Incobotulinumtoxina

FDA Drug Information • Also known as: Xeomin

Brand Names: Xeomin
Drug Class: Acetylcholine Release Inhibitor [EPC], Neuromuscular Blocker [EPC]
Route: INTRAMUSCULAR
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: DISTANT SPREAD OF TOXIN EFFECT Postmarketing reports indicate that the effects of XEOMIN and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including lower limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and at lower doses [see Warnings and Precautions (5.1) ] . WARNING: DISTANT SPREAD OF TOXIN EFFECT See full prescribing information for complete boxed warning. The effects of XEOMIN and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults, particularly in those patients who have underlying conditions that would predispose them to these symptoms. ( 5.1 )

Description

11 DESCRIPTION The active ingredient of XEOMIN is botulinum toxin type A produced from fermentation of Hall strain Clostridium botulinum serotype A. The botulinum toxin complex is purified from the culture supernatant and then the active ingredient is separated from the proteins (hemagglutinins and non-hemagglutinins) through a series of steps yielding the active neurotoxin with molecular weight of 150 kDa, without accessory proteins. XEOMIN is a sterile white to off-white lyophilized powder intended for intramuscular or intra-salivary gland injection after reconstitution with preservative-free 0.9% Sodium Chloride Injection, USP [see Dosage Forms and Strengths (3) ] . One vial of XEOMIN contains 50 Units, 100 Units, or 200 Units of incobotulinumtoxinA, human albumin (1 mg), and sucrose (4.7 mg). The primary release procedure for XEOMIN uses a cell-based potency assay to determine the potency relative to a reference standard. One Unit corresponds to the median intraperitoneal lethal dose (LD 50 ) in mice. As the method for conducting the assay is specific to XEOMIN, Units of biological activity of XEOMIN cannot be converted into Units of any other botulinum toxin assessed with other specific assays.

What Is Incobotulinumtoxina Used For?

