AbobotulinumtoxinA

Name: AbobotulinumtoxinA

What is the most important information I should know about Dysport?

You should not receive this medicine if you are allergic to botulinum toxin or cow's milk, or if you have an infection, swelling, or muscle weakness in the area where the medicine will be injected.

The botulinum toxin contained in Dysport can spread to other body areas beyond where it was injected. This can cause serious life-threatening side effects.

Call your doctor at once if you have a hoarse voice, drooping eyelids, vision problems, severe muscle weakness, loss of bladder control, or trouble breathing, talking, or swallowing. Some of these effects can occur up to several weeks after a botulinum toxin injection.

How is Dysport given?

This medication is injected into a muscle. A doctor, nurse, or other healthcare provider will give you this injection. Botulinum toxin injections should be given only by a trained medical professional, even when used for cosmetic purposes.

Dysport injections should be spaced at least 3 months apart.

Your injection may be given into more than one area at a time, depending on the condition being treated.

The effects of a Dysport injection are temporary. Your symptoms may return completely within 3 months after an injection. After repeat injections, it may take less and less time before your symptoms return, especially if your body develops antibodies to the botulinum toxin.

Do not seek botulinum toxin injections from more than one medical professional at a time. If you switch healthcare providers, be sure to tell your new provider how long it has been since your last botulinum toxin injection.

Using this medicine more often than prescribed will not make it more effective and may result in serious side effects.

Advice to Patients

  • Importance of providing a copy of the FDA-approved medication guide and reviewing its contents with every patient.384 400 Instruct patients to read medication guide prior to initiation of therapy and each time prescription is refilled.384 400

  • Advise patients and/or caregivers to seek immediate medical attention if unexpected muscle weakness, swallowing, speech, or respiratory disorders occur, or if any existing symptoms worsen or persist.384 400

  • Advise patients that abobotulinumtoxinA can cause loss of strength, muscle weakness, blurred vision, or drooping eyelids, and that they should not drive a car, operate machinery, or engage in any other potentially hazardous activities during treatment.384 400

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., neuromuscular disorders).384 400

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.384 400

  • Importance of informing patients of other important precautionary information.384 400 (See Cautions.)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intramuscular:

Dysport: 300 units (1 ea); 500 units (1 ea) [contains albumin human, milk protein]

Dysport (Glabellar Lines): 300 units (1 ea [DSC]) [contains albumin human, milk protein]

Off Label Uses

Acquired nystagmus

Botulinum toxin type A has been found to be objectively and subjectively effective in treating acquired nystagmus and its consequent oscillopsia and impaired vision in a few small case series and case reports. Botulinum toxin type A may be useful in certain patients who have contraindications to other therapies, but it cannot be recommended for routine symptomatic treatment of acquired nystagmus until data from controlled studies enrolling larger numbers of patients can confirm its efficacy and long-term safety.

Anal fissures

Evidence-based guidelines recommend botulinum toxin A IM injection as an option for the treatment of anal fissures in adults who have not responded to preferred therapy. Healing rates do not appear to be affected by dose, formulation, or injection technique, although using an anterior injection location for posterior anal fissures may provide benefit over usual posterior administration. It is important to note that botulinum toxin A formulations are not interchangeable.

Hand dystonia

Botulinum toxin is safe and effective for the majority of patients with primary dystonia of the hand and has been recommended for consideration for this use by the European Federation of Neurological Societies/Movement Disorder Society-European Section Task Force. Other drug therapies are generally not effective and produce intolerable adverse effects. Larger controlled trials are needed to document optimal dosing, administration techniques, frequency of repeat treatments, and effects of long-term use. Treatment is rarely continued beyond 2 years.

Sialorrhea (drooling) (adults)

The use of botulinum toxin A for decreasing or controlling sialorrhea has demonstrated benefit in randomized controlled trials and meta-analyses in patients with various neurological conditions. EFNS guidelines on the clinical management of ALS recommend botulinum toxin A in patients refractory to first-line therapy. An AAN report classifies botulinum toxin A as probably safe and effective in Parkinson-related sialorrhea. Additional study is needed to determine the expected duration of response, potential candidates, optimal dosing regimens, and standardization of injection procedures.

