Drug Safety-related Labeling Changes (SrLC)

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Xeomin (BLA-125360)

(incobotulinumtoxinA)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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07/05/2024 (SUPPL-99)

5 Warnings and Precautions

5.2 Lack of Unit Equivalency Between Botulinum Toxin Products

Subsection title revised

The potency Units of XEOMIN are specific to the preparation and assay method utilized. Units of biological activity of XEOMIN cannot be compared to or converted into Units of any other botulinum toxin products assessed with any other specific assay method [see Description (11)].

5.8 Pre-existing Conditions at the Injection Site

Additions and/or revisions underlined:

Use caution when XEOMIN is used where the targeted muscle shows excessive weakness or atrophy.

Use caution when XEOMIN is used in patients who have marked facial asymmetry, with surgical alterations to the facial anatomy, pre-existing eyelid or eyebrow ptosis, when excessive weakness or atrophy is present in the target muscles, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin (e.g., the inability to substantially lessen glabellar lines even by physically spreading them apart).

6 Adverse Reactions

Addition and/or revisions underlined:

• Lack of Unit Equivalency between Botulinum Toxin Products [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is XEOMIN?

XEOMIN is a prescription medicine:

…

• improve the appearance of upper facial lines (glabellar lines, horizontal forehead lines, and lateral canthal lines) (treated simultaneously or individually) for a short period of time (temporary) in adults.

  It is not known if XEOMIN is safe and effective in children younger than:

• 2 years of age for the treatment of chronic sialorrhea

• 2 years of age for the treatment of upper limb spasticity

• 18 years of age for the treatment of upper facial lines (glabellar lines, horizontal forehead lines, and lateral canthal lines), cervical dystonia, or blepharospasm

…

The most common side effect of Xeomin in adults with upper facial lines (glabellar lines, horizontal forehead lines, and lateral canthal lines) include:

• injection site bruising

09/08/2023 (SUPPL-97)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Pre-existing Conditions at the Injection Site

Newly added subsection:

Caution should be taken when XEOMIN is used where the targeted muscle shows excessive weakness or atrophy.

08/13/2021 (SUPPL-93)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been reported during post-approval use of XEOMIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: allergic dermatitis, dysarthria, dysphagia, eye swelling, eyelid edema, flu-like symptoms, herpes zoster, hypersensitivity, injection site pain, injection site reaction, localized allergic reactions (e.g., swelling, edema, erythema, pruritus or rash), muscle spasm, muscular weakness, myalgia, nausea, and persistent dry mouth (> 110 days).

12/18/2020 (SUPPL-86)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive changes; please refer to label)

6.2 Immunogenicity

(Additions and/or revisions underlined)

As with all therapeutic proteins, there is a potential for immunogenicity.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.  Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other botulinumtoxinA products may be misleading.

Of the 2649 patients treated with XEOMIN in clinical trials [see Clinical Studies (14)], 9 (0.3%) patients were positive for neutralizing antibodies after treatment whose antibody status at baseline was unknown and 4 (0.2%) additional patients developed neutralizing antibodies after treatment.  No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Chronic Sialorrhea

Chronic Sialorrhea in Adult Patients

Of the 180 patients treated with XEOMIN in the main phase and extension period of the adult chronic sialorrhea clinical trial [see Clinical Studies (14.1)], 1 (0.6%) patient was positive for neutralizing antibodies after treatment.  The patient had an antibody status unknown at baseline, and had not received a botulinum toxin treatment in the 12 months prior to enrollment in the study.  No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Chronic Sialorrhea in Pediatric Patients

Of the 252 patients treated with XEOMIN in the main phase and open-label extension period of the pediatric chronic sialorrhea clinical trial [see Clinical Studies (14.1)], antibody measurements were only performed in patients with body weight of 30 kg or more, resulting in 80 patients tested for antibodies at baseline.  Three patients tested positive for neutralizing antibodies at baseline and remained positive at the end of the study.  No additional patients developed neutralizing antibodies, and none of the patients demonstrated a secondary lack of treatment response.

…

8 Use in Specific Populations

8.4 Pediatric Use

(Additions and/or revisions underlined)

Safety and effectiveness of XEOMIN in patients less than 18 years of age have not been established for lower limb spasticity, cervical dystonia, blepharospasm, or glabellar frown lines [see Warnings and Precautions (5.1)].

