AbobotulinumtoxinA

Name: AbobotulinumtoxinA

What is abobotulinumtoxinA (Dysport)?

AbobotulinumtoxinA (Dysport), also called botulinum toxin type A, is made from the bacteria that causes botulism. Botulinum toxin blocks nerve activity in the muscles, causing a temporary reduction in muscle activity.

Dysport is used to treat cervical dystonia (severe spasms in the neck muscles). Dysport is also used to treat muscle spasms (stiffness) in the upper limbs (elbows, wrists, fingers) or lower limbs (ankles, toes).

Dysport is also used to temporarily lessen the appearance of facial wrinkles.

Dysport may also be used for purposes not listed in this medication guide.

What should I discuss with my healthcare provider before I receive 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. 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.

AbobotulinumtoxinA dosing information

Usual Adult Dose for Cervical Dystonia:

500 units IM given as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin

Below is a description of the average dose, as well as the minimum and maximum dose injected into specific muscles in the pivotal clinical trials:
MUSCLE: MEDIAN DOSE (MINIMUM & MAXIMUM DOSE):
-Sternocleidomastoid: 125 Units (50, 350)
-Splenius capitis: 200 Units (75, 450)
-Trapezius: 102.6 Units (50, 300)
-Levator scapulae: 105.3 Units (50, 200)
-Semispinalis capitis: 131.6 Units (50, 250)
-Longissimus: 150 Units (100, 200)

Comments:
-Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.
-Studies with this drug in cervical dystonia suggest that the peak effect occurs between 2 and 4 weeks after injection.
-Simultaneous EMG-guided application of this drug may be helpful in locating active muscles not identified by physical examination alone.
-Where dose modification is necessary for the treatment of cervical dystonia, studies suggest that dose adjustment can be made in 250 unit steps according to the individual patient's response, with retreatment every 12 weeks or longer, based on return of clinical symptoms. Studies also suggest that the total dose administered in a single treatment should be between 250 units and 1000 units.
-Retreatment, if needed, should not occur in intervals of less than 12 weeks.
-Doses above 1000 Units have not been evaluated.
-The starting dose of 500 units recommended for cervical dystonia is applicable to adults of all ages.

Use: For the treatment of adults with cervical dystonia

Usual Adult Dose for Glabellar Lines:

50 units divided into 5 equal aliquots of 10 units each, should be administered to affected muscles to achieve clinical effect

Comments:
-The clinical effect of this drug may last up to 4 months.
-Repeat dose studies demonstrated continued efficacy with up to 4 repeated administrations.
-This drug should be administered no more frequently than every 3 months. -When used for re-treatment, this drug should be reconstituted and injected using the same techniques as the initial treatment.

Use: For the temporary improvement in the appearance of moderate to severe glabellar lines associated with procerus and corrugator muscle activity in adult patients less than 65 years of age

Usual Adult Dose for Upper Limb Spasticity:

Dosing in initial and subsequent treatment sessions should be tailored to the individual based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient response to previous treatment, and/or adverse event history with this drug.

IN A CLINICAL TRIAL, DOSES OF 500 UNITS AND 1000 UNITS WERE DIVIDED AMONG SELECTED MUSCLES, AS SHOWN BELOW:
MUSCLES INJECTED/RECOMMENDED DOSE/RECOMMENDED NUMBER OF INJECTIONS PER MUSCLE:
-Flexor carpi radialis (FCR)/ 100 to 200 Units/1 to 2 injections
-Flexor carpi ulnaris (FCU)/ 100 to 200 Units/1 to 2 injections
-Flexor digitorum profundus (FDP)/100 to 200 Units/1 to 2 injections
-Flexor digitorum superficialis (FDS)/100 to 200 Units/1 to 2 injections
-Brachialis/200 to 400 Units/1 to 2 injections
-Brachioradialis/100 to 200 Units/1 to 2 injections
-Biceps Brachii (BB)/200 to 400 Units/1 to 2 injections
-Pronator Teres/100 to 200 Units/1 injection

Comments:
-No more than 1 mL should generally be administered at any single injection site.
-Repeat treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection.
-A majority of patients in clinical studies were retreated between 12 and 16 weeks; however some patients had a longer duration of response (i.e., 20 weeks). -The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose and muscles to be injected.
-Improvement may be expected one week after administration.

