RADIESSE SIDE EFFECTS

SIDE EFFECTS

Adverse Events

Nasolabial folds pre-market clinical trial

Tables 1-4 contain the adverse events for 117 patients in a randomized, controlled study at 4 US investigational sites. Patients in the study received RADIESSE injectable implant in one side of the face and a collagen dermal implant as the Control in the other side of the face. Adverse events reported in patient diaries during the 14 days after treatment are listed in Tables 1 and 2. Physician reported adverse events are those reported by Investigators and patients any time outside the 2 week diaries. Those adverse events are presented in Tables 3 and 4.

Table 1:  PATIENT DIARY ADVERSE EVENTS
Reported Through Patient Diaries Number of Patients With at Least One Adverse Event By Adverse Event Type N = 117

There were 12 systemic adverse events reported for 9 patients. None of these systemic adverse events were related to either RADIESSE injectable implant or Control and included emergency gallbladder surgery, breast pain, infected and exposed breast implant, gastroenteritis, uterine fibroids, headache, burning and numbness in tongue and lips, tongue ulceration and fatigue.

Table 2: PATIENT DIARY ADVERSE EVENTS
By Adverse Event Type N = 117

Table 3: PHYSICIAN REPORTED ADVERSE EVENTS
Number of Patients With at Least One Adverse Event By Adverse Event Type N = 117

Table 4: PHYSICIAN REPORTED ADVERSE EVENTS
By Adverse Event Type N = 117

Nasolabial Folds Mixing Radiesse Injectable Implant With 2% Lidocaine Hcl Pre-Market Clinical Trial

In a prospective, randomized split-face single-blind clinical study, 50 patients were injected with syringes of 1.3cc of RADIESSE injectable implant mixed with 0.2cc of 2% lidocaine HCl (lidocaine) in one nasolabial fold (Treatment) and RADIESSE injectable implant without the 2% lidocaine (Control) in the contralateral nasolabial fold at two investigational sites in the United States. The purpose of this study was to assess the effectiveness of RADIESSE injectable implant mixed with 2% lidocaine for the reduction of pain during injection and the incidence of adverse events through the 1 month follow-up period.

The adverse events reported during this study were generally expected, mild in nature and short in duration and are detailed in the tables below. Adverse events were reported through patient diaries and by the principal investigators, with the majority of adverse events reported through the patient diaries. Adverse events are presented by time point and in total for the Treatment and Control groups. The majority of adverse events were reported in the ≤ 14 day time period. There was no statistical difference with respect to occurrence of patient diary reported adverse events between the 2 groups (see Table 5). There were 2 adverse events reported by the investigators (depression for one patient and redness for one patient in the Control nasolabial fold).

Table 5: ADVERSE EVENTS REPORTED IN PATIENT DIARIES
N = 50

Nasolabial Folds Long-Term Safety Post-Approval Study

A post approval study was performed to 1) collect long-term safety information on use of RADIESSE injectable implant injected into the nasolabial folds; and 2) to assess the effect of multiple injections. There were no reports of long term adverse events in this post approval study. The adverse events monitored in the post-approval study included allergic reaction, ecchymosis, edema, embolization, erosion, erythema, extrusion, granuloma, hematoma, infection, necrosis, needle jamming, nodule, and pain.

Nasolabial Folds Fitzpatrick Skin Type Iv-Vi Post-Approval Study

Adverse events reported in the short-term Fitzpatrick Skin Type IV-VI post-approval study are presented in Table 6.

Table 6: ADVERSE EVENTS
N = 100

Post Marketing Surveillance

The following adverse events were received from post-marketing surveillance for the RADIESSE injectable implant in the US and outside the US and were not observed in the clinical trials with RADIESSE injectable implant: infection, over-injection, under-injection, loss of effect, product displacement, allergic reaction, necrosis, granuloma, exposed material, hair loss, tingling, ptosis, abscess, paralysis, superficial injection, herpetic infection, hematoma, blanching, blistering, bluish color, dark circles, did not like results, dizziness, double vision, festoons, flu-like symptoms, grey discoloration, Guillain-Barre syndrome, hyperventilating, inflammation, ischemic reaction, lymphoid hyperplasia, nausea, pallor to skin, prior medical condition worsened, pericarditis, possible blood clot, scarring, sensitivity to cold, skin texture changed, tissue mass developed, vascular compromise, and ocular ischemia.

The most commonly reported serious adverse events (with a frequency greater than 5 reported events) were necrosis, allergic reaction, edema, and infection. The following describes these serious adverse events:

• Necrosis was generally preceded by pain and blanching of the skin at the time of injection accompanied with stinging or tingling and bruising, redness, and swelling. Onset of necrosis ranged from immediately at time of injection to 12 days after injection. Treatment for necrosis generally consisted of a combination of nitroglycerin ointment/vasodilatation, ibuprofen, acetaminophen, or aspirin, antibiotics, steroids, non-steroidal wound treatment ointment and warm compresses. For cases where information was available, patients had recovered or were recovering with minimal to no scarring at last contact. Few cases required consultation with a plastic surgeon and possible excision and revision surgery to correct the defect resulting from the necrosis.
• Allergic Reaction was identified by itchiness and severe swelling, including swelling of the face and tongue. Onset ranged from immediately after injection to 2 days after injection. Allergic reaction was generally treated with anti-histamines and steroids. Some cases required hospitalization. All patients recovered from the allergic reaction with no permanent adverse outcome.
• Serious edema has been reported with an onset ranging from 1 day to 3 weeks (inflammation related to nodule formation). Treatment generally consisted of administration of antibiotics, anti-histamines and steroids. In some cases patients sought treatment in an emergency room or were hospitalized. Generally events resolved within 1 to 2 days but a few patients have been reported as having intermittent edema or persistent edema related to a reoccurring infection. For cases where information was available, most patients have recovered or are recovering.
• Infection, often identified as cellulitis, was accompanied by swelling, hardened areas, redness, pustules, and pain. Onset of infection ranged from 1 day to 2 months and generally lasted 2 days but, in one case, persisted for 6 months. Infections were generally treated with antibiotics. For cases where information was available, patients had recovered or were recovering. Few patients experienced scarring that may require corrective surgery or discoloration at the site of the infection.

Individualization Of Treatment

Before treatment, the patient’s suitability for the treatment and the patient’s need for pain relief should be assessed. The outcome of treatment with RADIESSE injectable implant will vary between patients. In some instances, additional treatments may be necessary depending on the size of the defect and the needs of the patient.