Chronic Sialorrhea in Pediatric Patients

The safety and effectiveness of XEOMIN have been established by evidence from an adequate and well-controlled study of XEOMIN in patients 6 to 17 years of age with chronic sialorrhea [See Clinical Studies (14.1)]. Use of XEOMIN in patients 2 to 5 years of age is supported by the findings of efficacy and safety in patients 6 years and older with chronic sialorrhea, and by safety data in patients 2 to 5 years of age. Safety and effectiveness in pediatric patients below the age of 2 years have not been established [see Warnings and Precautions (5.1)].

…

8.5 Geriatric Use

(Additions and/or revisions underlined)

Chronic Sialorrhea

Of the total number of 184 patients in the placebo-controlled study in chronic sialorrhea in adult patients [see Clinical Studies (14.1)], 107 were 65 years of age and over (46 treated with XEOMIN 100 Units, 44 treated with XEOMIN 75 Units, and 17 received placebo).  No differences in safety or effectiveness were observed between older and younger patients. Other clinical studies have not identified differences in responses between older and younger patients, but increased sensitivity in older patients cannot be ruled out.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Additions and/or revisions underlined)

What is XEOMIN?

XEOMIN is a prescription medicine:

• that is injected into glands that make saliva and is used to treat long-lasting (chronic) drooling (sialorrhea) in adults and in children 2 to 17 years of age.

• that is injected into muscles and used to:

• treat increased muscle stiffness in the arm because of upper limb spasticity in adults.

• treat increased muscle stiffness in the arm in children 2 to 17 years of age with upper limb spasticity, excluding spasticity caused by cerebral palsy.

• treat the abnormal head position and neck pain with cervical dystonia (CD) in adults.

• treat abnormal spasm of the eyelids (blepharospasm) in adults.

• improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) for a short period of time (temporary) in adults.

It is not known if XEOMIN is safe and effective in children younger than:

• 2 years of age for the treatment of chronic sialorrhea

• 2 years of age for the treatment of upper limb spasticity

• 18 years of age for the treatment of cervical dystonia, blepharospasm, or glabellar lines

 

...

The most common side effects of XEOMIN in children 2 to 17 years of age with chronic sialorrhea include:

• bronchitis              headache

• nausea                 vomiting

...

08/18/2020 (SUPPL-78)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Spread of Toxin Effect

Additions and/or revisions underlined:

… In unapproved uses, including lower limb spasticity in children, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.

6 Adverse Reactions

6.1 Clinical Trials Experience

Upper Limb Spasticity

Upper Limb Spasticity in Adult Patients

Additions and/or revisions underlined:

Table 6: Adverse Reactions (greater than or equal to 2%) and Greater for XEOMIN than Placebo: Double-Blind Phase of Placebo-Controlled Adult Upper Limb Spasticity Study 1 and Study 2

Upper Limb Spasticity in Pediatric Patients

Table 7 lists the adverse reactions that occurred in greater than or equal to 2% of XEOMIN-treated patients in Study 1 in pediatric patients 2 years of age and older with upper limb spasticity. In the controlled portion of Study 1, 350 patients were randomized to one of three doses of XEOMIN: 87 received 2 Units/kg per affected upper limb, 87 received 6 Units/kg per affected upper limb, and 176 received 8 Units/kg per affected upper limb [see Clinical Studies (14.2)]. XEOMIN-treated patients were 2 to 17 years old (mean 7 years), 63% were male, and 90% were White.

No relationship between increased dose and increased occurrence of adverse reactions was observed. The most common adverse reactions (greater than or equal to3% of XEOMIN-treated patients) at the recommended dose of XEOMIN (8 Units/kg) were nasopharyngitis and bronchitis.

Table 7: Adverse Reactions (greater than or equal to 2%) in Patients Treated with XEOMIN 2 Units/kg or 8 Units/kg: Double-Blind Phase of Study 1 in Pediatric Upper Limb Spasticity Newly added table; please refer to label for complete information.

