NUCEIVA

NUCEIVA should only be administered by healthcare practitioners with appropriate qualifications and expertise in the treatment of glabellar lines and the use of required equipment. 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.

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.

1). This medicine is not recommended for use in patients over 65 years of age. No specific dose adjustment is required for use in the elderly. Paediatric population There is no relevant use of this medicine in the paediatric population.

Method of administration Intramuscular use. Once reconstituted, NUCEIVA should only be used to treat a single patient, during a single session. 6. 4). Physical manipulation (such as rubbing) of the injection site in the immediate post- administration period should be avoided.

25 mL) is injected using a sterile 30 gauge needle. In order to reduce the complication of eyelid ptosis the following steps should be taken: • Two injections should be administered in each corrugator muscle (inferior medial and superior medial aspect) and 1 injection in the procerus muscle for a total dose of 20 Units.

• Injection near the levator palpebrae superioris should be avoided, particularly in patients with larger brow depressor complexes. • Lateral corrugator injections should be placed at least 1 cm above the bony supraorbital ridge.

Summary of the safety profile Serious adverse reactions that may occur following treatment with this medicine include eyelid ptosis, an immune response, distant spread of toxin, development or exacerbation of a neuromuscular disorder, and hypersensitivity reactions.

0% of patients, followed by eyelid ptosis, occurring in 1% of patients. Tabulated list of adverse reactions Table 1 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).

System organ class Preferred term Frequency Infections and infestations Upper respiratory tract infection Rare Psychiatric disorders Depression Rare Headache Common Dizziness, migraine, muscle tone disorder, speech disorder Uncommon Nervous system disorders Dysaesthesia, head discomfort, hypoaesthesia, paraesthesia, sensory disturbance Rare Eyelid ptosis Common Asthopenia, blepharospasm, brow ptosis, eyelid oedema, eye swelling, vision blurred Uncommon Eye disorders 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 Pruritis UncommonSkin and subcutaneous tissue disorders 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 Contusion UncommonInjury, poisoning and procedural complications Post-procedural swelling, procedural headache Rare Note: Of the 1659 subjects treated with NUCEIVA, rare events occurred in 1 subject only.

General 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 this medicine. 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 pronounced weakness or atrophy. 2). 2). Caution should be taken if complications have resulted with previous botulinum toxin injections. Bleeding disorders Caution should be exercised when this medicine is used in patients with bleeding disorders as injection may lead to bruising.

8). Swallowing and breathing difficulties are serious and can result in death. Injection of this medicine 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.

Pre-existing neuromuscular disorders 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.

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. Hypersensitivity reactions An anaphylactic reaction may occur very rarely after injection of botulinum toxin.

Epinephrine (adrenaline) or any other anti-anaphylactic measures should therefore be available. Antibody formation 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.

1. g. myasthenia gravis or Eaton Lambert Syndrome) Infection or inflammation at the proposed injection sites.