Rastan

Rastan is a lyophilizate for the manufacture of injection solutions. In addition to it, a 0.3% solution of metacresol is applied, which is a solvent. The drug contains somatropin and is included in the category of somatropin agonists.

[1], [2]

Indications of the rastan

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 kidney failure of the kidney in a chronic form (against a background of growth retardation).

Adults are prescribed as a means of substitution treatment for a deficiency of somatotropin.

[3], [4], [5], [6], [7]

Release form

The release is carried out in vials with a volume of 1.3 (4 IU) or 2.6 mg (8 IU). In addition, a solvent is applied inside the container with a volume of 1 ml.

Also can be produced in a capacity of 5.3 (16 IU) or 8 mg (24 IU), to which a special solvent inside the 2 ml bottle is attached.

[8], [9]

Pharmacodynamics

Somatropin is a single-chain polypeptide that includes 191 amino acid residues (human somatotropin) produced by the genetically modified E. Coli strain BL21 (DE3) / pES1-6.

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

Just like adults, this hormone helps maintain the required body structure in the child, improving the assimilation of nitrogen, and in addition, releasing lipid from fat stores and increasing the rate of growth of skeletal muscles. Special sensitivity to somatropin is possessed by internal fat tissues.

In addition to stimulating lipolysis activity, the active substance reduces the amount of triglycerides entering the fat stores. Together with this, somatropin increases the serum indices of IGF-I elements, and at the same time, IFRPB-3.

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

• lipid metabolism: stimulation of hepatic conductors with respect to CLLP, as well as effects on the lipid and lipoprotein profile within the serum. The use of somatropin in people with a deficiency of STH causes a decrease in the indices of apolipoprotein type B, as well as LDL within the serum. In addition, it is possible to lower the values of total cholesterol;
• carbohydrate metabolism: increased insulin levels; fasting glucose values do not usually change. Children with Shiene's syndrome may develop fasting hypoglycaemia, and somatropin is able to correct this condition;
• water-salt metabolism: a deficiency of somatropic hormone is associated with a decrease in fluid volumes in tissues, as well as plasma indices. Each of these values quickly begins to increase after using somatropin. This substance also prevents the increase of potassium and sodium with phosphorus;
• bone metabolism: the drug promotes bone turnover. In people with an observed lack of somatropic hormone, and also with osteoporosis, somatropin used for a long time helps to restore bone density, and with it the mineral composition;
• physical working capacity: the use of the drug helps to increase physical endurance, as well as muscle strength. The active substance can increase cardiac output, but, by what way it happens, it has not been possible to find out yet. It is possible that this to a certain extent may be associated with a decrease in peripheral vascular resistance.

[10], [11]

Pharmacokinetics

After injection of the drug with SC, the level of bioavailability of the substance reaches 80%. Peak indicators of the drug reaches 4-6 hours later. Half-life is 3 hours.

[12], [13]

Dosing and administration

To inject an injection of a medicine it is necessary slowly, a method p / to. To conduct the procedure better in the evening. The drug is diluted in 1 ml of solvent (form of release 1.3 (4 IU) or 2.6 mg (8 IU)) or in 2 ml of solvent (form of release 5.3 (16 IU) or 8 mg (24 IU) )). The procedure is performed by removing the solvent with a syringe - and then introducing it into the container with the medicine through the plug. It is required to wait for complete dissolution of the drug. Do not shake the bottle sharply.

The dosage is selected individually - the weight or the surface area of the patient, the degree of hormone deficiency, and the effectiveness of the medicine used are taken into account.

To eliminate the lack of somatotropin, adults need to administer the initial dosage once a day (0.006 mg / kg (or 0.018 IU / kg)), and then, taking into account the effect of drugs, increase it to 0.012 mg / kg (or 0.036 IU / kg), also once per day. For the elderly, doses should be reduced.

In case of growth disorders due to inadequate release of somatotropin, children should be administered 0.025-0.035 mg / kg (or 0.07-0.1 IU / kg) or 0.7-1 mg / m (or 2-3 IU / m²) once per day day. When you get the desired effect, you can finish the therapy.

It is necessary to begin the course of treatment as soon as possible after the diagnosis and conduct it until:

• the growth rate during therapy will not decrease to a level of 2 cm / year or less;
• there will be no closure of epiphyseal growth areas;
• a socially acceptable growth rate (for girls it is about 155-160 cm, and for boys - about 165-170 cm) will not be achieved;
• will not reach the bone age (for girls - about 14-15 years, and for boys - about 16-17 years).

With the development of STH deficiency during childhood and its preservation during the adolescent period, it is necessary to continue therapy until there is a complete somatic development (bone mass and body structure).

Problems with growth in the syndrome Ulrich. Pediatric renal failure is a chronic type, in which there is a growth retardation.

It is required to administer the drug in the amount of 0.05 mg / kg (or 0.14 IU / kg) or 1.4 mg / m (or 4.3 IU / m²) once a day. If the growth dynamics of growth are insufficient, correction of the dose size may be necessary.

