incobotulinumtoxinA

onabotulinumtoxinA (Toxin type A)

Botox, Botox Cosmetic, Vistabel (UK), Xeomin (UK)

abobotulinumtoxinA (Toxin type A)

Dysport

incobotulinumtoxinA (Toxin type A)

Xeomin

rimabotulinumtoxinB (Toxin type B)

Myobloc, NeuroBloc (UK)

Pharmacologic class: Neurotoxin

Therapeutic class: Neuromuscular blocker

Pregnancy risk category C

Toxin type A (onabotulinumtoxinA)

Toxin types A and B (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, rimabotu-linumtoxinB)

Toxin type A (onabotulinumtoxinA) when administered for eye disorders

Toxin type A (abobotulinumtoxinA)

Toxin type B (rimabotulinumtoxinB)

FDA Box Warning

• Postmarketing reports indicate that the effects of all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects, including asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These signs and symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life-threatening, and deaths have occurred.

• The risk of signs and symptoms is probably greatest in children treated for spasticity, but signs and symptoms can also occur in adults treated for spasticity and other conditions, particularly in 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 dosages comparable to those used to treat cervical dystonia and at lower dosages.

Action

Blocks neuromuscular transmission by binding to receptor sites on motor nerve terminals and inhibiting acetylcholine release, thereby causing localized muscle denervation. As a result, local muscle paralysis occurs, which leads to muscle atrophy and reinnervation due to development of new acetylcholine receptors.

Availability

Toxin type A-(onabotulinumtoxinA)

Powder for injection: 100 units/vial

Toxin type A-abobotulinumtoxinA

Freeze-dried powder for injection: 300 units/vial, 500 units/vial

Toxin type A-(incobotulinumtoxinA)

Powder for injection, lyophilized: 50 units in single-use vials, 100 units in single-use vials

Toxin type B-(rimabotulinumtoxinB)

Solution for injection: 5,000-units/ml vial

Indications and dosages

Toxin type A (onabotulinumtoxinA)

Temporary improvement in appearance of moderate to severe glabellar lines associated with corruga-tor or procerus muscle activity

Adults ages 65 and younger: Botox cosmetic only-Total of 20 units (0.5-ml solution) injected I.M. as divided doses of 0.1 ml into each of five sites: two in each corrugator muscle and one in procerus muscle. Injection usually needs to be repeated q 3 to 4 months to maintain effect. Dysport-50 units I.M. in five equal aliquots of 10 units each to achieve clinical effect

Xeomin-Or, 20 units per treatment session divided into five equal I.M. injections of 4 units each.

Treatment of blepharospasm in patients previously treated with onabotulinumtoxinA (Botox)

Adults: Xeomin-When initiating therapy, base dose, number, and location of injections on the previous dosing of onabotulinumtoxinA (Botox). If previous dose of Botox isn't known, the recommended starting dose is 1.25 to 2.5 units per injection site.

Upper limb spasticity

Adults: Botox-75 to 360 units I.M. divided among selected muscles at a given treatment session. Dose can be repeated no sooner than 12 weeks after the previous injection.

Prophylaxis of headaches in patients with chronic migraine (15 or more days per month with headache lasting 4 hours a day or longer)

Adults: Botox-155 units as 0.1-ml (5 units) injections per each site divided across seven head and neck muscles

Severe axillary hyperhidrosis inadequately managed by topical agents

Adults: Botox-50 units per axilla injected into defined hyperhidrotic area

Blepharospasm

Adults: 1.25 to 2.5 units injected into medial and lateral pretarsal orbicularis oculi of upper eyelid and lateral pretarsal orbicularis oculi of lower eyelid

Strabismus

Adults: 1.25 to 5 units injected into eyelid (dosage varies with strabismus severity). Dose can be repeated in 7 to 14 days if patient has adequate response; with inadequate response, dosage may be doubled.

