AbobotulinumtoxinA

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

The botulinum toxin contained in Dysport can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulinum toxin injections, even for cosmetic purposes.

Call your doctor at once if you have any of these side effects, some of which can occur up to several weeks after an injection:

• trouble breathing, talking, or swallowing;
• hoarse voice, drooping eyelids;
• problems with vision;
• unusual or severe muscle weakness (especially in a body area that was not injected with the medication);
• loss of bladder control;
• crusting or drainage from your eyes;
• severe skin rash or itching;
• fast, slow, or uneven heartbeats; or
• chest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling.

Common side effects may include:

• muscle weakness near where the medicine was injected;
• bruising, bleeding, pain, redness, or swelling where the injection was given;
• headache, muscle pain or stiffness, neck pain;
• fever, cough, sore throat, runny or stuffy nose;
• drooping eyelids, dry or puffy eyes;
• nausea, dry mouth;
• trouble swallowing; or
• tired feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may not appear right away, but can include muscle weakness, trouble swallowing, and weak or shallow breathing.

Since botulinum toxin has a temporary effect and is given at widely spaced intervals, missing a dose is not likely to be harmful.

Since botulinum toxin has a temporary effect and is given at widely spaced intervals, missing a dose is not likely to be harmful.

Neurotoxin produced by Clostridium botulinum; disrupts neurotransmission by inhibiting release of acetylcholine from peripheral cholinergic and ganglionic autonomic nerve terminals.384 388 392 396

• If you need to store abobotulinumtoxinA at home, talk with your doctor, nurse, or pharmacist about how to store it.

• Botulinum Toxin Type A

There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely as abobotulinumtoxin A is not expected to be present in peripheral blood at recommended doses following intramuscular (IM) injection.

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions may occur rarely; immediate treatment (including epinephrine 1 mg/mL) should be available.

• Antibody formation: Higher doses or more frequent administration may result in neutralizing antibody formation and loss of efficacy.

• Cardiovascular events: Rarely, arrhythmia and myocardial infarction have been reported with use of onabotulinumtoxinA (another botulinum toxin formulation), sometimes in patients with preexisting cardiovascular disease.

• Dysphagia: Common when used for cervical dystonia and may persist for several weeks after administration. In severe cases, patients may require alternative feeding methods (eg, feeding tube). Risk factors include smaller neck muscle mass, bilateral injections into the sternocleidomastoid muscle, or injections into the levator scapulae. Risk of aspiration resulting from severe dysphagia is increased in patients when swallowing is already compromised. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.

• Systemic toxicity: [US Boxed Warning]: Distant spread of botulinum toxin beyond the site of injection has been reported; dysphagia and breathing difficulties have occurred and may be life threatening; other symptoms reported include asthenia, blurred vision, diplopia, dysarthria, dysphonia, generalized muscle weakness, ptosis, and urinary incontinence which may develop within hours or weeks following injection. Risk likely greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions. Systemic effects have occurred following use in approved and unapproved uses including lower than the maximum recommended total dose. Immediate medical attention required if respiratory, speech, or swallowing difficulties appear.

Disease-related concerns:

• Neuromuscular disease: Use with caution in patients with neuromuscular diseases (eg, myasthenia gravis, Eaton-Lambert syndrome) and neuropathic disorders (eg, amyotrophic lateral sclerosis).

• Ocular diseases: Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration when treating blepharospasm. Retrobulbar hemorrhages may occur from needle penetration into orbit when treating strabismus; spatial disorientation, double vision, or past-pointing may occur if one or more extraocular muscles are paralyzed. Covering the affected eye may help. Careful testing of corneal sensation, avoidance of lower lid injections, and treatment of epithelial defects are necessary. Use caution in patients with angle closure glaucoma.

• Respiratory disease: Use extreme caution in patients with preexisting respiratory disease; treatment of cervical dystonia using botulinum toxin may weaken accessory muscles that are necessary for these patients to maintain adequate ventilation. Serious breathing difficulties, including respiratory failure, have been reported. Risk of aspiration resulting from severe dysphagia is increased in patients with decreased respiratory function.

