Dosing & Uses
Dosage Forms & Strengths
injection, powder for reconstitution
- 300 units/vial
- 500 units/vial
Cervical Dystonia
Initial: 500 unit IM divided among affected muscles
Retreat every 12-16 weeks or longer: 250-1000 unit IM
Titrate in 250-unit steps
Spasticity
Indicated for treatment of spasticity in adults
Select dose based on muscles affected, severity of muscle activity, prior response to treatment, and adverse event history (EMG guidance recommended)
Do not inject >1 mL at any single injection site; the maximum total dose (upper and lower limb combined) is 1500 units
Repeat treatment when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection
A majority of patients are retreated between 12-16 weeks, although some may have a longer response (eg, 20 wk)
Upper limb spasticity
- Dose per muscle
- In the clinical trial, doses of 500-1000 units were divided among selected upper limb muscles at a given treatment session
- Flexor carpi radialis: 100-200 units in 1-2 sites
- Flexor carpi ulnaris: 100-200 units in 1-2 sites
- Flexor digitorum profundus: 100-200 units in 1-2 sites
- Flexor digitorum sublimis: 100-200 units in 1-2 sites
- Brachialis: 200-400 units in 1-2 sites
- Brachioradialis: 100-200 units in 1-2 sites
- Biceps brachii: 200-400 units divided in 1-2 sites
- Pronator Teres: 100-200 units in 1 site
Lower limb spasticity
- Dose per muscle
- In the clinical trial, doses of 1000-1500 units were divided among selected lower limb muscles at a given treatment session
- Gastrocnemius medial head: 100-150 units in 1 site
- Gastrocnemius lateral head: 100-150 units in 1 site
- Soleus: 330-500 units in 3 sites
- Tibialis posterior: 200-300 units in 2 sites
- Flexor digitorum longus: 130-200 units in 1-2 sites
- Flexor hallucis longus: 70-200 units in 1 site
Glabellar Lines
50 units total divided in 5 equal doses IM to affected muscles
Retreat no sooner than 3 months
Dosage Modifications
Renal or hepatic impairment: No dose adjustment necessary
Essential Blepharospasm (Orphan)
Orphan indication sponsor
- Porton International, Inc; 1155 15th Street, N.W., #315; Washington, DC 20005
Spasmodic Torticollis (Orphan)
Treatment of spasmodic torticollis (cervical dystonia)
Orphan indication sponsor
- Ipsen Biopharm Limited; 1 Bath Road Maidenhead, Berkshire, SL6 4UH; UK
Dosage Forms & Strengths
injection, powder for reconstitution
- 300 units/vial
- 500 units/vial
Lower Limb Spasticity
Indicated for lower limb spasticity in children aged ≥2 yr
<2 years: Safety and efficacy not established
≥2 years
- Select dose based on affected muscle, spasticity severity, and treatment history with botulinum toxins
- Total dose per treatment session: Not to exceed 10-15 units/kg for unilateral lower limb injections or 20-30 units/kg for bilateral lower limb injections or 1000 units, whichever is less
- Divide the total dose between the affected spastic muscles of the lower limb(s)
- When possible, the dose should be distributed across more than 1 injection site in any single muscle
- Not to exceed 0.5 mL in any single injection site
- Gastrocnemius (unilateral injection)
- 6-9 units/kg per muscle per leg
- Up to 4 injections per muscle
- Soleus (unilateral injection)
- 4-6 units/kg per muscle per leg
- Up to 2 injections per muscle
- Total dose
- 10-15 units/kg divided across both muscles (unilateral), OR
- 30 units/kg for bilateral injection, OR
- 100 units, whichever is lower
- Up to 6 injections per muscle (unilateral)
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Dysphagia (15%)
Dry mouth (13%)
Headache (11%)
Inj site discomfort (13%)
Muscle weakness (16%)
Fatigue (12%)
1-10%
Dyspnea (3%)
Facial paresis (5%)
Dysphonia (6%)
Injection site pain (5%)
Musculoskeletal pain (7%)
Eye disorders (7%)
Postmarketing Reports
Hypoesthesia
Warnings
Black Box Warnings
Effects of all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects
These symptoms 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 death have been reported
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 adults, 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
Contraindications
Hypersensitivity
Allergy to cow milk protein
Injection site infection
Cautions
Asthma, neuromuscular disorder, facial abnormalities, ptosis
Concomitant anticholinergic drugs, neuromuscular blockers or muscle relaxants
Toxin may spread - watch for dyspnea, dysphagia or speech impairment
Product contains albumin, a derivative of human blood; based on effective donor screening and product manufacturing processes; 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
Neutralizing antibody formation and loss of efficacy associated with higher doses or more frequent administration of the drug
Arrhythmia and myocardial infarction reported with use
Dysphagia reported with use for cervical dystonia; may persist for several weeks following administration and could cause the patient to require alternative feeding methods, including a feeding tube; smaller neck muscle mass, injections into the elevator scapulae or injections into the sternocleidomastoid muscle may increase risk of dysphagia; risk of aspiration may result from severe dysphagia when swallowing is already compromised; occurrence may be reduced by limiting the dose injected into sternocleidomastoid muscle
Use caution in patients with neuromuscular disease, including myasthenia gravis and Eaton-Lambert syndrome, and neuropathic disorders, such as, amyotrophic lateral sclerosis
Injection of the orbicularis muscle may reduce blinking and lead to corneal exposure and ulceration, when treating blepharospasm
Use caution when treating patients with preexisting respiratory disease; treatment of cervical dystonia, may weaken accessory muscles necessary to patients to maintain adequate ventilation; serious breathing difficulties, including respiratory failure reported
Pregnancy & Lactation
Pregnancy: There are no adequate and well-controlled clinical studies in pregnant women; only use during pregnancy if potential benefit justifies potential risk to fetus
Lactation: There are no data on the presence of drug in human or animal milk, the effects on the breastfed child, or effects on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from the drug or from the underlying maternal condition
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
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
Administration
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
Images
Patient Handout
Formulary
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