Spinraza
Spinraza: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Semprex
ATX code: M09AX07
Active ingredient: nusinersen (Nusinersen)
Manufacturer: Wetter Pharma-Fertigung, GmbH & Co. KG (Vetter Pharma-Fertigung, GmbH & Co. KG) (Germany); Pateon Italia, S.p. A. (Patheon Italia, SpA) (Italy)
Description and photo update: 2020-01-03
Spinraza is the newest drug for the treatment of diseases of the musculoskeletal system.
Release form and composition
The drug is produced in the form of a solution for intrathecal (endolumbar) administration: colorless, transparent liquid, free from undissolved particles (5 ml each in glass vials, sealed with a rubber stopper and an aluminum cap, closed with a plastic lid; in a cardboard box 1 bottle and instructions for use of Spinraza).
Composition for 1 ml of solution:
- active substance: nusinersen (in the form of nusinersen sodium) - 2.4 mg;
- auxiliary components: anhydrous disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, potassium chloride, magnesium chloride hexahydrate, sodium chloride, 1M hydrochloric acid solution, calcium chloride dihydrate, 1M sodium hydroxide solution, water for injection.
Pharmacological properties
Pharmacodynamics
Spinraza is an antisense oligonucleotide (ASO). Its structure is specially designed for the treatment of a rare progressive neuromuscular disease with an autosomal recessive mode of inheritance - SMA (spinal muscular atrophy). SMA is caused by mutations in the long arm of chromosome 5 (5q), which lead to the loss of function of a special gene responsible for the survival of motor neurons (gene SMN1). As a result of insufficient function of this gene, a deficiency of the SMN protein occurs. Despite the fact that the SMN2 gene is also responsible for the formation of this protein, the total amount of SMN protein remains low (since the amount of synthesized SMN protein under the influence of the SMN2 gene is insignificant).
SMA refers to the spectrum of different clinical conditions. The severity of the disease depends on the number of copies of the SMN2 gene and the age of onset.
The mechanism of action of Spinraza is associated with an increase in the proportion of mRNA (template ribonucleic acid) transcripts with the inclusion of exon 7 of the SMN2 gene. mRNA is translated into the full-chain SMN protein, thereby maintaining the functional activity of the protein.
Pharmacokinetics
After nusinersen injection, the drug is completely distributed throughout the CSF (cerebrospinal fluid). The targets of the therapeutic action of Spinraza are the tissues of the central nervous system (central nervous system).
After repeated administration, the average minimum residual concentrations of the active substance in the CSF increased by about 1.4–3 times. The equilibrium state was reached within approximately 24 months. Additional injections of the drug after reaching an equilibrium state do not lead to further accumulation of nusinersen in the tissues of the central nervous system or CSF.
After the administration of Spinraza, the minimum residual plasma concentrations were relatively low (when compared with the residual concentrations in the CSF). The increase in mean values of maximum plasma concentration and AUC (area under the concentration-time curve) was proportional to the administered dose. Multiple injections did not lead to cumulation.
Nusinersen is widely distributed in the central nervous system, reaching therapeutic concentrations in the tissues of the spinal cord, which represent a therapeutic target. It has also been shown that the drug is present in neurons and other cells of the brain and spinal cord and peripheral tissues (including the kidneys, liver and skeletal muscles).
It is metabolized by hydrolysis, which is mediated by exonucleases 3 'and 5'. Nusinersen is not an inducer or inhibitor, nor is it a substrate for cytochrome P450 enzymes.
The main route of elimination of the drug and its metabolites is, apparently, excretion in the urine. The terminal half-life of nusinersen from CSF is 135–177 days on average.
The patient's gender does not affect the pharmacokinetics of Spinraza.
Indications for use
Spinraza is used to treat a rare genetic disorder called SMA (spinal muscular atrophy).
Contraindications
The drug is contraindicated in patients with increased individual sensitivity to the main or auxiliary components.
Spinraza, instructions for use: method and dosage
Spinraz solution is injected intrathecally, through lumbar puncture. Treatment can only be carried out by specialists with experience in performing lumbar puncture.
Therapy should be started as early as possible after diagnosis. The recommended single dose of Spinraza is 5 ml (12 mg). The drug is administered on the 1st day of treatment (day 0) and then on the 14th, 28th and 63rd days of treatment. If the next dose is delayed or missed, the drug is administered as early as possible (the interval between two doses should be at least 14 days).
In the future, Spinraza is administered once every 4 months. If the next injection is missed or delayed, the solution should be injected as early as possible, and then continue the administration at the set frequency.
Spinraza must be used for a long time and constantly. The advisability of continuing therapy is assessed by the attending physician.
Instructions for preparation and dose administration:
- Before the administration of the drug, the condition of the solution should be visually assessed. It should be colorless and transparent and not contain any particles.
- The preparation of the solution and its further administration should be carried out under aseptic conditions.