Toxin types A and B (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, rimabotu-linumtoxinB)

Treatment of cervical dystonia to decrease severity of abnormal head position and neck pain in both botulinum toxin-naïve and previously treated patients

Adults: Xeomin-120 units injected I.M. into affected muscles per treatment session.

To relax skeletal muscles and reduce severity of abnormal head position and neck pain associated with cervical dystonia

Adults: Botox-Usual dosage is 236 units injected I.M. locally into affected muscles. Dosage ranges from 198 to 300 units. Dysport-500 units I.M. as a divided dose among affected muscles in patients with or without a history of prior treatment with botulinum toxin.

Myobloc-2,500 to 5,000 units I.M. injected locally into affected muscles.

Contraindications

• Hypersensitivity to drug or its components

• Allergy to cow's-milk protein (Dysport)

• Acute urinary tract infection or acute urinary retention (Botox intradetrusor injections)

• Active infection at injection site

Precautions

Use cautiously in:

• cardiovascular disease, peripheral neuropathy, neuromuscular disorders, compromised respiratory function, dysphagia

• inflammation at injection site, injections near vulnerable anatomical structures

• pregnant or breastfeeding patient

• children younger than age 12; children younger than age 18 (Dysport, Xeomin)

Administration

• Be aware that only trained professional medical personnel should inject this drug.

• Be aware that botulinum toxin products aren't interchangeable.

Toxin type A (onabotulinumtoxinA) when administered for eye disorders

• Reconstitute by slowly injecting preservative-free normal saline solution into drug vial.

• Rotate vial gently to mix drug; then draw up at least 20 units (0.5-ml solution) and expel air bubbles.

• Remove needle used for reconstitution, and attach 30G needle. Then inject drug as divided doses of 0.1 ml into each of five sites (two in each corruga-tor muscle, one in procerus muscle).

• Prepare eye with several drops of local anesthetic and ocular decongestant, as prescribed, several minutes before injection for blepharospasm or strabismus.

• When administering for upper limb spasticity, dilute with preservative-free normal saline solution to 200 units/4 ml or 100 units/2 ml. Then, using a 25G to 30G needle for superficial muscles and a longer 22G needle for deeper musculature, inject no more than 50 units per site.

Toxin type A (abobotulinumtoxinA)

• Reconstitute each 300-unit vial with 0.6 ml preservative-free normal saline solution and each 500-unit vial with 1 ml preservative-free normal saline solution.

• Swirl vial gently to mix drug.

• Remove needle used for reconstitution. Use a 23G to 25G needle for administration. Then inject 10 units into each of five sites (two in each corrugator muscle and one in the procerus muscle).

• Use within 4 hours of reconstitution.

Toxin type B (rimabotulinumtoxinB)

• Draw up prescribed dose from preservative-free, 3.5-ml single-use vial.

• Don't shake vial.

• Divide prescribed dose and inject locally into affected muscles.

Adverse reactions

CNS: headache, dizziness

CV: hypertension, arrhythmias, myocardial infarction (MI)

EENT: blepharoptosis, conjunctivitis, keratitis, eye dryness, double vision, tearing, increased sensitivity to light, sinusitis, pharyngitis

GI: nausea, dyspepsia, difficulty swallowing

Musculoskeletal: back pain, neck pain, muscle weakness

Respiratory: pneumonia, bronchitis, upper respiratory tract infection

Skin: skin tightness, ecchymosis

Other: tooth disorder, injection site redness, edema, or pain, flulike symptoms, facial muscle paralysis, infection, anaphylaxis

Interactions

Drug-drug. Aminoglycosides, anticholinesterase compounds, clindamycin, lincomycin, magnesium sulfate, other neuromuscular blockers (such as succinylcholine), polymyxin B, quinidine: increased risk of adverse effects

Patient monitoring

• Stay alert for signs and symptoms of anaphylaxis, particularly after first dose.