Dosage form specific issues:

• Albumin: Product contains albumin and may carry a remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease.

• Lactose: Product may contain lactose; do not administer to patients allergic to cow's milk protein.

• Product interchangeability: Botulinum products (abobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) are not interchangeable; potency units are specific to each preparation and cannot be compared or converted to any other botulinum product.

Special populations:

• Elderly: Temporary reduction in glabellar lines: Efficacy was not observed in older adults (≥65 years of age) and an increased frequency of ocular adverse events was reported in older adults compared to younger adults.

• Pediatric: Lower limb spasticity: Safety and effectiveness of injection into proximal muscles of the lower limb have not been established.

Other warnings/precautions:

• Chronic therapy: Long-term effects of chronic therapy unknown.

• Injection site: Use with caution if there is inflammation or excessive weakness or atrophy at the proposed injection site(s); use is contraindicated if infection is present.

• Hyperhidrosis: Safety in the treatment of hyperhidrosis has not been established. The possibility of an immune reaction resulting from an intradermal injection is unknown.

• Temporary reduction in glabellar lines: Appropriate use: Do not use more frequently than every 3 months. Patients with marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or the inability to substantially lessen glabellar lines by physically spreading them apart were excluded from clinical trials. Use with caution in patients with surgical alterations to the facial anatomy. Reduced blinking from injection of the orbicularis muscle can lead to corneal exposure and ulceration. Spatial disorientation, double vision, or past pointing may occur if one or more extraocular muscles are paralyzed.

IM Preparation

Only use sterile preservative-free 0.9% NaCl injection for reconstituting vials

Swirl gently to dissolve

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration

Reconstituted solution should be a clear, colorless, and free of particulate matter, otherwise it should not be injected

Cervical dystonia

• 500 units/vial: Reconstitute with 1 mL 0.9% NaCl (yields 50 units/0.1 mL)
• 300 units/vial: Reconstitute with 0.6 mL 0.9% NaCl (yields 50 units/0.1 mL)

Glabellar lines

• 300 units/vial: Reconstitute with 2.5 mL 0.9% NaCl (yields 10 units/0.08 mL [12 units/0.1 mL]) OR,
• Reconstitute 300 units/vial with 1.5 mL 0.0% NaCl (yields 10 units/0.05 mL [20 units/0.1 mL])

Upper limb spasticity

• Recommended concentration for ULS is 100-200 units/1 mL
• For adult administration only
• Steps for use of 5 mL of diluent for 500 unit vial
  • 1. 500 unit vial: Reconstitute with 2.5 mL 0.9% NaCl, gently mix and set the vial aside
  • 2. Withdraw 2.5 mL 0.9% NaCl into a 5 mL syringe
  • 3. Take the 5 mL syringe with the saline and draw up the reconstituted solution in the vial without inverting and gently mix the syringe (resulting concentration is 10 units/0.1 mL [100 units/1 mL])
  • 4. Use immediately after reconstitution in the syringe

Lower limb spasticity (LLS)

• For pediatric administration only
• Recommended concentration for LLS is 100-200 units/1 mL
• Vial reconstitution
  • 500-unit vial: Reconstitute with 2.5 mL 0.9% NaCl
  • 300-unit vial: Reconstitute with 1.5 mL 0.9% NaCl
  • Resulting concentrations are 20 units/0.1 mL; reconstituted solution should be clear, colorless, and without particulate matter
  • Further dilution with 0.9% NaCl may be required to achieve the final volume for injection

Storage

Store unreconstituted vials in refrigerator at 2-8°C (36-46°F)

Use each vial for only 1 injection session and for only 1 patient

Once reconstituted, store in the original container, refrigerated at 2-8°C (36-46°F) for up to 24 hr (must discard if not used within 24 hr)

Protected from light

Do not freeze reconstituted solution

Data not available

Animal studies have revealed evidence of maternal toxicity, abortions, and/or fetal malformations at high doses. There are no controlled data in human pregnancy. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Benefit should outweigh risk. US FDA pregnancy category: C