6.2 Immunogenicity

Additions and/or revisions underlined:

Upper Limb Spasticity

Upper Limb Spasticity in Adult Patients

Of the 456 patients treated with XEOMIN in the main phase and open-label extension period of the adult upper limb spasticity clinical trials (Study 1 and Study 2) [see Clinical Studies (14.2)], 4 patients were positive for neutralizing antibodies at baseline, and 2 (0.4%) additional patients (with unknown antibody status at baseline) were positive after treatment. Both patients had not received a botulinum toxin treatment in the 12 months prior to enrollment in the studies. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Upper Limb Spasticity in Pediatric Patients

Of the 907 patients treated with XEOMIN in clinical trials for treatment of pediatric spasticity [see Clinical Studies (14.2)], 7 patients were positive for neutralizing antibodies at baseline, and 4 (0.4%) additional patients (with unknown antibody status at baseline) were positive after treatment. All of these patients were treated with onabotulinumtoxinA and/or abobotulinumtoxinA prior to enrollment in the study. Patients who had never received a botulinum toxin treatment did not develop neutralizing antibodies after being treated with XEOMIN. Antibody measurements were not performed in patients with <21 kg body weight.  No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

Safety and effectiveness of XEOMIN in patients less than 18 years of age have not been established for lower limb spasticity, sialorrhea, cervical dystonia, blepharospasm, or glabellar frown lines [see Warnings and Precautions (5.1)].

Upper Limb Spasticity in Pediatric Patients, Excluding Spasticity Caused by Cerebral Palsy

Safety and effectiveness have been established in pediatric patients 2 to 17 years of age [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Clinical Studies (14.2)]. The safety and effectiveness of XEOMIN have been established by evidence from adequate and well-controlled studies of XEOMIN in patients 2 to 17 years of age with upper limb spasticity. A pediatric assessment for XEOMIN demonstrates that XEOMIN is safe and effective in another pediatric population. However, XEOMIN is not approved for such patient population due to marketing exclusivity for another botulinum toxin. Safety and effectiveness in pediatric patients below the age of 2 years have not been established [see Warnings and Precautions (5.1)].

Juvenile Animal Toxicity Data

In a study in which juvenile rats received intramuscular injections of Xeomin (0, 5, 10, or 30 Units/kg) every other week from postnatal day 21 for 10 weeks, decreased limb use, decreased body weight gain, skeletal muscle atrophy, and decreased bone growth and density were observed at all doses. Delayed female sexual maturation and male reproductive organ histopathology (atrophy of the germinal epithelium of the testis, associated with hypospermia) were observed at the mid and high doses, and mating behavior was impaired at the high dose. A no-effect dose for adverse effects on development in juvenile animals was not established. The lowest dose tested (5 Units/kg) is less than the human dose of 400 Units on a body weight (kg) basis.

8.5 Geriatric Use

Additions and/or revisions underlined:

Upper Limb Spasticity

Of the total number of 283 patients in the placebo-controlled studies in upper limb spasticity in adult patients [see Clinical Studies (14.2)], 118 were 65 years of age and over (70 treated with XEOMIN and 48 received placebo), which included 12 patients 75 years of age and over (7 treated with XEOMIN and 5 received placebo). No overall differences in safety or effectiveness were observed between older and younger adult patients. Other clinical studies have not identified differences in responses between older and younger adult patients, but increased sensitivity in older patients cannot be ruled out.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is XEOMIN?

XEOMIN is a prescription medicine:

• that is injected into muscles and used to:

  • treat increased muscle stiffness in the arm because of upper limb spasticity in adults.

  • treat increased muscle stiffness in the arm in children 2 to 17 years of age with upper limb spasticity, excluding spasticity caused by cerebral palsy.

• treat the abnormal head position and neck pain with cervical dystonia (CD) in adults.

• treat abnormal spasm of the eyelids (blepharospasm) in adults.

• improve the look of moderate to severe frown lines between the eyebrows (glabellar lines) for a short period of time (temporary) in adults.

It is not known if XEOMIN is safe and effective in children younger than:

• 2 years of age for the treatment of upper limb spasticity

• 18 years of age for the treatment of sialorrhea, cervical dystonia, blepharospasm, or glabellar lines

What are the possible side effects of XEOMIN?

