Rastan

Rastan is a lyophilisate for the preparation of injection solutions. In addition, it is accompanied by a 0.3% solution of metacresol, which is a solvent. The drug contains the substance somatropin and is classified as a somatropin agonist.

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Indications Rastana

It is used to treat children with growth disorders caused by insufficient secretion of somatotropin, as well as gonadal dysgenesis (Ulrich syndrome). In addition, it is used to treat chronic childhood renal failure (against the background of growth retardation).

Adults are prescribed it as a replacement therapy for somatotropin deficiency.

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Release form

The product is released in vials of 1.3 (4 IU) or 2.6 mg (8 IU). Additionally, a solvent is included in a 1 ml container.

It can also be produced in a container with a volume of 5.3 (16 IU) or 8 mg (24 IU), which comes with a special solvent inside a 2 ml bottle.

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Pharmacodynamics

The substance somatropin is a single-chain polypeptide that includes 191 amino acid residues (human somatotropin), produced by the genetically modified strain of Escherichia coli BL21 (DE3)/pES1-6.

Somatropin is a metabolic type hormone that affects protein, lipid, and carbohydrate metabolism. In growing children, in the case of a deficiency of internal STH, this substance accelerates the process of linear skeletal growth.

Just like in adults, this hormone helps maintain the required body structure in children, improving nitrogen absorption, and also releasing lipids from fat depots and increasing the growth rate of skeletal muscles. Internal fat tissues are particularly sensitive to somatropin.

In addition to stimulating lipolysis activity, the active substance reduces the amount of triglycerides entering fat depots. Along with this, somatropin increases serum levels of IGF-I elements, and along with this, IGF-3B-3.

In addition to the above effects, somatropin has the following properties:

• lipid metabolism: stimulation of liver conductors in relation to LDL, as well as an effect on the lipid and lipoprotein profile in the serum. The use of somatropin in people with a deficiency of STH causes a decrease in the indicators of apolipoprotein type B, as well as LDL in the serum. In addition, a decrease in the values of total cholesterol is possible;
• carbohydrate metabolism: increased insulin levels; fasting glucose levels usually do not change. Children with Sheehan syndrome may develop fasting hypoglycemia, and somatropin can correct this condition;
• water-salt metabolism: deficiency of somatropin is associated with a decrease in tissue fluid volumes, as well as plasma indices. Each of these values quickly begins to increase after the use of somatropin. This substance also prevents the increase in potassium and sodium with phosphorus;
• bone metabolism: the drug promotes activation of bone metabolism. In people with observed deficiency of somatropin hormone, as well as osteoporosis, long-term use of somatropin helps restore bone density, and along with this, mineral composition;
• physical performance: the use of the drug helps to increase physical endurance, as well as muscle strength. The active substance can increase cardiac output, but it has not yet been possible to determine how this occurs. It is possible that this may be associated to a certain extent with a decrease in peripheral vascular resistance.

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Pharmacokinetics

After the injection of the drug by the subcutaneous method, the level of bioavailability of the substance reaches 80%. The drug reaches its peak values after 4-6 hours. The half-life is 3 hours.

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Dosing and administration

The injection of the medicine should be administered slowly, subcutaneously. It is better to carry out the procedure in the evening. The medicine is diluted in 1 ml of solvent (release form 1.3 (4 IU) or 2.6 mg (8 IU)) or in 2 ml of solvent (release form 5.3 (16 IU) or 8 mg (24 IU)). The procedure is performed by taking the solvent with a syringe - with its subsequent introduction into the container with the medicine through the stopper. It is necessary to wait until the drug is completely dissolved. It is prohibited to shake the bottle sharply.

The dosage is selected individually, taking into account the patient’s weight or body surface area, the degree of hormone deficiency, and the effectiveness of the medication used.

To eliminate the deficiency of somatotropin in adults, the initial dosage should be administered once a day (0.006 mg/kg (or 0.018 IU/kg)), and then, taking into account the effect of the drug, it should be increased to 0.012 mg/kg (or 0.036 IU/kg), also once a day. For the elderly, the dosage should be reduced.

In case of growth disorders due to insufficient secretion of somatotropin in children, 0.025-0.035 mg/kg (or 0.07-0.1 IU/kg) or 0.7-1 mg/m (or 2-3 IU/m²) should be administered once a day. If the desired effect is achieved, the therapy may be terminated.

Treatment should be started as soon as possible after diagnosis and continued until:

• the growth rate during therapy will not decrease to 2 cm/year or less;
• closure of the epiphyseal growth areas will not occur;
• the socially acceptable height indicator will not be reached (for girls it is about 155-160 cm, and for boys – about 165-170 cm);
• bone age will not be reached (for girls - approximately 14-15 years, and for boys - approximately 16-17 years).

If STH deficiency develops during childhood and persists into adolescence, therapy must be continued until full somatic development (bone mass and body structure) occurs.

Growth problems in Ullrich syndrome. Chronic renal failure in children that causes growth retardation.

The drug should be administered at a dose of 0.05 mg/kg (or 0.14 IU/kg) or 1.4 mg/m (or 4.3 IU/m²) once per day. If the growth dynamics are insufficient, a dose adjustment may be necessary.

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Use Rastana during pregnancy

It is prohibited to use the medicine during pregnancy or lactation (in this case, if it is necessary to use the drug, it is necessary to stop breastfeeding for the period of therapy).

