AZZALURE Powder for solution for injection Ref.[27680] Active ingredients: Botulinum toxin type A

Care should be taken to ensure that Azzalure is not injected into a blood vessel.

Pre-existing Neuromuscular Disorders

Azzalure should be used with caution in patients with a risk of, or clinical evidence of, marked defective neuro-muscular transmission. Such patients may have an increased sensitivity to agents such as Azzalure, which may result in excessive muscle weakness.

Injection of Azzalure is not recommended in patients with a history of dysphagia and aspiration.

Local and distant spread of toxin effect

Adverse reactions possibly related to the spread of toxin distant from the site of administration have been reported very rarely with botulinum toxin. Patients treated with therapeutic doses may experience exaggerated muscle weakness. Swallowing and breathing difficulties are serious and can result in death.

Patients or care-givers should be advised to seek immediate medical care if swallowing, speech or respiratory difficulties arise.

The recommended dose and frequency of administration for Azzalure must not be exceeded.

It is essential to study the patient’s facial anatomy prior to administering Azzalure. Facial asymmetry, ptosis, excessive dermatochalasis, scarring and any alterations to this anatomy, as a result of previous surgical interventions should be taken into consideration.

Caution should be taken when Azzalure is used in the presence of inflammation at the proposed injection site(s) or when the targeted muscle shows excessive weakness or atrophy.

As with all intramuscular injections, Azzalure treatment is not recommended in patients who have a prolonged bleeding time.

Antibody formation

Injections at more frequent intervals or at higher doses can increase the risk of antibody formation to botulinum toxin. Clinically, the formation of neutralising antibodies may reduce the effectiveness of subsequent treatment.

The effect of administering different botulinum neurotoxins during the course of treatment with Azzalure is unknown and must be avoided.

It is mandatory that Azzalure is used for one single patient treatment only during a single session. The excess of unused product must be disposed of as detailed in section 6.6. Particular precautions should be taken for product preparation and administration as well as for the inactivation and disposal of the remaining unused solution (see section 6.6).

Concomitant treatment of Azzalure and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents) should only be used with caution since the effect of botulinum toxin type A may be potentiated.

No interaction studies have been performed. No other interactions of clinical significance have been reported.

Pregnancy

Azzalure should not be used during pregnancy. There are no adequate data from the use of botulinum toxin type A in pregnant women. Studies in animals have shown reproductive toxicity at high doses (see section 5.3). The potential risk for humans is unknown.

Breast-feeding

There is no information on whether Azzalure is excreted in human milk. The use of Azzalure during lactation cannot be recommended.

Fertility

There are no clinical data from the use of Azzalure on fertility. There is no evidence of direct effect of Azzalure on fertility in animal studies (see section 5.3).

Azzalure has a minor or moderate influence on the ability to drive and use machines. There is a potential risk of localised muscle weakness or visual disturbances linked with the use of this medicinal product which may temporarily impair the ability to drive or operate machinery.

Approximately 3800 patients were exposed to Azzalure in the different clinical trials.

Based on placebo-controlled clinical trials, the observed rates of adverse reactions after the first injection of Azzalure were 22.3% for the treatment of glabellar lines (16.6% for placebo) and 6.2% for the treatment of lateral canthal lines (2.9% for placebo). Most of these adverse reactions were of mild to moderate severity and reversible.

The most frequent undesirable reactions were headache and injection site reactions for glabellar lines and headache, injection site reactions and eyelid oedema for lateral canthal lines. In general, treatment/injection technique related reactions occurred within the first week following injection and were transient. The incidence of treatment/injection technique related reactions decreased over repeat cycles. Undesirable effects may be related to the active substance, the injection procedure, or a combination of both.

The safety profile of Azzalure for concomitant treatment of glabellar lines and lateral canthal lines was evaluated in the open label part of the phase III study; the nature and frequency of adverse reactions were comparable to what was observed when patients were treated for the individual indications.

The frequency of undesirable reactions is classified 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); not known (cannot be estimated from the available data).

For glabellar lines:

Nervous system disorders

Very Common: Headache

Common: Temporary facial paresis (due to temporary paresis of facial muscles proximal to injection sites, predominantly describes brow paresis)

Uncommon: Dizziness

Eye disorders

Common: Asthenopia, Eyelid ptosis, Eyelid oedema, Lacrimation increased, Dry eye, Muscle twitching (twitching of muscles around the eyes)

Uncommon: Visual impairment, Vision blurred, Diplopia

Rare: Eye movement disorder

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, Rash

Rare: Urticaria

General disorders and administration site conditions

Very Common: Injection site reactions (e.g. erythema, oedema, irritation, rash, pruritus, paraesthesia, pain, discomfort, stinging and haematoma)

Immune system disorders

Uncommon: Hypersensitivity

For lateral canthal lines:

Nervous system disorders

Common: Headache, Temporary facial paresis (temporary paresis of facial muscles proximal to injection sites)

Eye disorders

Common: Eyelid oedema, Eyelid ptosis

Uncommon: Dry eye

General disorders and administration site conditions

Common: Injection site reactions (e.g. haematoma, pruritus and oedema)

Adverse reactions resulting from distribution of the effects of the toxin to sites remote from the site of injection have been very rarely reported with botulinum toxin (excessive muscle weakness, dysphagia, aspiration pneumonia with fatal outcomes in some cases) (see section 4.4).

Post-marketing experience

Nervous system disorders

Not known: Hypoaesthesia

Reporting of suspected adverse reactions

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 Yellow Card Scheme.

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.