Dysport

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)

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Amyotrophic lateral sclerosis (Lou Gehrig's disease) or
• Dermatochalasis (a skin problem) or
• Lambert-Eaton syndrome (nerve-muscle disorder) or
• Motor neuropathy (muscle and nerve problem) or
• Myasthenia gravis (severe muscle weakness) or
• Sebaceous skin, thick (oily or fatty skin) or
• Surgery on the face, history of—May increase risk for more serious side effects.

• Breathing problems (eg, asthma, emphysema) or
• Dysphagia (trouble swallowing) or
• Ptosis (droopy eyelid)—Use with caution. May make these conditions worse.

• Cow's milk protein allergy, history of or
• Infection at the injection site—Should not be used in patients with these conditions.

WARNING: DISTANT SPREAD OF TOXIN EFFECT
The effects of Dysport 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 occur in adults, particularly in those patients who have underlying conditions that would predispose them to these symptoms.

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. Tell your doctor if you have ever had a side effect after receiving a botulinum toxin in the past

To make sure Dysport is safe for you, tell your doctor if you have:

• amyotrophic lateral sclerosis (ALS, or "Lou Gehrig's disease");

• myasthenia gravis;

• Lambert-Eaton syndrome;

• a breathing disorder such as asthma or emphysema;

• problems with swallowing;

• facial muscle weakness (droopy eyelids, weak forehead, trouble raising your eyebrows);

• a change in the normal appearance of your face;

• a seizure disorder;

• bleeding problems;

• heart disease;

• diabetes;

• if you have had or plan to have surgery (especially on your face); or

• if you have ever received other botulinum toxin injections such as Botox, Myobloc, or Xeomin (especially in the last 4 months).

Dysport is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether Dysport passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Dysport is generally not used in children. However, this medicine may be used to treat lower limb muscle stiffness in children as young as 2 years old.

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.

Dysport may impair your vision or depth perception. Be careful if you drive or do anything that requires you to be able to see clearly.

Avoid going back to your normal physical activities too quickly after receiving an injection.

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;

• pain or burning when you urinate, red or pink urine;

• 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;

• dizziness, depressed mood;

• bruising, bleeding, pain, redness, or swelling where the injection was given;

• headache, muscle pain, pain in your arms or legs;

• fever, cough, sore throat, runny or stuffy nose;

• drooping eyelids, dry or puffy eyes;

• nausea, dry mouth;

• trouble swallowing; or

• feeling tired.

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.

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

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

AbobotulinumtoxinA is used to treat the abnormal head position and neck pain that result from cervical dystonia (severe muscle spasms of the neck). This medicine is also used cosmetically to improve the appearance of deep facial lines or wrinkles between the eyebrows (glabellar lines). It is also used to treat upper and lower limb spasms.

AbobotulinumtoxinA is a botulinum toxin A product. It works on the nervous system to relax the muscles.

This medicine is available only with your doctor's prescription and will be administered by your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of abobotulinumtoxinA in children with cervical dystonia or upper limb spasms, and in children younger than 2 years of age with lower limb spasms. Safety and efficacy have not been established.

Use of abobotulinumtoxinA to treat glabellar lines is not recommended in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of abobotulinumtoxinA in the elderly. However, elderly patients are more sensitive to the effects of this medicine than younger adults and are more likely to have falls, weakness, or side effects related to the eyes, which may require caution in patients receiving abobotulinumtoxinA for lower limb spasticity and glabellar lines.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Amyotrophic lateral sclerosis (Lou Gehrig's disease) or
• Dermatochalasis (a skin problem) or
• Lambert-Eaton syndrome (nerve-muscle disorder) or
• Motor neuropathy (muscle and nerve problem) or
• Myasthenia gravis (severe muscle weakness) or
• Sebaceous skin, thick (oily or fatty skin) or
• Surgery on the face, history of—May increase risk for more serious side effects.

• Breathing problems (eg, asthma, emphysema) or
• Dysphagia (trouble swallowing) or
• Ptosis (droopy eyelid)—Use with caution. May make these conditions worse.

• Cow's milk protein allergy, history of or
• Infection at the injection site—Should not be used in patients with these conditions.

• If you have an allergy to abobotulinumtoxinA or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are allergic to milk, talk with the doctor.
• If you have an infection where the shot will be given.

This is not a list of all drugs or health problems that interact with Dysport.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Excessive doses of Dysport® may be expected to produce neuromuscular weakness with a variety of symptoms. Respiratory support may be required where excessive doses cause paralysis of 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 (5.2)]. Symptomatic treatment may be necessary.

Symptoms of overdose are likely not 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.

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/drug-service.html.

You should not receive Dysport injecton 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. Tell your doctor if you have ever had a side effect after receiving a botulinum toxin in the past

To make sure Dysport is safe for you, tell your doctor if you have:

• amyotrophic lateral sclerosis (ALS, or "Lou Gehrig's disease");

• myasthenia gravis;

• Lambert-Eaton syndrome;

• a breathing disorder such as asthma or emphysema;

• problems with swallowing;

• facial muscle weakness (droopy eyelids, weak forehead, trouble raising your eyebrows);

• a change in the normal appearance of your face;

• a seizure disorder;

• bleeding problems;

• heart disease;

• diabetes;

• if you have had or plan to have surgery (especially on your face); or

• if you have ever received other botulinum toxin injections such as Botox, Myobloc, or Xeomin (especially in the last 4 months).

AbobotulinumtoxinA is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

It is not known whether Dysport will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether abobotulinumtoxinA passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby while receiving Dysport.

Dysport is generally not used in children. However, this medicine may be used to treat lower limb muscle stiffness in children as young as 2 years old.

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.

Applies to abobotulinumtoxinA: intramuscular powder for solution

Along with its needed effects, abobotulinumtoxinA (the active ingredient contained in Dysport) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking abobotulinumtoxinA:

• Difficulty with swallowing or speaking
• hoarseness
• muscle or bone pain
• muscle weakness
• seizures
• sore throat
• voice changes

• Blistering, burning, crusting, dryness, or flaking of the skin
• body aches or pain
• chills
• cough
• cough producing mucus
• diarrhea
• difficult or labored breathing
• ear congestion
• fever
• general feeling of discomfort or illness
• headache
• itching, scaling, severe redness, soreness, or swelling of the skin
• joint pain
• loss of appetite
• loss of voice
• muscle aches and pains
• nausea
• shivering
• sneezing
• stiff muscles
• stuffy or runny nose
• sweating
• tightness in the chest
• trouble sleeping
• unusual tiredness or weakness
• vomiting

• Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• dizziness
• fast heartbeat
• flushing or redness of the skin
• hives, itching, rash
• partial or slight paralysis of the face
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• unusually warm skin

Some side effects of abobotulinumtoxinA may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• blurred vision
• decreased vision
• double vision
• dry eyes
• dry mouth
• eye pain
• itching of the eyes
• problems with focusing of the eyes
• seeing double

• Drooping upper eyelids
• pain or tenderness around the eyes and cheekbones

• Change in color vision
• difficulty seeing at night
• dizziness or lightheadedness
• feeling of constant movement of self or surroundings
• increased sensitivity of the eyes to sunlight
• sensation of spinning