• Monitor vital signs and ECG, watching for evidence of hypertension, arrhythmias, and MI.

• Assess effect of drug on affected muscles; check for paralysis.

Be aware that spread of toxin effects may lead to swallowing and breathing difficulties and death. Provide immediate medical attention if respiratory, speech, or swallowing difficulties occur.

• Monitor temperature. Watch for signs and symptoms of respiratory and EENT infections as well as flulike symptoms.

Patient teaching

Instruct patient to seek immediate medical attention if respiratory, speech, or swallowing difficulties occur.

• Teach patient about desired effect of injection. Advise patient to report paralysis.

• Instruct patient to report signs and symptoms of infection, particularly flulike illness and EENT and respiratory infections.

• Inform patient being treated for ble-pharospasm (uncontrollable blinking) that he may experience transient eyelid drooping, corneal inflammation, double vision, dry eyes, tearing, and light sensitivity.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

incobotulinumtoxinA

(in-koe-bot-ue-li-num-tox-in-A) ,

Xeomin

(trade name)

Classification

Therapeutic: antispasticity agents
Pharmacologic: neurotoxins
Pregnancy Category: C

Indications

Treatment of cervical dystonia in adults.Treatment of blepharospasm in adults who had prior treatment with onabotulinumtoxinA.Temporary improvement of moderate to severe glabellar (frown) lines in adults.

Action

Inhibits release of acetylcholine from peripheral cholinergic nerve endings, resulting chemical denervation of treated muscle.

Therapeutic effects

Localized reduction of muscle activity, with decrease in spasticity, abnormal head position and neck pain related to cervical dystonia.
Decreased appearance of blepharospasm or glabellar lines.

Pharmacokinetics

Absorption: Minimal but may be significant in selected populations.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: Unknown.

Time/action profile (improvement in spasticity/appearance of lines)

ROUTEONSETPEAKDURATION
IMwithin 1 wk†unknownup to 4 mo
†For blepharospasm, may be up to 4 wk for other indications.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to botulinum toxin products or additives ; Infection at injection site.
Use Cautiously in: Previous surgical facial alterations, marked facial asymmetry, known weakness/atrophy of muscle in question, inflammation or skin abnormality at injection site, ptosis; Compromised respiratory function or dysphagia; Peripheral motor neuropathic disorders (may exacerbate clinical effects and ↑ the risk of severe dysphagia and respiratory compromise); Hyperhydrosis (safety not established); Blepharospasm—if diplopia occurs, lower lid injection should not be repeated); Cervical dystonia— patients with smaller neck muscle mass and those requiring bilateral sternocledomastoid injections (↑ risk of dysphagia, smaller doses may be necessary); Glabellar lines—ptosis may occur; Geriatric: Use cautiously; consider concurrent diseases and drug therapy; Obstetric: Use in pregnancy only if potential benefit justifies potential risk to fetus; Pediatric: Safety and effectiveness has not been established.

Adverse Reactions/Side Effects

Blepharospasm

Central nervous system

  • headache (most frequent)

Ear, Eye, Nose, Throat

  • ptosis (most frequent)
  • dry eye (most frequent)
  • impaired vision (most frequent)
  • nasopharyngitis (most frequent)
  • ↓ blinking
  • corneal exposure/ulceration
  • diplopia

Gastrointestinal

  • diarrhea (most frequent)
  • dry mouth (most frequent)
  • dyspepsia (most frequent)

Miscellaneous

  • allergic reactions, including anaphylaxis
  • spread of toxin effect (life-threatening)
  • flu-like symptoms

Cervical dsytonia

Gastrointestinal

  • dysphagia (most frequent)

Local

  • injection site pain (most frequent)

Musculoskeletal

  • muscle weakness (most frequent)
  • musculoskeletal pain (most frequent)
  • neck pain (most frequent)

Miscellaneous

  • allergic reactions, including anaphylaxis
  • spread of toxin effect (life-threatening)
  • flu-like symptoms

Glabellar lines

Central nervous system

  • headache (most frequent)

Local

  • injection site pain/reaction

Miscellaneous

  • allergic reactions, including anaphylaxis
  • spread of toxin effect (life-threatening)
  • flu-like symptoms

Interactions

Drug-Drug interaction

Concurrent use of aminoglycosides, or agents interfering with neuromuscular transmission including curare-like agents or muscle relaxants may ↑ effect. Concurrent use of anticholinergics ↑ systemic anticholinergic effects.