1 INDICATIONS AND USAGE XEOMIN is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for the treatment or improvement of: Chronic sialorrhea in patients 2 years of age and older ( 1.1 ) Upper limb spasticity in adults ( 1.2 ) Upper limb spasticity in pediatric patients 2 to 17 years of age, excluding spasticity caused by cerebral palsy ( 1.2 ) Cervical dystonia in adults ( 1.3 ) Blepharospasm in adults ( 1.4 ) the appearance of upper facial lines in adults: moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity ( 1.5 ) moderate to severe horizontal forehead lines associated with frontalis muscle activity ( 1.5 ) moderate to severe lateral canthal lines associated with orbicularis oculi muscle activity ( 1.5 ) 1.1 Chronic Sialorrhea XEOMIN is indicated for the treatment of chronic sialorrhea in patients 2 years of age and older. 1.2 Upper Limb Spasticity Upper Limb Spasticity in Adult Patients XEOMIN is indicated for the treatment of upper limb spasticity in adult patients. Upper Limb Spasticity in Pediatric Patients, Excluding Spasticity Caused by Cerebral Palsy XEOMIN is indicated for the treatment of upper limb spasticity in pediatric patients 2 to 17 years of age, excluding spasticity caused by cerebral palsy. 1.3 Cervical Dystonia XEOMIN is indicated for the treatment of cervical dystonia in adult patients. 1.4 Blepharospasm XEOMIN is indicated for the treatment of blepharospasm in adult patients. 1.5 Upper Facial Lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines) XEOMIN is indicated in adult patients for the temporary improvement in the appearance of upper facial lines: moderate to severe glabellar lines (GL) associated with corrugator and/or procerus muscle activity moderate to severe horizontal forehead lines (HFL) associated with frontalis muscle activity moderate to severe lateral canthal lines (LCL) associated with orbicularis oculi muscle activity.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Chronic Sialorrhea : Chronic Sialorrhea in Adults: the recommended total dose is 100 Units per treatment session consisting of 30 Units per parotid gland and 20 Units per submandibular gland, no sooner than every 16 weeks ( 2.2 ) Chronic Sialorrhea in Pediatric Patients: the recommended dose is based on body weight administered in a 3:2 dose ratio into the parotid and submandibular glands, respectively, no sooner than every 16 weeks; ultrasound guidance recommended ( 2.2 ) Upper limb spasticity, cervical dystonia, and blepharospasm: the optimum dose, frequency, and number of injection sites in the treated muscle(s) should be based on severity and prior treatment response in patients previously treated with botulinum toxin; individualize dosing for each patient: Upper Limb Spasticity in Adults: the recommended total dose is up to 400 Units, divided among affected muscles ( 2.3 ) Upper Limb Spasticity in Pediatric Patients, excluding spasticity caused by cerebral palsy: the recommended total dose is 8 Units/kg (maximum 200 Units) per single upper limb or 16 Units/kg (maximum 400 U) in both upper limbs, divided among affected muscles ( 2.3 ) Cervical Dystonia: the recommended initial dose is 120 Units per treatment session ( 2.4 ) Blepharospasm: the recommended initial dose is 50 Units (25 Units per eye) ( 2.5 ) Upper Facial Lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines): When treating all three areas simultaneously (glabellar lines, horizontal forehead lines, and lateral canthal lines), the maximum recommended dose is 64 Units ( 2.6 ). When not treating simultaneously: Glabellar Lines: four Units into each of five sites, for a maximum dose of 20 Units Horizontal Forehead Lines treated simultaneously with Glabellar Lines: for HFL four Units into each of five sites (20 Units) and four Units into each of five GL sites (20 Units), for a maximum dose of 40 Units Lateral Canthal Lines: four Units into each of three sites per side (six injection sites in total), for a maximum dose of 12 Units per side (24 Units in total) Administer retreatment with XEOMIN no more frequently than every three months. Reconstituted XEOMIN: Is intended for intramuscular or intraglandular injection in the parotid and submandibular glands only ( 2.7 ) Use for only one injection session and for only one patient ( 2.7 ) Instructions are specific for 50 Unit, 100 Unit, and 200 Unit vials ( 2.7 ) Store in a refrigerator (2°C to 8°C) and use within 24 hours ( 2.7 ) 2.1 Instructions for Safe Use The potency Units of XEOMIN for injection 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 Warnings and Precautions (5.2) and Description (11) ] . Reconstituted XEOMIN is intended for intramuscular or intra-salivary gland injection only. Do not exceed...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions to XEOMIN are discussed in greater detail in other sections of the labeling: Spread of Effects from Toxin [see Warnings and Precautions (5.1) ] Lack of Unit Equivalency between Botulinum Toxin Products [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Dysphagia and Breathing Difficulties [see Warnings and Precautions (5.4) ] Corneal Exposure, Corneal Ulceration, and Ectropion in Patients Treated with XEOMIN for Blepharospasm [see Warnings and Precautions (5.5) ] Risk of Ptosis in Patients Treated for Glabellar Lines [see Warnings and Precautions (5.6) ] Human Albumin and Transmission of Viral Diseases [see Warnings and Precautions (5.7) ] The most commonly observed adverse reactions at rates specified below and greater than placebo are: Chronic Sialorrhea: Chronic Sialorrhea in Adults (≥4% of patients) : tooth extraction, dry mouth, diarrhea, and hypertension ( 6.1 ) Chronic Sialorrhea in Pediatric Patients (≥1% of patients): bronchitis, headache, and nausea/vomiting ( 6.1 ) Spasticity: Upper Limb Spasticity in Adults (≥2% of patients) : seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection ( 6.1 ) Upper Limb Spasticity in Pediatric Patients (≥3% of patients) : nasopharyngitis and bronchitis ( 6.1 ) Cervical Dystonia (≥5% of patients) : dysphagia, neck pain, muscle weakness, injection site pain, and musculoskeletal pain ( 6.1 ) Blepharospasm (≥10% of patients) : eyelid ptosis, dry eye, visual impairment, and dry mouth ( 6.1 ) Upper facial lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines): (>1% of patients) : injection site bruising ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merz Pharmaceuticals, LLC at 888-493-6646 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Chronic Sialorrhea Chronic Sialorrhea in Adult Patients Table 6 lists the adverse reactions that occurred in ≥3% of XEOMIN-treated patients in the double-blind, placebo-controlled phase of the study in adult patients with chronic sialorrhea [see Clinical Studies (14.1) ] . The most common adverse reactions (≥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 6: Adverse Reactions (≥3%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Adult Chronic Sialorrhea Study Adverse Reaction XEOMIN 100 Units (N = 74) % Placebo (N = 36) % Tooth extraction 5 0 Dry mouth 4 0 Diarrhea 4 3 Hypertension 4 3 Fall 3 0 Bronchitis 3 0 Dysphonia 3 0 Back pain 3 0 Dry eye 3 0 Chronic Sialorrhea in Pediatric Patients Table 7 lists the adverse reactions that occurred in ≥1% of XEOMIN-treated patients 6-17 years of age in the double-blind, placebo-controlled portion of the study in pediatric patients with chronic sialorrhea [see Clinical Studies (14.1) ] . Of the patients 6-17 years of age, 148 patients received a dose of XEOMIN according to body weight, and 72 patients received placebo. Thirty-five patients 2-5 years of age received an open-label dose of XEOMIN according to body weight. XEOMIN-treated patients were 2-17 years of age (mean 10 years), predominately male (63%) and White (100%). Table 7: Adverse Reactions (≥1%) and Greater for XEOMIN than Placebo: Double-Blind Phase of the Placebo-Controlled Pediatric Chronic Sialorrhea Study Adverse Reaction XEOMIN (6-17 years) (N = 148) % Placebo (6-17 years) (N = 72) % Bronchitis 1 0 Headache 1 0...

