Baindrok^® (Solution) Instructions for Use

Marketing Authorization Holder

Aspectus Pharma LLC (Russia)

Manufactured By

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

V03AB35 (Sugammadex)

Active Substance

Sugammadex

Dosage Form

Baindrok®

Solution for intravenous administration 100 mg/ml

Dosage Form, Packaging, and Composition

Solution for intravenous administration

2 ml – vials (10 pcs.) – carton packs – By prescription

Pharmacotherapeutic Group

Other therapeutic products; antidotes

Pharmacological Action

Neuromuscular blockade reversal agent. Sugammadex is a modified gamma-cyclodextrin. It forms a complex with the peripheral muscle relaxants rocuronium and vecuronium, reducing the number of molecules binding to nicotinic acetylcholine receptors in the neuromuscular junction. This leads to the reversal of neuromuscular blockade induced by rocuronium or vecuronium.

A clear dose-dependent effect of sugammadex has been demonstrated.

Sugammadex can be used at different times after the administration of rocuronium or vecuronium bromide.

Pharmacokinetics

When administered intravenously as a bolus injection, Sugammadex exhibits linear kinetics in doses ranging from 1 to 16 mg/kg.

Following IV administration to adult patients, Sugammadex has the following pharmacokinetic parameters: a rapid distribution phase with a distribution half-life of 2.9 minutes; a slow distribution phase with a distribution half-life of 27 minutes; a T_1/2 of 2.2 hours and a V_d at steady state of 15 liters, plasma clearance of 91 ml/min.

It does not bind to plasma proteins or erythrocytes. Sugammadex metabolites have not been detected. More than >90% of the dose is excreted within 24 hours. 96% of the dose is excreted in the urine, of which 95% is unchanged Sugammadex. Excretion in feces and exhaled air is <0.02%.

In patients with impaired renal function, the clearance of sugammadex is decreased, and T_1/2 is increased.

In patients aged 75 years, sugammadex clearance shows a tendency to decrease, and T_1/2 shows a tendency to increase, compared to patients aged 40 years.

In children aged 8 and 15 years, the T_1/2 of sugammadex is 0.9 hours and 1.7 hours, respectively, the V_d at steady state is 3.1 liters and 9.1 liters, and clearance is 41 ml/min and 71 ml/min.

Indications

For reversal of neuromuscular blockade induced by rocuronium or vecuronium in adults.

ICD codes

Dosage Regimen

Administer intravenously as a bolus injection, as a single dose, rapidly (over 10 seconds), directly into a vein or into an existing intravenous line.

The dose of sugammadex depends on the degree of neuromuscular blockade that needs to be reversed and does not depend on the anesthesia regimen.

Sugammadex can be used for reversal of neuromuscular blockade of varying depth induced by rocuronium or vecuronium.

Adverse Reactions

Nervous system disorders Common – complications during anesthesia indicating recovery of neuromuscular function (including limb or body movements, coughing during the anesthesia procedure or during the surgery itself, grimacing or sucking on the endotracheal tube); in isolated cases – unintended return of consciousness during anesthesia (a causal relationship with sugammadex use has not been reliably established); when administered at doses lower than optimal (<2 mg/kg) in 2% of cases – recurrence of blockade.

Special senses disorders Very common – dysgeusia (metallic or bitter taste in the mouth), occurring when sugammadex is used at a dose of 32 mg/kg and higher in healthy volunteers.

Respiratory system disorders In patients with a history of pulmonary complications, bronchospasm may occur (a causal relationship with sugammadex use has not been reliably established). The physician should be warned about the possible development of bronchospasm.

Allergic reactions Possible – redness, mild erythematous rash.

Contraindications

Severe renal failure (CrCl <30 ml/min), severe hepatic failure, pregnancy, lactation (breastfeeding), children under 2 years of age, hypersensitivity to sugammadex.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic failure.

Use in Renal Impairment

Contraindicated in severe renal failure (CrCl < 30 ml/min).

Pediatric Use

Contraindicated in children under 2 years of age.

Special Precautions

Sugammadex is to be used only by an anesthesiologist or under their supervision. The use of appropriate neuromuscular monitoring techniques is recommended to monitor recovery from neuromuscular blockade.

It is recommended to monitor the patient’s condition in the postoperative period to prevent cases of recurrence of blockade.

Until adequate spontaneous breathing is restored after reversal of neuromuscular blockade, mechanical ventilation is mandatory.

Lung ventilation may be prolonged when drugs that depress respiratory function are used.

If neuromuscular blockade recurs after extubation, adequate lung ventilation must be ensured.

Clinical studies have reported recurrence of blockade when sugammadex was used at doses lower than optimal. To prevent recurrence of blockade, Sugammadex should be used at the doses recommended for standard or immediate reversal.

If re-administration of rocuronium or vecuronium is necessary, the recommended waiting time is 24 hours. If neuromuscular blockade is required before the recommended waiting time has elapsed, a non-steroidal neuromuscular blocking agent should be used.

When reversing neuromuscular blockade during anesthesia, a reduction in the depth of anesthesia (e.g., movements, coughing, grimacing, tracheal tube sucking) has sometimes been observed; therefore, when reversing anesthesia, additional doses of anesthetics or opioids should be administered.