[22], [23], [24], [25], [26]

Use of the rastan during pregnancy

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

Contraindications

The main contraindications:

• It is forbidden to prescribe drugs in case of signs of growth of tumors. The antitumor treatment should be completed before the use of Rastan injections;
• It can not be used as a growth stimulant in children with closed epiphyseal growth sites of tubular bones;
• it is contraindicated for people suffering from an active form of diabetic retinopathy (pre-proliferative or proliferative type);
• it is necessary to abolish the use of somatropin for the kidney transplant period in children with chronic kidney failure;
• It is not possible to use somatropin in people who are in a critically life-threatening condition that developed in acute form after surgery on the peritoneum or open heart; or due to multiple injuries and respiratory failure in acute form;
• It is prohibited to use if the patient has intolerance of the active substance or other constituent elements of the medicine.

[14], [15], [16], [17], [18]

Side effects of the rastan

Use of the solution may cause the following side effects:

• HC reactions: development of headaches, neoplasms inside the skull (for example, arachnoidendothelioma) in young people / adolescents who have undergone a therapeutic course of eliminating malignant tumors in the head by irradiation in combination with somatropin, and in addition an increase in intracranial pressure, carpal tunnel syndrome canal and hypesthesia with paresthesia;
• connective tissues and the structure of muscles and bones: the destruction of the heads of bones tubular type, edematous syndrome, progressive scoliosis or dislocation in the head of the hip bone in children, but also joint and muscle rigidity. There may also be pain in the limbs or their stiffness, myalgia with arthralgia, seizures and pain in the back; Perthes disease or aseptic necrosis in the head of the hip bone often develops in people of low stature;
• vascular system reaction: progressive form of diabetic retinopathy;
• reactions of the endocrine system: a disorder of tolerance for glucose (among such disorders - fasting hyperglycemia), and with it an obvious degree of diabetes mellitus. Hypothyroidism (common as well as latent central species), type 2 diabetes mellitus, gynecomastia and thyrotoxicosis, as well as premature bodily can develop only occasionally;
• system of hematopoiesis and lymph: development of leukemia (the frequency of appearance of this pathology is similar for children with a deficiency of somatropic hormone, and also without it); there may be a decrease in serum cortisol levels (possibly due to the effect of somatropin on protein transporters);
• immune reactions: rashes on the skin, general manifestations of hypersensitivity, and the development of antibodies against somatropin;
• kidney and urinary system: the emergence of infections in the urinary duct, as well as the development of hematuria;
• Gastrointestinal reactions: pancreatitis, as well as vomiting or nausea;
• reactions of the visual organs: a vision disorder;
• manifestations at the site of introduction and systemic disorders: for adults, violations are most typical due to imbalance of fluids (among them sensation of weakness, peripheral puffiness and leg pastness). Such disorders usually have a moderate or mild severity, occur during the initial months of therapy and pass on their own or after lowering the dosage of drugs. The frequency of such reactions depends on the age of the treatment, the size of the dose of the medicine, and in addition, there is a possibility that it is inversely proportional to the age when the somatotropin deficiency appeared. In children, such complications develop rarely;
• children with Ulrich syndrome: development of respiratory pathologies (otitis media, influenza, tonsillitis with sinusitis and nasopharyngitis) or infections in the urinary duct;
• Adults with a deficiency of STH: the appearance of headaches, weakness, pain in the back or limbs (also a feeling of stiffness), and besides hypoesthesia;
• manifestation in the field of injection (this includes changes in the volume of fatty tissues): burning or pain after the procedure, rashes and itching, the appearance of bleeding, nodules, pigmentation and inflammation with fibrosis.

Myositis develops unilaterally (it is possible that it appears due to the influence of the preservative of meta-cresol, which is an integral component of Rastan). The onset of severe pain or myalgia in the area of administration may result from myositis. With such a violation, Rastan should be replaced with another drug with somatropin, but in which there is no metarecone. Further therapy is carried out, taking into account the ratio of benefit and risk.

There may also be problems such as nighttime apnea syndrome, insomnia, worsening symptoms of existing psoriasis, increased blood pressure, and increased occurrence of moles.

[19], [20], [21]

Overdose

With an acute form of overdose, it is possible to develop hypoglycemia, which then develops into hyperglycemia. Continuous excess dosage can cause acromegaly or gigantism.

[27], [28]

Interactions with other drugs

GKS can inhibit the drug effect of somatropin. If it is necessary to perform HRT, you need to carefully monitor dosages and compliance - in order to prevent the risk of developing adrenal insufficiency or inhibiting the effect of stimulating growth.

Somatropin is a stimulant of activity of hemoprotein P450 (CYP). Because of this, it is capable of lowering plasma parameters (and, correspondingly, weakening the effectiveness) of drugs that are metabolized by the hemoprotein CYP3A. Among such drugs - corticosteroids, sex hormones, anticonvulsants and cycloserine.

Since STH can provoke resistance against insulin, it is required to monitor the presence of diabetes symptoms in the patient or a decrease in glucose tolerance. Also, during therapy with somatotropin, you need to closely monitor the condition of people who already have diabetes or a decreased tolerance for glucose.

Combined use together with GCS can reduce the effects of somatropin. People with ACTH deficiency are required to have HRT, carefully choosing the dosages of GCS - to avoid overwhelming effects on STH.

[29]

Storage conditions

Rastan should be kept in a place that is closed from sunlight and inaccessible to children. Do not freeze the medicine. Temperature indices are within 2-8 ° С.

Shelf life

Rastan is suitable for use in the period of 2 years from the date of release of the medicine. The finished solution can be stored for a maximum of 15 days.

[30]