- Immediately before administration, you should take the bottle out of the refrigerator and keep it for some time at room temperature. External heat sources must not be used.
- An unopened and unused bottle can be returned to the refrigerator if it has been at a temperature of up to 25 ° C for no more than 30 hours.
- Before the introduction, the rubber stopper of the vial is pierced with a needle and the required volume of solution is drawn into the syringe. Additional dilution is not required. If the collected solution is not used for 6 hours, it must be disposed of.
- In some cases, with the introduction of the drug, sedation may be required (carried out according to indications, taking into account the clinical condition of the patient).
- With the intrathecal administration of Spinraza injections, especially in early age groups and patients with scoliosis, it is advisable to use any imaging (for example, ultrasound) control.
- Before injecting the solution, it is recommended to extract a volume of CSF equivalent to the injected volume of the drug.
- Spinraza is injected intrathecally in a bolus over 1–3 min. A spinal anesthesia needle must be used to inject the drug. It is impossible to inject in places where there are signs of an inflammatory or infectious process on the skin.
- The unused amount of solution should be disposed of.
The safety and efficacy of Spinraza was studied in children 0-17 years old. In patients aged 18 years and older, experience with the drug is limited. There is no experience with the use of nusinersen in persons over 65 years of age.
In patients with impaired renal and / or liver function, the use of the drug has not been studied.
Side effects
All unwanted side effects of Spinraza are associated with the lumbar puncture procedure and can be regarded as symptoms of post-dural puncture syndrome:
- digestive system: very often - vomiting;
- nervous system: very often - headache;
- musculoskeletal system and connective tissue: very often - back pain.
During the period of post-registration use of Spinraza, such serious side effects as meningitis and hydrocephalus were recorded, which are most likely due to the method of administration of the drug (lumbar puncture).
In the populations of infants in whom the drug is used most often, some undesirable side effects, for example, back pain and headache, cannot be evaluated, which is associated with the limited communication capabilities of patients in this group.
The immunogenicity of the drug is low. There was no significant effect of the formation of antidrug antibodies on the clinical response, pharmacokinetics, or side effects of nusinersen.
Overdose
Overdose cases have not been registered. If you experience any adverse reactions to Spinraza, you should seek medical attention.
special instructions
Sometimes after intravenous or subcutaneous administration of other ASOs, blood clotting disorders and thrombocytopenia were observed. If there are clinical indications, it is recommended to perform the necessary laboratory tests to determine blood clotting and platelet counts before the administration of Spinraza.
Other ASOs caused nephrotoxicity, therefore, in the presence of clinical indications, it is recommended to determine the protein content in morning urine. If the protein in the urine is consistently elevated, further testing should be done.
Cases of hydrocephalus not associated with bleeding and meningitis have been reported in patients who received nusinersen. Some patients received a ventriculoperitoneal shunt. In individuals with reduced consciousness, it is necessary to assess the likelihood of developing hydrocephalus. To date, the risks and benefits of treatment with Spinraza in patients with ventriculoperitoneal shunt are unknown, therefore, the feasibility and need for further therapy should be carefully evaluated.
Influence on the ability to drive vehicles and complex mechanisms
There is no data.
Application during pregnancy and lactation
Studies of the drug during pregnancy and breastfeeding have not been conducted. The introduction of Spinraza injections to women of reproductive age or pregnant women is possible after assessing the ratio of the expected benefit and potential risk.
In experiments carried out on animals, no effect of nusinersen on the fertility of females or males, reproductive organs, as well as the growth and development of the fetus was found.
Pediatric use
In children from birth to 17 years of age, Spinraza is used according to indications and in recommended doses.
With impaired renal function
In case of impaired renal function, the use of the drug has not been studied.
For violations of liver function
The use of Spinraza in persons with impaired liver function has not been studied.
Drug interactions
No special clinical studies have been conducted to determine drug interactions of nusinersen with other drugs. The likelihood of such interactions is very small, since nusinersen is neither an inducer nor an inhibitor of cytochrome P450 enzymes and is not metabolized with the participation of these enzymes.
Analogs
There is no information about Spinraza's analogues.
Terms and conditions of storage
Store in a dark place, out of the reach of children, in the original packaging at a temperature of + 2 … + 8 ° C. The solution must not be frozen.
It is allowed to store the drug in its original packaging (in a cardboard box) at room temperature no more than 30 ° C for no more than 14 days. If during this time the solution has not been used, repeated storage in the refrigerator (at a temperature of + 2 … + 8 ° C) is unacceptable.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Spinraz
There are very few reviews of Spinraz, since the drug is new and registered in Russia relatively recently. This is the first drug registered in the country to slow the development of a rare genetic disease - spinal muscular atrophy. In Russia, there are more than 800 people with this diagnosis.
Spinraza price in pharmacies
The selling price for Spinraza has not yet been set. It is one of the most expensive drugs in the world. In the USA the cost of one bottle reaches 125 thousand dollars.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
