Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Evolus Pharma Ltd, 70 Sir John Rogersons Quay, Dublin 2, Ireland
NUCEIVA is indicated for the temporary improvement in the appearance of moderate to severe vertical lines between the eyebrows seen at maximum frown (glabellar lines), when the severity of the above facial lines has an important psychological impact in adults below 65 years of age.
NUCEIVA should only be administered by physicians with appropriate qualifications and expertise in the treatment of glabellar lines and the use of required equipment.
The recommended injection per muscle site is 4 U/0.1 mL. Five injection sites (see Figure 1): 2 injections in each corrugator muscle (inferior medial and superior medial aspect) and 1 injection in the procerus muscle for a total dose of 20 Units.
Botulinum toxin units are not interchangeable from one product to another. Doses recommended are different from other botulinum toxin preparations.
In the absence of adverse reactions during the initial treatment, an additional course of treatment can be performed subject to a minimum interval of 3 months between the initial and repeat treatment.
In the event of treatment failure (no visible improvement of glabellar lines at maximum frown) one month after the first course of treatment, the following approaches may be considered:
Examination of the causes of failure, e.g. inappropriate injection technique, incorrect muscles injected, and formation of botulinum toxin-neutralising antibodies.
Re-evaluation of the appropriateness of treatment with botulinum toxin type A.
The efficacy and safety of repeat injections beyond 12 months has not been evaluated.
There are limited clinical data with NUCEIVA in patients older than 65 years (see section 5.1). NUCEIVA is not recommended for use in patients over 65 years of age.
No specific dose adjustment is required for use in the elderly.
There is no relevant use of NUCEIVA in the paediatric population.
Intramuscular use.
Once reconstituted, NUCEIVA should only be used to treat a single patient, during a single session.
For instructions for use, precaution before manipulating or administering the product, handling and disposal of the vials, see section 6.6.
Care should be taken to ensure that NUCEIVA is not injected into a blood vessel when it is injected in the vertical lines between the eyebrows seen at maximum frown (also known as glabellar lines) (see section 4.4).
Physical manipulation (such as rubbing) of the injection site in the immediate post-administration period should be avoided.
Reconstituted NUCEIVA (50 Units/1.25 mL; 100 Units/2.5 mL) is injected using a sterile 30 gauge needle.
In order to reduce the complication of eyelid ptosis the following steps should be taken:
Figure 1. Injection Points:
Signs of overdose may not be apparent immediately post-injection. Should accidental injection or ingestion occur, the patient should be medically monitored for several days for signs and symptoms of general weakness or muscle paralysis. Admission to hospital should be considered in patients presenting with symptoms of botulinum toxin type A poisoning (generalised weakness, ptosis, diplopia, swallowing and speech disorders, or paresis of the respiratory muscles).
Too frequent or excessive dosing may enhance the risk of antibody formation. Antibody formation may lead to treatment failure.
Overdose of NUCEIVA depends upon dose, site of injection, and underlying tissue properties. No cases of systemic toxicity resulting from accidental injection of botulinum toxin type A have been observed. Excessive doses may produce local or distant generalised and profound neuromuscular paralysis. No cases of ingestion of botulinum toxin type A have been reported.
In the event of overdose the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis. Symptomatic treatment should be instigated if necessary
Unopened vial:
50 Units: 24 months.
100 Units: 30 months.
Reconstituted solution:
Chemical and physical in-use stability has been demonstrated for 72 hours at 2-8°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2° to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.
Store in a refrigerator (2°C-8°C).
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Vial (Type I glass) fitted with a stopper (chlorobutyl rubber) and a seal (aluminium).
Pack size of one.
Reconstitution should be performed in accordance with aseptic technique principles. NUCEIVA is reconstituted with sodium chloride 9 mg/ml (0.9%) solution for injection. As per the dilution table below, the amount of sodium chloride 9 mg/ml (0.9%) solution for injection is drawn up into a syringe in order to obtain a reconstituted solution at a concentration of 4 Units/0.1 mL.
| 50 Unit vial | 100 Unit vial | |
|---|---|---|
| Amount of solvent added (sodium chloride 9 mg/ml (0.9%) solution for injection) | 1.25 mL | 2.5 mL |
| Resulting dose (Units per 0.1 mL) | 4 Units | 4 Units |
The central part of the rubber cap should be cleaned with alcohol.
The solution is prepared by injecting the solvent slowly into the vial with a needle through the rubber stopper and by gently rotating the vial avoiding bubble formation. The vial has to be discarded if the vacuum does not pull the solvent into the vial. Once reconstituted, the solution should be visually inspected prior to use. Only clear, colorless solution without particles should be used.
Reconstituted NUCEIVA (50 Units/1.25 mL ; 100 Units/2.5 mL) is injected using a sterile 30 gauge needle. Four Units (4 U/ 0.1 mL) are administered in each of the 5 injection sites (see Figure 1): 2 injections in each corrugator muscle (inferior medial and superior medial aspect) and 1 injection in the procerus muscle for a total dose of 20 Units.
It is mandatory that NUCEIVA is used for one single patient treatment only during a single session.
Immediately after use, and prior to disposal, unused reconstituted NUCEIVA solution in the vial and/or the syringe must be inactivated, with 2 mL of dilute sodium hypochlorite solution at 0.5% or 1% (Javel solution) and should be disposed of in accordance with local requirements.
Used vials, syringes, and materials should not be emptied and must be discarded into appropriate containers and disposed as a Medical Biohazardous Waste in accordance with local requirements.
In the event of an accident when handling the product, whether in the vacuum-dried state or reconstituted, the appropriate measures described below must be initiated immediately.
If splashed into the eyes, rinse eyes thoroughly with plenty of water or with an eye wash solution.
If the injector injures himself (cuts, pricks himself), proceed as above and take the appropriate medical steps.
These instructions for use, handling, and disposal should be strictly followed.
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