Route/Dosage

Note: Doses are NOT interchangeable with other botulinumtoxin products.

Blepharospasm

Intramuscular (Adults) Dose, number of injections and location is based on previous dosing of onabotulinumtoxinA (Botox), if this is unknown then initial dose is 1.25–2.5 Units/site; (mean dose is 5.6 Units/injection site, 6 injections/eye).

Cervical dystonia

Intramuscular (Adults) 120 Units total/treatment session; dose, number and location based on number and location of involved sites.

Glabellar lines

Intramuscular (Adults) 20 Units/session consisting of 5 injections (2 in each corrugator muscle, one in the procerus muscle) of 4 units apiece. Not to be repeated more frquently than every 3 mo.

Availability

Lyophilized powder for local injection (requires reconstitution): 50 Units/vial, 100 Units/vial

Nursing implications

Nursing assessment

  • Assess effects of injection. Effects occur within 7 days and usually last up to 3 mo; may be longer or shorter in each individual.
  • Assess for signs of anaphylactic reaction (dyspnea, rash, pruritus, laryngeal edema, wheezing) following administration. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
  • Monitor for asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. Medication may spread from the injection site to distant parts of the body.

Potential Nursing Diagnoses

Disturbed body image (Indications)
Impaired physical mobility (Indications)

Implementation

  • Clinicians administering incobotulinumtoxinA should understand neuromuscular anatomy of the area involved and potential alterations.
    • Botulinum toxin products are not interchangeable. Determine appropriate product prior to administration.
    • Injections should be made no more frequently than every 3 mo and using the lowest effective dose.
  • Reconstitute vial with 0.9% NaCl without preservatives according to package insert. Gently inject diluent slowly into vial. Discard vial if vacuum does not pull diluent into vial. Rotate vial gently and record date and time of reconstitution on label. Solution should be clear, colorless, and free of particulate matter. Refrigerate solution and use within 24 hr of reconstitution; do not freeze. Discard unused solution. Unopened vials should be stored in refrigerator.
  • Intramuscular: Follow specific dose and administration recommendations for each indication.

Patient/Family Teaching

  • Review Medication Guide with patient prior to each administration.
  • Inform patient that the material has the potential to spread from the injection site to distant parts of the body. May occur within hrs or several wks after injection. Advise patient or caregiver to notify health care professional immediately if swallowing, speech, or respiratory disorders arise.
  • May cause loss of strength, muscle weakness, blurred vision, or drooping eyelids. Caution patient to avoid driving or other activities requiring alertness and dexterity until response to injection is known.
  • Advise sedentary or previously immobile patients to gradually resume activities after injection for cervical dystonia or blephrospasm.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • ↓ brow furrow.
  • ↓ muscle tone in upper limbs.
  • ↓ severity of abnormal head position and neck pain.
References in periodicals archive ?
The sBLA is based on a Phase III randomized, double-blind, placebo-controlled, multicenter 184 subject trial, which met both of its co-primary endpoints for subjects administered 100 U incobotulinumtoxinA by achieving statistically significant change in unstimulated salivary flow rate, and in the subjects' Global Impression of Change Scale.
He typically injects a medium dose of one of three neuromodulators--such as 6-10 U of onabotulinumtoxinA (Botox), 6-10 U of incobotulinumtoxinA (Xeomin) or 14-18 U of abobotulinumtoxinA (Dysport).