Cellex^® (Solution) Instructions for Use

Marketing Authorization Holder

Pharma-Sintez, JSC (Russia)

Manufactured By

Deko Company, LLC (Russia)

Labeled By

Deko Company, LLC (Russia)

Or

Farm-Sintez, LLC (Russia)

Quality Control Release

Pharma-Sintez, JSC (Russia)

Contact Information

Pharma-Sintez JSC (Russia)

ATC Codes

N06BX (Other psychostimulants and nootropic agents)

N07XX (Other nervous system drugs)

Active Substance

Polypeptides of the pig embryos brain (Grouping name)

Dosage Form

Cellex®

Subcutaneous injection solution 0.1 mg/1 ml: amp. 1 ml or 2 ml 1, 2, 4, 5 or 10 pcs. in a kit with a sterile syringe filter

Dosage Form, Packaging, and Composition

Solution for s.c. administration transparent, colorless or light yellow, odorless or with a specific odor; opalescence is allowed; the presence of individual coagulum strands is allowed.

Excipients: glycine – 3.75 mg, sodium chloride – 5.85 mg, sodium hydrogen phosphate dodecahydrate – 1.8 mg, water for injection – up to 1 ml.

* Composition per 1 ml.
Active substance Polypeptides of the pig embryos brain, in terms of total protein – 0.9-2.4 mg (nominal total protein content 1.65 mg per 1 ml of substance).
Excipients glycine – 3.75 mg, 0.1M disodium hydrogen phosphate solution – to pH 7.8 (about 0.8 mg of dry substance), sodium chloride – 5.85 mg, polysorbate 80 – 0.005 mg, purified water – up to 1 ml.

1 ml – dark glass ampoules (1) – contour cell packs (1) – cardboard packs.
1 ml – dark glass ampoules (1) – contour cell packs (2) – cardboard packs.
1 ml – dark glass ampoules (2) – contour cell packs (1) – cardboard packs.
1 ml – dark glass ampoules (2) – contour cell packs (2) – cardboard packs.
1 ml – dark glass ampoules (5) – contour cell packs (1) – cardboard packs.
1 ml – dark glass ampoules (5) – contour cell packs (2) – cardboard packs.
2 ml – dark glass ampoules (1) – contour cell packs (1) – cardboard packs.
2 ml – dark glass ampoules (1) – contour cell packs (2) – cardboard packs.
2 ml – dark glass ampoules (2) – contour cell packs (1) – cardboard packs.
2 ml – dark glass ampoules (2) – contour cell packs (2) – cardboard packs.
2 ml – dark glass ampoules (5) – contour cell packs (1) – cardboard packs.
2 ml – dark glass ampoules (5) – contour cell packs (2) – cardboard packs.

The pack includes sterile syringe filters Millex-GV^®, from Merck Millipore with a pore size of 0.22 µm or ABLUO^® from GVS Filter Technology with a pore size of 0.2 µm, or Sterifix^® Pury from B. Braun Melsungen AG with a pore size of 5 µm in a quantity equal to the number of ampoules.

Clinical-Pharmacological Group

Nootropic drug

Pharmacotherapeutic Group

Nootropic drugs, other agents affecting the nervous system

Pharmacological Action

The polymodal action of the drug Cellex^® is due to the presence of native tissue-specific proteins and polypeptides of stem and progenitor cells from pig embryos brain.

The main part of the protein molecules of the drug Cellex^® are proenzymes belonging to the class of protein kinases and regulators of cellular metabolism, which are activated during changes in tissue homeostasis with individual tissue-specific regulation. Protein-polypeptide factors of growth and differentiation of nerve cells, regulators of apoptosis and autophagy processes, as well as signaling proteins – mitogens and morphogens of embryogenesis provide the neuroprotective and neuroreparative action of the drug.

The direct neuroprotective action of the drug is carried out by regulating the concentrations of the neurotransmitter pool, which leads to inhibition of the spillover of excitatory amino acids (aspartate and glutamate) and an increase in the level of inhibitory neurotransmission (gamma-aminobutyric acid and taurine). Stimulation of GABAergic neurotransmission inhibits cationic destabilization of the membranes of the neuronal and glial cell pool, and activates alternative pathways for the synthesis of macroergic molecules – GTP by triggering the aminobutyrate shunt of the Roberts cycle.

Activation of secondary neuroprotection occurs due to the restoration of autophagy signals, stimulation of synaptogenesis, dendritogenesis and axonogenesis processes, improvement of tissue immunoregulation with inhibition of immunogenic cytotoxicity of macrophages. Reduced expression of glial fibrillary acidic protein (GFAP) by astrocytes in the focus of brain tissue necrosis and the penumbra zone reduces the level of astrogliosis, regulating the processes of remyelination and restoration of the blood-brain barrier. At the same time, a tissue-specific and systemic action of the drug is noted with the restoration of the regenerative-reparative potential of brain cells, a decrease in the number of damaged cells and the severity of perifocal edema in the penumbra zone (allows to achieve a significant limitation of the focus of brain tissue necrosis) with the restoration of microcirculation and general perfusion of the nervous tissue.

