Sigris

Sigris is an antithrombotic enzyme drug.

Indications of the sigris

It is used to eliminate sepsis with concomitant polyorganic insufficiency in acute form (with a high risk of fatal outcome).

[1],

Release form

Release in the form of lyophilizate for the manufacture of infusion solutions, in flasks of glass with a volume of 5 or 20 mg. The package contains 1 bottle of powder.

[2]

Pharmacodynamics

Drotrekogin-α (in active form) is an external element of the activated protein of type C (this component plays an important role in modulating the systemic reaction of the human body to the infectious process). Protein type C in the active form has an effect on antithrombotic properties, slowing down the factors Va, and also VIIIa. The information obtained as a result of in vitro tests demonstrates that the protein of group C has an indirect profibrinolytic effect, because it is able to slow down the element of IAP-1, and in addition to restrict the production of a thrombin-activated element that inhibits the fibrinolysis process.

Together with this, in vitro indications revealed that the protein of group C has anti-inflammatory properties that result from the suppression of tumor necrosis factors bound by monocytes, and in addition to blocking the leukocyte adhesion processes with respect to selectin, and limiting the thrombin-induced inflammatory response within vascular endothelium in the microcirculatory system.

A mechanism that allows active drotrekogin-α to reduce mortality in people with severe sepsis, until the end is not clear. In patients with severe sepsis, infusion of the drug, lasting 48 or 96 hours, caused a decrease in D-dimer values, depending on the size of the dosage, and in addition IL-6.

In comparison to people who received placebo, people who used drotrecoagin-α had a higher rate of decrease in IAP-1, D-dimer, and in addition, thrombin-antithrombin prothrombin F1.2, as well as IL- 6. Along with this, an accelerated increase in the values of antithrombin with a protein of type C was detected, and the stabilization of plasminogen parameters.

Given the duration of the infusion procedure, it was found that the peak drug effects of the active drug component relative to the D-dimer index were noted at the end of the 96th hour of the infusion (in the amount of 24 μg / kg / h).

[3]

Pharmacokinetics

Drotrekogin-α, together with the internal active protein of group C, is inactivated by internal inhibitors of the plasma protease. The level of protein C type inside the plasma of a healthy person, as well as a person with a severe degree of sepsis, is often below the minimum possible level for determining the concentration.

In people with severe sepsis, infusion of the drug at a rate of 12-30 μg / kg / h rather quickly forms equilibrium indices proportional to the infusion rate. The average values of clearance of the drug are equal to 40 liters / hour (within 27-52-x l / h). Average equilibrium values, which are 45 ng / ml (within 35-62-ng / ml), were observed after 2 hours after the start of the infusion procedure.

In many patients, the plasma level of Drotekogin-α decreased below the minimum mark, which allows to determine its amount, equal to 10 ng / ml, during 2 hours from the moment of completion of the infusion procedure. The level of drug clearance in people with severe sepsis is approximately 50% higher than that of a healthy person.

[4], [5],

Dosing and administration

The infusion is administered by the intravenous method, at a rate of 24 μg / kg / h. The entire infusion procedure should last for 96 hours.

The interrupted infusion should be resumed at the above standard rate. Increase the dosage size or use bolus injections is prohibited.

[7]

Use of the sigris during pregnancy

There is no information on the likelihood of adverse effects of the drug on the fetus if used by pregnant women, and in addition, on the impact of Sigris on reproductive activity. The use of the drug during pregnancy is allowed only in cases where the probability of beneficial effects on a woman exceeds the possibility of complications in the fetus.

There is no information on the possibility of drug intrusion into the mother's milk or systemic absorption after penetration of the substance into the gastrointestinal tract. But, because many drugs are excreted with breast milk, and besides this, because of the high risk of negative reactions in the baby, it is required to refuse breastfeeding during the period of drug use.

Contraindications

The main contraindications:

• presence of ongoing endogenous bleeding;
• The stroke of hemorrhagic type transferred in the period of 90 previous days;
• The surgery carried out in the period of 60 previous days inside the skull either in the region of the spinal cord or in the presence of an existing heavy head injury;
• trauma, in which there is a high probability of life-threatening bleeding;
• the presence of an epidural type catheter;
• a tumor inside the skull or symptoms of a hernia in the brain;
• diagnosed hypersensitivity to Droscrocogin-α.

There is no information on the efficacy and safety of drug use in infants in the gestational period (up to 38 weeks), as well as in children and adolescents under the age of 18.

Side effects of the sigris

The drug can cause side effects in the hemopoietic system: bleeding, which often appears during the infusion.

[6]

Overdose

There is information about the development of poisoning due to the introduction of an excessively high dosage of drugs. In many cases (with a dosage that is 60 times the standard infusion), no negative reactions were noted. In the rest, the victims developed hemorrhages due to sepsis.

There is no information on the existence of antidotes. If a patient develops an overdose, it is necessary to immediately stop the infusion of the drug and closely monitor the possible appearance of bleeding, while performing symptomatic therapy in parallel.

[8]

Interactions with other drugs

People with severe sepsis did not study the drug's interaction with other drugs. It is necessary to use with caution Sigris in combination with other drugs that affect the processes of hemostasis.

When combined with unfractionated heparin (in small doses: <15,000 U / day), and in addition to low-molecular heparin (for prevention - at 2850 units / day), there was no adverse effect on the properties of the drug and increased risk of bleeding in severe form this includes also bleeding in the central nervous system).

As a result of the use of heparin in small doses, the frequency of bleeding (non-life-threatening) increased in comparison with placebo values during the testing period (during the first 6 days). Small portions of heparin can be prescribed in combination with Sigris - as a means of preventing existing venous thrombosis. It is forbidden to interrupt prophylactic use of heparin until the moment when medical indications allow it to be done.

[9], [10]

Storage conditions

The lyophilizate must be contained in the refrigerator. It is necessary to avoid exposure to sunlight, and to limit access to medicines for young children. Temperature values are within 2-8 ° С.

Shelf life

Sigris is allowed to use in the period of 3 years from the date of manufacture of the drug. At the same time, the finished solution can be stored in the refrigerator for a maximum of 24 hours (this includes the time spent on its preparation).