XEOMIN may cause serious side effects, including:

See "What is the most important information I should know about XEOMIN?"

The most common side effects of XEOMIN in adults with chronic sialorrhea include:

The most common side effects of XEOMIN in adults with upper limb spasticity include:

The most common side effects of XEOMIN in children 2 to 17 years of age with upper limb spasticity include:

• nasal congestion, sore throat, and runny nose

• bronchitis

The most common side effects of XEOMIN in adults with cervical dystonia include:

The most common side effects of XEOMIN in adults with blepharospasm include:

The most common side effect of XEOMIN in adults with glabellar lines include:

05/10/2019 (SUPPL-74)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

Known hypersensitivity to any botulinum toxin product or to any of the components in the formulation.

5 Warnings and Precautions

5.3 Hypersensitivity Reactions

(Newly Added Subsection) 

Serious hypersensitivity reactions have been reported with botulinum toxin products. Hypersensitivity reactions include anaphylaxis, serum sickness, urticaria, soft tissue edema, and dyspnea. If serious and/or immediate hypersensitivity reactions occur, discontinue further injection of XEOMIN and institute appropriate medical therapy immediately.  The use of XEOMIN in patients with a known hypersensitivity to any botulinum neurotoxin or to any of the excipients (human albumin, sucrose), could lead to a life-threatening allergic reaction.

 

5.5 Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated for Blepharospasm

(Additions and/or revisions are underlined)

Reduced blinking from injection of botulinum toxin products in the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. As patients with previous eye surgery may have reduced corneal sensation, carefully assess corneal sensation before treatment. Vigorous treatment of any corneal epithelial defect should be employed.  This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.  Because of its anticholinergic effects, XEOMIN should be used with caution in patients at risk of developing narrow angle glaucoma.  To decrease the risk for ectropion, XEOMIN should not be injected into the medial lower eyelid area.

5.7 Human Albumin and Transmission of Viral Diseases

(Additions and/or revisions are underlined)

This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. and variant Creutzfeldt-Jakob disease (vCJD).  There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote.  No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following adverse reactions to XEOMIN are discussed in greater detail in other sections of the labeling:

• Hypersensitivity Reactions

   

6.1 Clinical Trials Experience

(Additions and/or revisions are underlined)

Upper Limb Spasticity

Table 5 lists the adverse reactions that occurred in greater than or equal to 2% of XEOMIN-treated patients in two placebo-controlled, Phase 3 studies in patients with upper limb spasticity. Study 1 and Study 2 were both double-blind, placebo-controlled studies, with an open-label extension. In the controlled portion of these studies, 283 patients received than or equal to 120 Units to 400 Units, of which 217 patients received at least 400 units of XEOMIN, and 182 patients received placebo. XEOMIN- treated patients were 20-79 years old (mean 56 years),and were predominantly male (58%) and white (84%).

Cervical Dystonia

The data described below reflect exposure to a single intramuscular dose of XEOMIN in a placebo-controlled, Phase 3 trial in patients with cervical dystonia. In this study, 159 patients received XEOMIN (78 were randomized to receive a total dose of 120 Units, and 81 were randomized to receive a total dose of 240 Units). XEOMIN-treated patients were 18 to 79 years old (mean 53 years), and were predominantly female (66%) and Caucasian (91%).  At study baseline, approximately  25% had mild, 50% had moderate, and 25% had severe cervical dystonia. Approximately 61% of XEOMIN-treated patients had previously received another botulinum toxin type A product. Table 6 lists adverse reactions that occurred in greater than or equal to 5% of XEOMIN-treated patients (in any treatment group) and greater than placebo.

Table 6: Adverse Reactions (greater than or equal to 5% ) and Greater for XEOMIN  than Placebo: Double-Blind Phase of the Placebo-Controlled Cervical Dystonia Study

Blepharospasm

Study 1 was a randomized, double-blind, placebo-controlled study that only included treatment-naïve patients. In the controlled portion, 22 patients received XEOMIN 25 Units, 19 patients received 50 Units, and 20 patients received placebo. XEOMIN-treated patients were 23 to 78 years of age (mean 55 years). Fifty-nine percent of the patients were women, 77% were Asian, and 23% White. No patients withdrew prematurely because of an adverse event. Table 7 lists the adverse reactions that occurred in greater than or equal to 6% of XEOMIN-treated patients and greater than placebo.