Drug Interactions

7 DRUG INTERACTIONS Aminoglycosides or other agents that interfere with neuromuscular transmission may potentiate the effect of XEOMIN; co-administer only with caution and close observation ( 7 ) 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.

Contraindications

4 CONTRAINDICATIONS XEOMIN is contraindicated in patients with: Known hypersensitivity to any botulinum toxin product or to any of the components in the formulation [see Warnings and Precautions (5.3) and Description (11) ] . Infection at the proposed injection site(s) because it could lead to severe local or disseminated infection. Known hypersensitivity to the active substance botulinum neurotoxin type A or to any of the excipients ( 4 , 5.3 ) Infection at the proposed injection sites ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy 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. Data Animal Data When XEOMIN was administered intramuscularly to pregnant rats during organogenesis (3 Units/kg, 10 Units/kg, or 30 Units/kg on gestational days [GDs] 6, 12, and 19; or 7 Units/kg on GDs 6 to 19; or 2 Units/kg, 6 Units/kg, or 18 Units/kg on GDs 6, 9, 12, 16, and 19), decreases in fetal body weight and skeletal ossification were observed at doses that were also maternally toxic. The no-effect level for embryotoxicity in rats was 6 Units/kg (3 times the MRHD for cervical dystonia on a body weight basis). Intramuscular administration to pregnant rabbits during organogenesis (1.25 Units/kg, 2.5 Units/kg, or 5.0 Units/kg on GDs 6, 18, and 28) resulted in an increased rate of abortion at the highest dose, which was also maternally toxic. In rabbits, the no-effect level for increased abortion was 2.5 Units/kg (similar to the MRHD for cervical dystonia on a body weight basis).

Overdosage

10 OVERDOSAGE Excessive doses of XEOMIN may be expected to produce neuromuscular weakness with a variety of symptoms, particularly when treated intramuscularly. Respiratory support may be required where excessive doses cause paralysis of the respiratory muscles. In the event of overdose, the patient should be medically monitored for symptoms of excessive muscle weakness or muscle paralysis [see Warnings and Precautions (5.1 , 5.4) ]. Symptomatic treatment may be necessary. Symptoms of overdose are not likely to be present immediately following injection. Should accidental injection or oral ingestion occur, the person should be medically supervised for several weeks for signs and symptoms of excessive muscle weakness or paralysis. There is no significant information regarding overdose from clinical studies of XEOMIN. In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 770-488-7100. More information can be obtained at http://www.cdc.gov/ncidod/srp/drugs/formulary.html#1a .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied XEOMIN for injection is a sterile white to off-white lyophilized powder supplied in Type 1 borosilicate glass single-dose vials with tamper-proof aluminum seals and bromobutyl rubber closures that are not made with natural rubber latex in the following pack sizes: Upper Limb Spasticity and Cervical Dystonia Package XEOMIN 50 Units XEOMIN 100 Units XEOMIN 200 Units Carton with one single-dose vial NDC 0259-1605-01 NDC 0259-1610-01 NDC 0259-1620-01 Chronic Sialorrhea and Blepharospasm Package XEOMIN 50 Units XEOMIN 100 Units Carton with one single-dose vial NDC 0259-1605-01 NDC 0259-1610-01 Upper Facial Lines (Glabellar Lines, Horizontal Forehead Lines, and Lateral Canthal Lines) Package XEOMIN 50 Units XEOMIN 100 Units Carton with one single-dose vial NDC 46783-161-01 NDC 46783-160-01 Storage and Handling Store unopened vials of XEOMIN at or below 25°C (77°F). Refrigeration of unopened vials is not required. Do not use after the expiration date on the vial. Reconstituted XEOMIN may be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours until time of use [see Dosage and Administration (2.7) ].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.