Source: Health Products Regulatory Authority (IE) Revision Year: 2019 Publisher: Allergan Pharmaceuticals International Limited, Clonshaugh Business & Technology park, Dublin 17, D17 E400, Ireland
To be administered only by subcutaneous route.
Do not inject within 1 to 1.5 cm of vulnerable anatomic structures.
Belkyra should not be injected into or in close proximity to the marginal mandibular branch of the facial nerve to avoid the potential for motor neuropraxia, which manifests as an asymmetric smile or facial muscle weakness. In the clinical trials, nerve injury was temporary and all cases resolved.
Care should be taken to avoid inadvertent intradermal or intramuscular injection. Belkyra should be injected mid-way into the preplatysmal subcutaneous fat tissue in the submental area. Inappropriate injection techniques such as superficial injections, injections into blood vessels and injections without the skin marking grid, may result in skin ulceration and necrosis. During injection the needle should not be withdrawn from the subcutaneous fat, as this could increase the risk of intradermal exposure and potential skin ulceration and necrosis. Belkyra should never be re-administered if injection site ulceration or injection site necrosis occurs.
Avoid injection into salivary glands, the thyroid gland, lymph nodes and muscles.
The safe and effective use for Belkyra outside the SMF area or at higher than recommended doses has not been established. Belkyra should not be used in patients that are obese (BMI ≥30) or in patients who have body dysmorphic disorder.
Patients should be screened for other potential causes of submental convexity/fullness (e.g. thyromegaly and cervical lymphadenopathy) prior to use of Belkyra.
Caution should be used when Belkyra is administered in the presence of inflammation or induration at the proposed injection site(s) or in patients with symptoms of dysphagia.
Caution should be used when Belkyra is administered in patients who have had prior surgical or aesthetic treatment of the submental area. Changes in anatomy/landmarks or the presence of scar tissue may impact the ability to safely administer
Belkyra or to obtain the desired result.
The clinical studies of Belkyra did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients; therefore, caution should be exercised with these patients.
This medicinal product contains 184 µmol (or 4.23 mg) sodium per mL. To be taken into consideration by patients on a controlled sodium diet.
No clinical drug interaction studies have been conducted with Belkyra.
Reproduction studies have been performed in rats and rabbits at exposures up to 1.8 times (rat) and 12 times (rabbit) the exposure at maximum recommended human dose. While they do not indicate direct or indirect harmful effects with respect to reproductive toxicity, inconclusive findings of missing intermediate lung lobe was noted in rabbits in the embryo-fetal toxicity study (see section 5.3).
There are no adequate and well-controlled studies in pregnant women. As a precautionary measure, it is preferable to avoid the use of Belkyra during pregnancy.
There is no information available on the presence of deoxycholic acid in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because studies in nursing mothers have not been conducted, caution should be exercised when Belkyra is administered to a nursing woman.
There are no clinical data on fertility. Belkyra did not affect general reproductive performance or fertility in male or female rats at doses up to 50 mg/kg, corresponding to approximately 5- and 3-fold exposure margins, respectively, to the maximum human recommended dose (see section 5.3).
No studies on the effects on the ability to drive and use machines have been performed.
The data described in the underlying table reflect undesirable effects reported for Belkyra treated patients who were evaluated in the clinical studies that assessed the use of Belkyra for the treatment of submental fat.
The following side effects have been evaluated in clinical studies with the following frequencies:
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).
Common: Headache
Uncommon: Dysgeuisia
Uncommon: Dysphonia
Common: Dysphagia, nausea
Common: Skin tightness
Very Common: Injection site: Pain, oedema, swelling, anaesthesia, nodule, haematoma, paraesthesia, induration, erythema, pruritus
Common: Injection site: Haemorrhage, discomfort, warmth, discolouration
Uncommon: Injection site: Alopecia, urticaria, ulcer, hypersensitivity
Not known: Injection site; Hypoaesthesia, necrosis*, artery necrosis
Common: Injection site nerve injury
* Adverse reactions related to injection site necrosis were reported as fat necrosis, necrosis, skin necrosis and soft tissue necrosis. These events occurred around the treatment area with affected area ranging between 0.5 cm and 3 cm. In rare cases, the entire submental area was affected.
Overall, the majority of adverse reactions resolved within the treatment interval. The following table presents adverse reactions that have been reported to last longer than the injection intervals of 4 weeks, based on results from the four phase 3 studies (N=758) in Belkyra treated patients.
| Adverse Reactions | BELKYRA | Mean Time to Resolutiona (Range) |
|---|---|---|
| Injection site nerve injury | 3.6% | 53 days (1-334 days) |
| Injection site induration | 23.4% | 41 days (1-292 days) |
| Injection site nodule | 12.0% | 48 days (1-322 days) |
| Injection site pain | 74.1% | 12 days (1-333 days) |
| Injection site sensory symptoms | 66.4% | 46 days (1-349 days) |
| Injection site anaesthesia | 61.6% | 50 days (1-349 days) |
| Injection site paraesthesia | 11.3% | 27 days (1-297 days) |
| Injection site swelling | 78.6% | 15 days (1-218 days) |
| Dysphagia | 1.5% | 22 days (1-142 days) |
a Pertaining to BELKYRA group only
In the clinical studies, some of the local reactions, such as induration, nodule, anaesthesia, pain and swelling at the injection site, and injection site motor nerve injury, were reported as not recovered within the duration of the clinical studies.
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: HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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