Table 7: Adverse Reactions (greater than or equal to 6%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled  Blepharospasm Study

 Study 2 was double-blind, place-controlled, flexible dose study with an open-label extension (OLEX) period. The study only included patients previously treated with onabotulinumtoxinA (Botox). In the controlled portion, 74 patients received XEOMIN at a mean dose of approximately 33 Units per eye (minimum 10 Units, maximum 50 Units). XEOMIN-treated patients were 22 to 79 years of age (mean 62 years), predominately female (65%), and Caucasian (60%). Table 8 lists the adverse reactions that occurred in greater than or equal to 5% of XEOMIN-treated patients and greater than placebo.

Table 8: Adverse Reactions (greater than or equal to 5% ) and Greater for XEOMIN  than Placebo: Double-Blind Phase of the Placebo-Controlled  Blepharospasm Study 2

6.2 Immunogenicity

(Additions and/or revisions are underlined)

As with all therapeutic proteins, there is a potential for immunogenicity.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other botulinumtoxinA products may be misleading.

Of the 1490 patients treated with XEOMIN in placebo-controlled clinical trials supporting approved indications , 5 (0.3%) patients were positive for neutralizing antibodies after treatment whose antibody status at baseline was unknown and 4 (0.2%) additional patients developed neutralizing antibodies after treatment. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Chronic Sialorrhea

Of the 180 patients treated with XEOMIN in the main phase and extension period of the chronic sialorrhea clinical trial, 1 (0.6%) patient was positive for neutralizing antibodies after treatment.  The patient had an antibody status unknown at baseline, and had not received a botulinum toxin treatment in the 12 months prior to enrollment in the study. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Upper Limb Spasticity

Of the 456 patients treated with XEOMIN in the main phase and open-label extension period of the upper limb spasticity clinical trials (Study 1 and Study 2), 4 patients were positive for neutralizing antibodies at baseline, and 2 (0.4%) additional patients (with unknown antibody status at baseline) were positive after treatment.  Both patients had not received a botulinum toxin treatment in the 12 months prior to enrollme nt in the studies. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Cervical Dystonia

Of the 227 patients treated with XEOMIN in the main phase and open-label extension period of the cervical dystonia clinical trial, 5 patients were positive for neutralizing antibodies at baseline, 1 (0.4%) patient (with unknown antibody status at baseline) was positive after treatment, and 4 (1.8%) additional patients developed neutralizing antibodies after treatment.  All of these patients were pre-treated with onabotulinumtoxinA prior to enrollment in the study. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Blepharospasm

Of the 163 patients treated with XEOMIN in the main phase and open-label extension period of the blepharospasm clinical trials (Study 1 and Study 2), 1 (0.6%) patient (with unknown antibody status at baseline) was positive for neutralizing antibodies after treatment. The patient had not received a botulinum toxin treatment in the 12 months prior to enrollment in the studies. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

Glabellar Frown Lines

Of the 464 patients treated with XEOMIN in the main phase and open-label extension period of the glabellar frown lines clinical trials (GL-1  and GL-2), no patients developed neutralizing antibodies after treatment. No patients demonstrated a secondary lack of treatment response due to neutralizing antibodies.

7 Drug Interactions

(Subsection title added; Additions and/or revisions are underlined)

7.1 Aminoglycosides and Other Agents Interfering with Neuromuscular Transmission

Co-administration of XEOMIN and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., tubocurarine-type muscle relaxants) should only be performed with caution as these agents may potentiate the effect of the toxin.

7.2 Anticholinergic Drugs

Use of anticholinergic drugs after administration of XEOMIN may potentiate systemic anticholinergic effects.

7.3 Other Botulinum Neurotoxin Products

The effect of administering different botulinum toxin products 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.

7.4 Muscle Relaxants

Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of XEOMIN.