Spasticity of cerebral palsy (children/adolescents)

Data in children are conflicting. The duration of response is typically 3 to 4 months, and some experts recommend dosing no more frequently than every 3 months. Because the different formulations of botulinum toxin type A are not bioequivalent, caution should be exercised in determining the appropriate dose. The potential for severe generalized weakness should also be considered.

Tardive dyskinesia

Evidence from small, noncontrolled trials suggests some benefit with botulinum toxin A for treatment of localized tardive dyskinesia (eg, orofacial, head and neck, cervical). Evaluation of data is limited because several studies do not specify what botulinum toxin type A product was used. Use of abobotulinumtoxinA has been evaluated primarily in small noncontrolled trials and case reports demonstrating benefit in most patients. AAN clinical practice guidelines find the data inadequate to support or refute the use of botulinum toxin type A for treatment of tardive dyskinesia.

Reconstitution

Reconstitute with sterile, preservative free 0.9% sodium chloride. No more than 2.5 mL of diluent should be introduced into the vial. Swirl gently to dissolve; do not shake. Preparation instructions vary by indication and strength; use appropriate reconstitution methods. Use immediately after reconstitution in the syringe.

Cervical dystonia: Reconstitute 300-unit vial with 0.6 mL of diluent to obtain a concentration of 500 units/mL (50 units per 0.1 mL); reconstitute 500-unit vial with 1 mL of diluent to obtain a concentration of 500 units/mL (50 units per 0.1 mL); alternatively, may reconstitute 500-unit vial with 2 mL of diluent to obtain a concentration of 250 units/mL (25 units per 0.1 mL).

Glabellar lines: Reconstitute 300-unit vial with 2.5 mL of diluent to obtain a concentration of 10 units per 0.08 mL (12 units per 0.1 mL); alternatively, may reconstitute 300-unit vial with 1.5 mL of diluent to obtain a concentration of 10 units per 0.05 mL (20 units per 0.1 mL).

Lower limb spasticity:

Adults: Reconstitute 300-unit vial with 1.5 mL of diluent or 500-unit vial with 2.5 mL of diluent to obtain a concentration of 200 units/mL; or reconstitute 300-unit vial with 3 mL of diluent to obtain a concentration of 100 units/mL Alternatively, the 500-unit vial can be further diluted to obtain a concentration of 100 units/mL. To do this, reconstitute the 500-unit vial with 5 mL of diluent. Using a 5 mL syringe, draw up an additional 2.5 mL of the diluent; then draw up 2.5 mL of the reconstituted solution. Do not invert; mix gently.

Pediatrics (2 years and older): Reconstitute 300-unit vial with 1.5 mL of diluent or 500-unit vial with 2.5 mL of diluent to obtain a concentration of 200 units/mL. Further dilution may be required to achieve the final volume for injection.

Upper limb spasticity: Reconstitute 300-unit vial with 1.5 mL of diluent to obtain a concentration of 200 units/mL; or reconstitute 300-unit vial with 3 mL diluent to obtain a concentration of 100 units/mL. Reconstitute the 500-unit vial with 2.5 mL of diluent to obtain a concentration of 200 units/mL. Alternatively, the 500-unit vial can be further diluted to obtain a concentration of 100 units/mL. To do this, reconstitute the 500-unit vial with 5 mL of diluent. Using a 5 mL syringe, draw up an additional 2.5 mL of the diluent; then draw up 2.5 mL of the reconstituted solution. Do not invert; mix gently.

Storage

Store undiluted vials under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. After reconstitution, store vials in original container under refrigeration, protect from light, and use within 24 hours (does not contain preservative); single-use vials. Do not freeze after reconstitution.

Adverse Reactions

Cervical dystonia: Frequency not always defined.

Cardiovascular: Decreased heart rate

Central nervous system: Voice disorder (≤28%), fatigue (12%), headache (11%), facial paresis (≤11%), dizziness (4%)

Endocrine & metabolic: Increased serum glucose

Gastrointestinal: Dysphagia (15% to 39%), xerostomia (13% to 39%)

Immunologic: Antibody development (binding or neutralizing; 3%)

Infection: Infection (13%)

Local: Discomfort at injection site (13% to 22%), pain at injection site (5%)

Neuromuscular & skeletal: Myasthenia (11% to 56%), musculoskeletal pain (7%), amyotrophy (1%)

