Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Evolus Pharma Ltd, 70 Sir John Rogersons Quay, Dublin 2, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Generalised disorders of muscle activity (e.g. myasthenia gravis or Eaton Lambert Syndrome).
Infection or inflammation at the proposed injection sites.
The anatomy and anatomical land marks of procerus corrugator supercilli muscles and the surrounding vasucular and nervous structures in the glabellar region must be understood prior to administration of NUCEIVA. Injection into vulnerable anatomical structures, such as nerves and blood vessels, must be avoided.
Localised pain, inflammation, paraesthesia, hypoaesthesia, tenderness, swelling/oedema, erythema, localised infection, bleeding and/or bruising have been associated with the injection. Needle-related pain and/or anxiety have resulted in vasovagal responses, including transient symptomatic hypotension and syncope.
Caution should be taken when the targeted muscle shows pronouced weakness or atrophy.
Care should be taken to ensure that NUCEIVA is not injected into a blood vessel when it is injected in the glabellar lines seen at maximum frown (see section 4.2).
There is a risk of eyelid ptosis following treatment (see section 4.2).
Caution should be taken if complications have resulted with previous botulinum toxin injections.
Caution should be exercised when NUCEIVA is used in patients with bleeding disorders as injection may lead to bruising.
Adverse reactions possibly related to the spread of toxin distant from the site of administration have been reported very rarely with botulinum toxin (see section 4.8). Swallowing and breathing difficulties are serious and can result in death. Injection of NUCEIVA is not recommended in patients with a history of dysphagia and aspiration.
Patients or caregivers should be advised to seek immediate medical care if swallowing, speech or respiratory disorders arise.
Patients with unrecognised neuromuscular disorders may be at increased risk of clinically significant systemic effects, including severe dysphagia and respiratory compromise from typical doses of botulinum toxin type A. In some of these cases, dysphagia has lasted several months and required placement of a gastric feeding tube (see section 4.3).
Caution should also be exercised when botulinum toxin type A is used for treatment of patients with amyotrophic lateral sclerosis or with peripheral neuromuscular disorders.
An anaphylactic reaction may occur very rarely after injection of botulinum toxin. Epinephrine (adrenaline) or any other anti-anaphylactic measures should therefore be available.
Antibodies to botulinum toxin type A may develop during treatment with botulinum toxin. Some of the antibodies formed are neutralising which may lead to treatment failure of botulinum toxin type A.
It is mandatory that NUCEIVA is used for one single patient treatment only during a single session.
No interaction studies have been performed.
Theoretically, the effect of botulinum toxin may be potentiated by aminoglycoside antibiotics, spectinomycin, or other medicinal products that interfere with neuromuscular transmission (e.g. neuromuscular blocking medicinal products).
The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
There are no adequate data from the use of botulinum toxin type A in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). NUCEIVA is not recommended during pregnancy and in women of childbearing potential not using contraception.
There is no information on whether NUCEIVA is excreted in human breast milk. NUCEIVA should not be used during breast-feeding.
The effect of NUCEIVA on human fertility is unknown. However, another botulinum toxin type A has been shown to impair the fertility of male and female animals.
NUCEIVA has a minor or moderate influence on the ability to drive and use machines. There is a potential risk for asthenia, muscle weakness, dizziness and visual disturbance, which could affect driving and the operation of machinery.
Serious undesirable effects that may occur following treatment with NUCEIVA include eyelid ptosis, an immune response, distant spread of toxin, development or exacerbation of a neuromuscular disorder, and hypersensitivity reactions. The most commonly reported adverse effects during treatment are headache, occurring in 9.0% of patients, followed by eyelid ptosis, occurring in 1.0% of patients.
The NUCEIVA related adverse reactions are classified by System Organ Class and frequency defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Table 1:
| System Organ Class | Preferred Term | Frequency |
|---|---|---|
| Infections and infestations | Upper respiratory tract infection | Rare |
| Psychiatric disorders | Depression | Rare |
| Nervous system disorders | Headache | Common |
| Dizziness, migraine, muscle tone disorder, speech disorder | Uncommon | |
| Dysaesthesia, head discomfort, hypoaesthesia, paraesthesia, sensory disturbance | Rare | |
| Eye disorders | Eyelid ptosis | Common |
| Asthopenia, blepharospasm, brow ptosis, eyelid oedema, eye swelling, vision blurred | Uncommon | |
| Diplopia, dry eye, eyelid sensory disorder | Rare | |
| Ear and labyrinth disorders | Vertigo | Rare |
| Vascular disorders | Flushing | Rare |
| Respiratory, thoracic and mediastinal disorders | Epistaxis | Rare |
| Gastrointestinal disorders | Diarrhea | Rare |
| Skin and subcutaneous tissue disorders | Pruritis | Uncommon |
| Dermal cyst, erythema, photosensitivity reaction, skin mass, skin tightness | Rare | |
| Musculoskeletal and connective tissue disorders | Muscle twitching, musculoskeletal pain, myalgia, neck pain | Rare |
| General disorders and administration site conditions | Application site bruising, influenza like illness, injection site bruising, injection site pain, injection site swelling | Common |
| Injection site: erythema, injection site paresthesia, injection site pruritis, pain, tenderness | Rare | |
| Investigations | Intraocular pressure test | Rare |
| Injury, poisoning and procedural complications | Contusion | Uncommon |
| Post-procedural swelling, procedural headache | Rare |
Note: Of the 1659 subjects treated with NUCEIVA, rare events occurred in 1 subject only. Uncommon events occurred in between 2 and 7 subjects.
Application related undesirable effects that have been reported following administration of NUCEIVA are uncommon events individually, common when added together. These include application and injection site bruising, injection site pain and injection site swelling. Rarely occurring injection site events that have been reported include erythema, paraesthesia, pruritis, pain and tenderness.
Muscle atrophy is expected after repeated botulinum treatment secondary to the flaccid paralysis of the treated muscles.
Adverse reactions possibly related to the spread of toxin distant from the site of administration have been reported very rarely with botulinum toxin (e.g. muscle weakness, breathing difficulties, dysphagia or constipation) (see section 4.4).
An anaphylactic reaction may occur very rarely after injection of botulinum toxin. Epinephrine (adrenaline) or any other anti-anaphylactic measures should therefore be available.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