8 Use in Specific Populations

8.5 Geriatric Use

(Additions and/or revisions are underlined)

Chronic Sialorrhea

Of the total number of 184 patients in the placebo-controlled study in chronic sialorrhea, 107 were 65 years of age and over (46 treated with XEOMIN 100 Units., 44 treated with XEOMIN 75 Units, and 17 received placebo). No differences in safety or effectiveness were observed between older and younger patients. Other clinical studies have not identified differences in responses between older and younger patients, but increased sensitivity in older patients cannot be ruled out.

Upper Limb Spasticity

Of the total number of 283 patients in the placebo-controlled studies in upper limb spasticity, 118 were 65 years of age and over,  (70 treated with XEOMIN and 7  48 received placebo), which included 12 patients 75 years of age and over. (7 treated with XEOMIN and 5 received placebo). No overall differences in safety or effectiveness were observed between older and younger patients. Other clinical studies have not identified differences in responses between older and younger patients, but increased sensitivity in older patients cannot be ruled out.

Cervical Dystonia

Of the total number of 233 patients in the placebo-controlled study in cervical dystonia , 29 were 65 years of age and over (19 treated with XEOMIN and 10 received placebo). Of these, ten XEOMIN-treated patients and four placebo-treated patients experienced an adverse event. For patients 65 years of age and over treated with XEOMIN, the most common adverse events were dysphagia (21%) and asthenia (11%).

Blepharospasm

Of the total number of 169 patients in the placebo-controlled studies in blepharospasm, 61 were 65 years of age and over (45 treated with XEOMIN and 16 received placebo). No overall difference in effectiveness was observed between older and younger patients.

Glabellar Lines

There are limited clinical data with XEOMIN in subjects 65 years of age and over in clinical studies with glabellar lines. Of the total number of 547 subjects in the placebo-controlled clinical studies, 21 subjects were 65 years of age and over. Efficacy was observed in 20% (3/15) of XEOMIN subjects 65 years of age and over. For the entire safety database of geriatric subjects, there was no increase in the incidence of adverse events related to treatment with XEOMIN.

 

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Swallowing, Speaking, or Breathing Difficulties or Other Unusual Symptoms

Advise patients to inform their healthcare provider if they develop any unusual symptoms, including difficulty with swallowing, speaking, or breathing, or if any existing symptom worsens. Inform patients of the risk of aspiration.

Ability to Operate Machinery or Vehicles

Counsel patients that if loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities.

Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated for Blepharospasm

Inform patients that injections of XEOMIN may cause reduced blinking or effectiveness of blinking, and that they should seek immediate medical attention if eye pain or irritation occurs following treatment.

 

07/03/2018 (SUPPL-73)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions are underlined)

Chronic Sialorrhea

Table 4 lists the adverse reactions that occurred in greater than or equal to 3% of XEOMIN-treated patients in the double-blind, placebo-controlled phase of the study in patients with chronic sialorrhea. The most common adverse reactions (greater than or equal to 4%) were tooth extraction, dry mouth, diarrhea, and hypertension. In the controlled portion of this study, 74 patients received 100 Units of XEOMIN and 36 patients received placebo. XEOMIN-treated patients were 21-80 years old (mean 65 years), and were predominantly male (71%) and white (99.5%).

Table 4: Adverse Reactions (greater than or equal to 3%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Chronic Sialorrhea Study

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

There are no adequate data on the developmental risk associated with the use of XEOMIN in pregnant women . XEOMIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. XEOMIN was embryotoxic in rats and increased abortions in rabbits when given at doses higher than the maximum recommended human dose (MRHD) for cervical dystonia (120 Units)), on a body weight basis.

In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

There are no data on the presence of XEOMIN in human milk, the effects on the breastfed infant, or the effects on milk produc tion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XEOMIN and any potential adverse effects on the breastfed infant from XEOMIN or from the underlying maternal conditions.

8.5 Geriatric Use Chronic Sialorrhea

(Additions and/or revisions are underlined)

Of the 184 patients in the placebo-controlled study in chronic sialorrhea, 107 (58%) were 65 years of age and over, including 17 of the 36 patients (47%) who received placebo, and 46 of the 74 patients (62%) treated with XEOMIN 100 Units. No differences in safety or effectiveness were observed between older and younger patients. Other clinical studies have not identified differences in responses between older and younger patients, but increased sensitivity in older patients cannot be ruled out.