Contraindications

Main contraindications:

• It is prohibited to prescribe the drug in case of symptoms of tumor growth. Antitumor treatment must be completed before starting to use Rastan injections;
• should not be used as a growth stimulant in children with closed epiphyseal growth areas of tubular bones;
• contraindicated for use by people suffering from an active form of diabetic retinopathy (preproliferative or proliferative type);
• it is necessary to discontinue the use of somatropin during the period of kidney transplantation in children with chronic renal failure;
• Somatropin should not be used in people who are in a critically life-threatening condition that has developed in an acute form following abdominal or open-heart surgery; or as a result of multiple injuries and acute respiratory failure;
• Use is prohibited if the patient has an intolerance to the active substance or other components of the drug.

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Side effects Rastana

Using the solution may cause the development of the following side effects:

• NS reactions: development of headaches, intracranial neoplasms (eg, arachnoid endothelioma) in young people/adolescents who in childhood underwent a therapeutic course to eliminate malignant tumors in the head using radiation in combination with somatropin, as well as an increase in intracranial pressure, carpal tunnel syndrome and hypoesthesia with paresthesia;
• connective tissues and muscle and bone structure: destruction of the heads of tubular bones, edematous syndrome, progressive scoliosis or dislocation in the area of the femoral head in children, as well as joint and muscle rigidity. There may also be pain in the limbs or their stiffness, myalgia with arthralgia, attacks of cramps and pain in the back; Perthes disease or aseptic necrosis in the area of the femoral head often develops in people of short stature;
• vascular system reaction: progressive form of diabetic retinopathy;
• reactions of the endocrine system: glucose intolerance disorder (including fasting hyperglycemia), and with it an overt degree of diabetes mellitus. Hypothyroidism (regular and latent central types), type 2 diabetes mellitus, gynecomastia and thyrotoxicosis, as well as premature thelarche may develop isolated cases;
• hematopoietic system and lymph: development of leukemia (the incidence of this pathology is similar for children with and without somatropin deficiency); a decrease in serum cortisol levels may be observed (possibly due to the effect of somatropin on transport proteins);
• immune reactions: skin rashes, general manifestations of hypersensitivity, as well as the production of antibodies against somatropin;
• kidneys and urinary system: the appearance of infections in the urinary tract, as well as the development of hematuria;
• gastrointestinal reactions: pancreatitis, as well as vomiting or nausea;
• reactions of the visual organs: visual impairment;
• manifestations at the injection site and systemic disorders: for adults, the most typical disorders are due to fluid imbalance (including a feeling of weakness, peripheral edema and pastosity of the legs). Such disorders are usually moderate or mild, occur during the initial months of therapy and resolve on their own or after a reduction in the dosage of the drug. The frequency of such reactions depends on the age of the patient, the size of the drug dose, and is also likely to be inversely proportional to the age at which the somatotropin deficiency occurred. In children, such complications rarely develop;
• children with Ullrich syndrome: development of respiratory pathologies (otitis, flu, tonsillitis with sinusitis and nasopharyngitis) or infections in the urinary tract;
• adults with a deficiency of STH: the appearance of headaches, weakness, pain in the back or limbs (also a feeling of stiffness), as well as hypoesthesia;
• manifestation in the injection area (this includes changes in the volume of adipose tissue): burning or pain after the procedure, rashes and itching, the appearance of bleeding, nodules, pigmentation and inflammation with fibrosis.

Myositis develops occasionally (it may be due to the effect of the preservative metacresol, which is a component of Rastan). The occurrence of severe pain or myalgia in the injection area may be a consequence of myositis. In the case of such a disorder, Rastan should be replaced with another drug containing somatropin, but which does not contain metacresol. Further therapy is carried out taking into account the benefit-risk ratio.

Problems such as sleep apnea, insomnia, worsening of existing psoriasis symptoms, increased blood pressure, and increased occurrence of moles may also occur.

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Overdose

In acute overdose, hypoglycemia may develop, which then develops into hyperglycemia. Prolonged overdose may cause acromegaly or gigantism.

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Interactions with other drugs

GCS can inhibit the medicinal effect of somatropin. If HRT is necessary, dosages and compliance must be carefully monitored to prevent the risk of adrenal insufficiency or inhibition of the growth-stimulating effect.

Somatropin is a stimulator of the activity of hemoprotein P450 (CYP). Because of this, it can reduce plasma levels (and, accordingly, reduce the effectiveness) of drugs that are metabolized by hemoprotein CYP3A. Such drugs include corticosteroids, sex hormones, anticonvulsants, and cycloserine.

Since STH can cause insulin resistance, it is necessary to monitor the patient for symptoms of diabetes or decreased glucose tolerance. Also, during therapy with somatotropin, it is necessary to closely monitor the condition of people who already have diabetes or decreased glucose tolerance.

Combined use with GCS can reduce the effect of somatropin. People with ACTH deficiency need to undergo HRT, carefully selecting the dosage of GCS - to avoid a suppressive effect on STH.

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Storage conditions

Rastan should be kept in a place protected from sunlight and inaccessible to children. It is prohibited to freeze the medicine. Temperature indicators are within 2-8°C.

Shelf life

Rastan is suitable for use within 2 years from the date of manufacture of the medicine. The ready solution can be stored for a maximum of 15 days.

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