Ophthalmic: Eye disease (≤17%; includes accommodation disorder, blurred vision, decreased visual acuity, diplopia, dryness, pain, pruritus)

Respiratory: Dyspnea (3%; onset: ~1 week; duration: ~3 weeks)

Glabellar lines: 1% to 10%:

Central nervous system: Headache (9%)

Dermatologic: Contact dermatitis (2% to 3%)

Gastrointestinal: Nausea (2%)

Genitourinary: Hematuria (2%)

Immunologic: Antibody development (<1%)

Infection: Influenza (2% to 3%)

Local: Pain at injection site (3%), discomfort at injection site (2% to 3%), injection site reaction (2% to 3%), swelling at injection site (2% to 3%)

Ophthalmic: Blepharoptosis (2%), eyelid edema (2%)

Respiratory: Nasopharyngitis (10%), upper respiratory tract infection (3%), bronchitis (2% to 3%), cough (2% to 3%), pharyngolaryngeal pain (2% to 3%), sinusitis (2%)

Upper limb spasticity: Frequency not always defined; as reported with doses of 500 units to 1,000 units.

Cardiovascular: Hypertension (1% to 2%), syncope (1% to 2%)

Central nervous system: Myasthenia (2% to 4%), dizziness (3%), falling (3%), depression (2% to 3%), convulsions (2%), fatigue (2%), headache (2%), hypoesthesia (2%), seizure (partial; ≤2%), abnormal gait (<1%), feeling of heaviness (<1%), hypertonia (<1%)

Endocrine & metabolic: Increased serum triglycerides (1% to 2%)

Gastrointestinal: Constipation (2%), nausea (2%), diarrhea (1% to 2%), dysphagia (<1%)

Genitourinary: Urinary tract infection (3%)

Hematologic & oncologic: Bruise (1% to 2%)

Immunologic Antibody development (7%; neutralizing: ≤4%)

Infection: Infection (2%), influenza (2%)

Local: Injection site reaction

Neuromuscular & skeletal: Musculoskeletal pain (3%), back pain (2%), limb pain (2%), weakness (1% to 2%)

Respiratory: Nasopharyngitis (4%), cough (2%)

Miscellaneous: Accidental injury (2%)

Lower limb spasticity: As reported in children and adolescents.

>10%:

Infection: Influenza (10% to 14%)

Respiratory: Upper respiratory tract infection (20%), nasopharyngitis (9% to 16%), cough (7% to 14%), pharyngitis (11%)

Miscellaneous: Fever (7% to 12%)

1% to 10%:

Central nervous system: Epilepsy (≤7%), seizure (≤7%), myasthenia (5%)

Gastrointestinal: Vomiting (6% to 8%), nausea (2% to 5%), viral gastroenteritis (2% to 4%)

Immunologic: Antibody development (4%; neutralizing: 2%)

Infection: Varicella (5%)

Neuromuscular & skeletal: Limb pain (7%)

Otic: Otic infection (4%)

Respiratory: Bronchitis (7% to 8%), rhinitis (5%), viral respiratory tract infection (2% to 5%), oropharyngeal pain (2% to 4%)

Any indication: Postmarketing and/or case reports (Limited to important or life-threatening): Burning sensation, connective tissue disease (excessive granulation tissue), erythema, photophobia, vertigo

Pharmacology

Mechanism of Action

Neurotoxin from Clostridium botulinum; prevents ACh release from presynaptic membrane

Pharmacokinetics

Onset of action: Cervical Dystonia: 2-4 weeks

Duration cervical dystonia: Up to 4 months

Liver Dose Adjustments

No adjustment recommended

Precautions

US BOXED WARNING:
Distant Spread of Toxin Effect:
-Postmarketing reports indicate that the effects of this drug 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 spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to or lower than the maximum recommended total dose.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age) for any indication.

Consult WARNINGS section for additional precautions.

AbobotulinumtoxinA Breastfeeding Warnings

Safety has not been established. Excreted into human milk: Unknown Excreted into animal milk: Data not available

No data exist on the medical use of this drug during breastfeeding. However, one infant was safely breastfed during maternal botulism and no botulinum toxin was detectable in the milk or infant. Since the doses used medically are far lower than those that cause botulism, amounts ingested by the infant, if any, are expected to be insignificant and not cause any adverse effects in breastfed infants. No special precautions are required.

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