The systemic effect of growth factors, differentiation and signaling molecules ensures a reduction in the rehabilitation time of patients with damage to the central and peripheral nervous system of vascular genesis and contributes to the restoration of motor, sensory and cognitive functions.

Clinical efficacy and safety

Acute cerebrovascular accident (ischemic and hemorrhagic type)

Data from conducted clinical studies CEL-09, TSEL-IV-2013 and numerous observational studies have proven the high efficacy of the drug Cellex^® in restoring focal neurological deficit, higher cortical functions, speech and mnestic disorders in acute cerebrovascular accident of ischemic and hemorrhagic type.

The absence of the need to verify the type of stroke (ischemic or hemorrhagic) allows starting the use of the drug at the first clinical signs of cerebrovascular accident.

Chronic cerebral ischemia with mild and moderate neurocognitive disorders of vascular genesis

The CogniCell/2018 clinical study showed the achievement of the primary endpoint of the study with improvement of cognitive functions in 47.7% of patients who reached the normal state of this indicator on the MoCA scale (>26 points). Analysis of secondary endpoints showed significant differences with improvement of cognitive functions in the group of patients receiving the drug Cellex^® on the MoCA scale, Frontal Assessment Battery and a decrease in the level of anxiety and depression on the HADS scale.

The dynamics of blood plasma biomarkers in patients with chronic cerebral ischemia against the background of therapy with the drug Cellex^® showed an increase in the expression of the glial growth factor GDNF throughout the study, with a decrease in the concentration of GFAP by the end of the first course of therapy.

Pharmacokinetics

The complex composition of the drug Cellex^®, the main biologically active components of which are native tissue-specific proteins and polypeptides of embryonic nervous tissue, which have a total polyfunctional action, similar in composition, structure and functions to the patient’s proteins, does not allow for the usual pharmacokinetic analysis of individual components.

Indications

In adult patients for the treatment of cerebrovascular diseases

• Acute cerebrovascular accidents in the acute and early rehabilitation period of the disease as part of complex therapy;
• Chronic cerebral ischemia with mild and moderate neurocognitive disorders of vascular genesis.

ICD codes

Dosage Regimen

Adults

For acute cerebrovascular accidents, the drug is prescribed at a dose of 0.1-0.2 mg once a day s.c. for 10 days, depending on the severity of the patient’s condition. If necessary, a repeated course is carried out after 10 days.

Patients with chronic cerebral ischemia and mild or moderate neurocognitive disorders of vascular genesis are prescribed the drug at a dose of 0.1 mg/ml once a day s.c. for 10 days. If necessary, a repeated course is carried out after 10 days.

Rules for solution administration

The drug is administered subcutaneously through a sterile syringe filter included in the kit.

After drawing the drug from the ampoule through the injection needle, air bubbles are expelled from the syringe. The used needle is removed. A sterile filter is attached to the syringe. A new needle is attached to the filter cannula. Subcutaneous administration of the drug is performed.

It is unacceptable to expel air bubbles from the syringe through the attached filter. An attempt to release air through a wet filter membrane may lead to its obstruction for the drug.

Adverse Reactions

Immune system disorders allergic reactions in the form of mild hyperemia at the injection site, hypersensitivity reactions (skin rash, itching, angioedema).

Nervous system disorders sleep disturbance, headache.

General disorders subfebrile temperature.

Contraindications

• Hypersensitivity to the components of the drug;
• Epilepsy;
• Manic psychosis;
• Productive delusions;
• Delirium;
• Age under 18 years (due to insufficient clinical data).

With caution in case of a history of allergic reactions to drugs of protein-peptide nature.

Use in Pregnancy and Lactation

Due to the lack of relevant studies, the use of the drug during pregnancy and breastfeeding is contraindicated.

Pediatric Use

The use of the drug in children and adolescents under 18 years of age is contraindicated.

Special Precautions

The drug Cellex^® should be used with caution in combination with hypoglycemic agents (risk of hypoglycemia during insulin therapy and during the use of oral hypoglycemic agents).

It is prescribed with particular caution in malignant arterial hypertension in the stage of decompensation; sympathoadrenal crises of the panic attack type; severe anxiety-depressive disorders.

Several days before general anesthesia with chloroform or ether, it is necessary to stop taking the drug (increased risk of psychomotor agitation, delirium).

During treatment with the drug Cellex^®, it is not recommended to consume alcohol (reactions of agitation and psychomotor agitation are possible).

The drug should be discontinued before testing the content of catecholamines, normetanephrine and vanillylmandelic acid in blood and urine; titers of antinuclear antibodies.

The drug does not contain prion infections and viruses.

Children

Studies of the efficacy and safety of the drug in children under 18 years of age have not been conducted.

Effect on the ability to drive vehicles and mechanisms

Currently, there are no data on the effect of the drug Cellex^® on the ability to drive vehicles and mechanisms requiring increased attention and speed of mental and motor reactions.

Overdose

Currently, no cases of overdose of the drug Cellex^® have been reported.

Drug Interactions

When used concomitantly with psychostimulant drugs and alcohol, psychomotor agitation and sleep disturbances are possible.

A decrease in the activity of anesthetic agents, tranquilizers, and neuroleptics is possible.

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, at a temperature not exceeding 8°C (46.4°F).

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

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.