Use: For the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors, and finger flexors

AbobotulinumtoxinA Dosage and Administration

General

  • Individualize dosage according to patient response and particular condition treated.384 385

  • Do not exceed recommended dose and frequency; excessive and/or unintended neuromuscular weakness may occur if higher than recommended dosages are given.384 Use minimum effective dosage whenever possible to reduce risk of adverse effects.384 388

Administration

IM Administration

Administer by IM injection into affected muscles.384

Instructions for reconstitution and administration are specific to each vial size and condition being treated; consult manufacturer's labeling for detailed instructions regarding reconstitution, preparation, and administration.384

Monitor patients for respiratory distress or other possible adverse effects related to spread of botulinum toxin (e.g., dysphagia, dysphonia, unexpected muscle weakness, urinary incontinence, ptosis, double vision, blurred vision, dysarthria).381 384 (See Distant Spread of Toxin Effects under Cautions.)

Reconstitution

For cervical dystonia, reconstitute vial labeled as containing 300 or 500 units of lyophilized drug with 0.6 or 1 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 250 units per 0.5 mL or 500 units per mL, respectively.384 Gently rotate vial until powder is completely dissolved.384

For glabellar facial lines, reconstitute vial labeled as containing 300 units of abobotulinumtoxinA with 1.5 or 2.5 mL of preservative-free 0.9% sodium chloride injection to provide a solution containing 10 units per 0.05 mL or 10 units per 0.08 mL, respectively.384 Use a 21-gauge needle to draw an appropriate amount of diluent into a syringe.384 Insert needle into drug vial at a 45° angle and allow partial vacuum to draw in diluent; do not use vial if vacuum is absent.384 Gently rotate vial until powder is completely dissolved.384

Use reconstituted solutions immediately or store at 2–8°C for up to 4 hours.384 Carefully discard any unused portions as medical waste.384

Injection Techniques (Cervical Dystonia)

Administer total dose per treatment session as several injections divided among affected muscles.384 Use a sterile 23- or 25-gauge needle.384

EMG-guided injections may be helpful in locating target injection sites, particularly for muscles that are difficult to identify by physical examination alone.384

Injection Techniques (Glabellar Facial Lines)

Identify injection sites by palpating for areas of tense muscle mass in the lateral corrugator and vertical procerus muscles while patient is frowning; location, size, and use of such muscles may vary considerably among individuals.384

Administer using a 30-gauge needle.384 Apply digital pressure to superior medial orbital rim while injecting through skin.384

Injections into the medial corrugator muscle should be ≥1 cm above the supraorbital ridge and should not be injected <1 cm above the central eyebrow.384

Avoid injections near the levator palpebrae superioris, especially in individuals with larger brow-depressor complexes.384

Dosage

Potency of abobotulinumtoxinA expressed in units of biologic activity; each unit is equivalent to the median intraperitoneal lethal dose (LD50) in mice.384 385 393 399

Assay methods used to determine potency of various botulinum toxin preparations are specific to each individual preparation; units of biologic activity of abobotulinumtoxinA cannot be compared with or converted to units of other botulinum toxin preparations.381 384 385 391 396 397 399

Adults

Cervical Dystonia IM

Toxin-naive and previously treated patients: Initially, 500 units as a divided dose among affected muscles.384

In clinical studies, median initial doses injected into the sternocleidomastoid, splenius capitis, trapezius, levator scapulae, scalenus (medius and anterior), semispinalis capitis, and longissimus muscles were 125 units (range 50–350), 200 units (range 75–450), 102.6 units (range 50–300), 105.3 units (range 50–200), 115.5 units (range 50–300), 131.6 units (range 50–250), and 150 units (range 100–200), respectively.384

Adjust total dosage administered in subsequent treatment sessions by increments of 250 units based on patient response.384

Usual duration of response 12–16 weeks or longer; may repeat treatments every 12–16 weeks or longer if symptoms return.384

Glabellar Facial Lines IM

Manufacturer recommends a total dose of 50 units per treatment session, administered as 10 units (0.05 or 0.08 mL depending on concentration of reconstituted solution) into each of 5 sites: 2 in each corrugator muscle and one in procerus muscle.384

Cosmetic effects usually persist for up to 4 months.384 393 May repeat treatments at intervals of ≥3 months.384

Variable dosing based on gender and muscle mass also has been used in clinical practice.397 Higher doses generally recommended in men versus women due to greater muscle mass in men.397

Prescribing Limits

Adults

Cervical Dystonia IM

Dosage range was 250–1000 units per single treatment session in uncontrolled, open-label clinical studies; safety and efficacy of doses >1000 units not established.384 387

Limit total dose injected into sternocleidomastoid muscle to minimize risk of dysphagia.384 (See Dysphagia/Breathing Difficulties under Cautions.)

