liposomal amphotericin B and just amphotericin B, as well as with esomeprazole.

Storage conditions

Tigacil should be kept out of the reach of small children. Temperature values - maximum 25 ° C.

Shelf life

Tigacil can be used for 18 months from the date of manufacture of the therapeutic product.

Analogs

The analogs of drugs are the substances Floracid, Furamag with Tigecycline and Dalatsin.