Due to the use of certain drugs after sugammadex, a displacement-type interaction is possible – displacement of rocuronium and vecuronium by sugammadex. As a result, recurrence of blockade may occur. In such cases, mechanical ventilation must be applied. If the drug that caused the displacement is administered by infusion, the infusion should be stopped. In cases where a potential interaction of this type can be expected, the patient’s condition should be carefully monitored for symptoms of recurrence of blockade (for about 15 minutes) after parenteral administration of a drug that occurred within 6 hours of sugammadex administration. Displacement-type interaction has been noted for some medicinal products (toremifene, flucloxacillin, and fusidic acid).

When using drugs that enhance neuromuscular blockade in the postoperative period, the possibility of recurrence of blockade must be taken into account. Refer to the prescribing information for rocuronium or vecuronium for specific information regarding drugs that enhance neuromuscular blockade. In case of recurrence of blockade, the patient may require mechanical ventilation or re-administration of sugammadex.

There are no data on the use of sugammadex in intensive care settings.

Sugammadex should not be used to reverse neuromuscular blockade caused by other muscle relaxants, as data on efficacy and safety are lacking.

The safety and efficacy of sugammadex for reversal of neuromuscular blockade caused by other muscle relaxants has not been studied, therefore it should not be used in such cases.

When using sugammadex, the effectiveness of some drugs may decrease due to a reduction in their plasma concentrations. In such cases, the possibility of re-administering the drugs, administering therapeutically equivalent drugs (preferably from a different chemical class) and/or non-pharmacological intervention should be considered.

In vitro studies have noted a pharmacodynamic interaction (prolongation of aPTT and prothrombin time) with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban, and dabigatran.

Given the short-term effect of sugammadex on prolonging aPTT or prothrombin time, it is unlikely that sugammadex, when used as monotherapy or in combination with other drugs, increases the risk of bleeding. Since information on the use of sugammadex in patients with established coagulopathy is insufficient, coagulation parameters should be carefully monitored in accordance with standard clinical practice.

In patients with severe renal impairment (CrCl <30 ml/min), the elimination of sugammadex and the Sugammadex-rocuronium complex is slowed, but no symptoms of recurrence of neuromuscular blockade have been identified. Data from a limited number of patients with renal failure on dialysis indicate an inconsistent decrease in plasma sugammadex concentration during hemodialysis. The use of sugammadex in patients with severe renal failure is not recommended.

No dose adjustment is necessary in mild to moderate hepatic impairment, since Sugammadex is primarily excreted by the kidneys. Use with caution in patients with severe hepatic impairment.

In conditions accompanied by slowed blood flow (e.g., cardiovascular disease, old age, edema), the recovery time may be prolonged.

The risk of developing allergic reactions and the need to take measures to prevent them should be considered.

In general, Sugammadex does not affect laboratory parameters, with the probable exception of the quantitative determination of progesterone in blood serum. Interference with this test is possible at a plasma sugammadex concentration of 100 µg/ml.

Use in pediatrics

In pediatrics, Sugammadex is recommended only for standard reversal of rocuronium-induced blockade.

Data on the efficacy and safety of sugammadex in children are limited. For standard reversal of rocuronium-induced neuromuscular blockade upon reappearance of T₂, the recommended dose of sugammadex for children aged 2-17 years is 2 mg/kg. Other standard reversal situations and immediate reversal have not been studied, therefore the use of the drug is not recommended until further information is available.

In case of use in children, Sugammadex can be diluted with 0.9% sodium chloride solution to a concentration of 10 mg/ml.
The use of sugammadex in neonates and children under 2 years of age is not recommended as experience in this age group is extremely limited.

Drug Interactions

Drug interactions of sugammadex with toremifene, flucloxacillin, and fusidic acid cannot be excluded (clinically significant displacement-type interaction is not anticipated), with hormonal contraceptives (clinically significant displacement-type interaction is not anticipated).

For toremifene, which has a relatively high affinity constant and relatively high plasma concentration, there is a possibility of displacement of vecuronium or rocuronium from the complex with sugammadex. Therefore, recovery of the T₄/T₁ ratio to 0.9 may be delayed in patients who received toremifene on the day of surgery.

IV administration of high doses of flucloxacillin (infusion of 500 mg or more) or fusidic acid may lead to displacement of rocuronium or vecuronium from the complex with sugammadex. The use of high doses of flucloxacillin or fusidic acid in the preoperative period may lead to a delay in the recovery of the T₄/T₁ ratio to 0.9. The use of these drugs in high doses in the postoperative period (up to 6 hours) should be avoided. If the use of flucloxacillin or fusidic acid is unavoidable, lung ventilation should be strictly controlled, especially during the subsequent 15 minutes.

Interaction between sugammadex at a dose of 4 mg/kg and progesterone may lead to a reduction in the effect of progesterone (34% AUC), which is similar to the reduction observed when a daily dose of an oral contraceptive is taken 12 hours later; this, in turn, may lead to reduced efficacy. For estrogens, a reduction in effect can be expected. Therefore, administration of a bolus dose of sugammadex is considered equivalent to one missed daily dose of oral contraceptives. If an oral contraceptive was taken on the day of sugammadex administration, one should act as if a dose was missed, in accordance with the instructions for use of the oral contraceptive.

In case of using oral contraceptives, the patient should use an additional non-hormonal contraceptive method for the next 7 days.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.