Do not repeat treatments more frequently than once every 12 weeks.384

Glabellar Facial Lines IM

Do not repeat treatments more frequently than once every 3 months.384

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.384 (See Geriatric Use under Cautions.)

What do I need to tell my doctor BEFORE I take AbobotulinumtoxinA?

  • 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 abobotulinumtoxinA.

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.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Very bad muscle pain or weakness.
  • Change in eyesight, eye pain, or very bad eye irritation.
  • Low mood (depression).
  • Seizures.
  • Blood in the urine.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about abobotulinumtoxinA, please talk with the doctor, pharmacist, or other health care provider.
  • 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about abobotulinumtoxinA. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using abobotulinumtoxinA.

Review Date: October 4, 2017

Pronunciation

(aye bo BOT yoo lin num TOKS in aye)

Pharmacologic Category

  • Neuromuscular Blocker Agent, Toxin

Pharmacology

AbobotulinumtoxinA (previously known as botulinum toxin type A) is a neurotoxin produced by Clostridium botulinum, spore-forming anaerobic bacillus, which appears to affect only the presynaptic membrane of the neuromuscular junction in humans, where it prevents calcium-dependent release of acetylcholine and produces a state of denervation. Muscle inactivation persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle-cell walls.

Absorption

Not expected to be present in peripheral blood at recommended doses following intramuscular (IM) injection

Onset of Action

Peak effect: Cervical dystonia: 2 to 4 weeks; Upper limb spasticity: 1 week

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Usual Adult Dose for Cervical Dystonia

500 units IM given as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin

Below is a description of the average dose, as well as the minimum and maximum dose injected into specific muscles in the pivotal clinical trials:
MUSCLE: MEDIAN DOSE (MINIMUM & MAXIMUM DOSE):
-Sternocleidomastoid: 125 Units (50, 350)
-Splenius capitis: 200 Units (75, 450)
-Trapezius: 102.6 Units (50, 300)
-Levator scapulae: 105.3 Units (50, 200)
-Semispinalis capitis: 131.6 Units (50, 250)
-Longissimus: 150 Units (100, 200)

Comments:
-Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.
-Studies with this drug in cervical dystonia suggest that the peak effect occurs between 2 and 4 weeks after injection.
-Simultaneous EMG-guided application of this drug may be helpful in locating active muscles not identified by physical examination alone.
-Where dose modification is necessary for the treatment of cervical dystonia, studies suggest that dose adjustment can be made in 250 unit steps according to the individual patient's response, with retreatment every 12 weeks or longer, based on return of clinical symptoms. Studies also suggest that the total dose administered in a single treatment should be between 250 units and 1000 units.
-Retreatment, if needed, should not occur in intervals of less than 12 weeks.
-Doses above 1000 Units have not been evaluated.
-The starting dose of 500 units recommended for cervical dystonia is applicable to adults of all ages.

Use: For the treatment of adults with cervical dystonia

Usual Adult Dose for Upper Limb Spasticity

Dosing in initial and subsequent treatment sessions should be tailored to the individual based on the size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness, the patient response to previous treatment, and/or adverse event history with this drug.

IN A CLINICAL TRIAL, DOSES OF 500 UNITS AND 1000 UNITS WERE DIVIDED AMONG SELECTED MUSCLES, AS SHOWN BELOW:
MUSCLES INJECTED/RECOMMENDED DOSE/RECOMMENDED NUMBER OF INJECTIONS PER MUSCLE:
-Flexor carpi radialis (FCR)/ 100 to 200 Units/1 to 2 injections
-Flexor carpi ulnaris (FCU)/ 100 to 200 Units/1 to 2 injections
-Flexor digitorum profundus (FDP)/100 to 200 Units/1 to 2 injections
-Flexor digitorum superficialis (FDS)/100 to 200 Units/1 to 2 injections
-Brachialis/200 to 400 Units/1 to 2 injections
-Brachioradialis/100 to 200 Units/1 to 2 injections
-Biceps Brachii (BB)/200 to 400 Units/1 to 2 injections
-Pronator Teres/100 to 200 Units/1 injection

Comments:
-No more than 1 mL should generally be administered at any single injection site.
-Repeat treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection.
-A majority of patients in clinical studies were retreated between 12 and 16 weeks; however some patients had a longer duration of response (i.e., 20 weeks). -The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose and muscles to be injected.
-Improvement may be expected one week after administration.

Use: For the treatment of upper limb spasticity in adult patients, to decrease the severity of increased muscle tone in elbow flexors, wrist flexors, and finger flexors

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