onabotulinumtoxina

REMS

Botox Cosmetic

Treatment of the following conditions:
- Temporary improvement in the appearance of moderate to severe glabellar lines (brow furrow) associated with corrugator and/or procerus muscle activity in adults,
- Temporary improvement in the appearance of moderate to severe lateral canthal lines (crow's feet) associated with orbicularis oculi activity in adults,
- Temporary improvement in the appearance of moderate to severe forehead lines associated with frontalis muscle activity (should be treated in conjunction with glabellar lines).

Botox

Treatment of the following conditions:
- Spasticity,
- Cervical dystonia,
- Severe axillary hyperhidrosis that is refractory to topical agents,
- Blepharospasm associated with dystonia,
- Strabismus,
- Prevention of migraines in patients with chronic migraines (≥15 headaches/mo with headache lasting ≥4 hr/day),
- Urinary incontinence due to detrusor overactivity associated with a neurologic condition in adults who have an inadequate response to or are intolerant of an anticholinergic medication,
- Neurogenic detrusor overactivity in children ≥5 yr who have an inadequate response to or are intolerant of an anticholinergic medication,
- Overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

Action ⬆ ⬇

Produces partial chemical denervation by inhibiting the release of acetylcholine. Result is local decrease in muscle activity.

Therapeutic effects:

Decreased brow furrow, crow's feet, and forehead lines with improved appearance.
Decreased muscle tone in upper and lower limbs.
Decreased severity of abnormal head position and neck pain.
Decreased sweating.
Decreased blepharospasm.
Decreased strabismus.
Decreased frequency and duration of headaches.
Reduced frequency of urinary incontinence episodes.

Pharmacokinetics ⬆ ⬇

Absorption: Minimal systemic absorption; action is primarily local.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(improvement)

ROUTE	ONSET	PEAK	DURATION
IM‡	1–2 days	unknown	3–4 mo
IM‡	3–4 days	unknown	3–4 mo
IM*	2 wk	unknown	3–4 mo
IM‡‡	<2 wk	unknown	3–4 mo
IM**	1–2 days	unknown	2–6 wk
IM^	unknown	unknown	200 days
IM^^	unknown	unknown	3 mo

‡Cosmetic; ‡ Blepharospasm; * Cervical dystonia; ‡‡ Spasticity; ** Strabismus; ^ Axillary hyperhidrosis; ^^Migraines.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Presence of infection at planned injection sites;
Acute urinary tract infection and/or acute urinary retention (for urinary incontinence indication).

Use Cautiously in:

Peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, motor neuropathy) or neuromuscular junctional disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome) (↑ risk of significant systemic effects such as dysphagia or respiratory compromise);
Inflammation at planned injection site;
Marked facial asymmetry, ptosis, excessive dermatochelasis, deep dermal scarring, thick sebaceous skin, inability to lessen glabellar lines by physical spreading;
Excessive weakness or atrophy in target muscles;
Swallowing or breathing problems (for treatment of cervical dystonia; ↑ risk of dysphagia);
Respiratory problems (for treatment of spasticity or detrusor overactivity associated with a neurologic condition; ↑ risk of pulmonary infection and worsening condition);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children 2 yr (safety and effectiveness not established);
Geri: Use lowest effective dose in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: dry eye, eye irritation, photophobia, temporary eyelid droop, visual changes

GI: dysphagia, nausea

GU: urinary retention, urinary tract infection

Local: discomfort at injection sites, distant spread of toxin effect

MS: arthralgia, local muscle weakness, myalgia

Neuro: fatigue, headache

Resp: upper respiratory tract infection, bronchitis, dyspnea

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Neuromuscular effects may be potentiated by aminoglycosides, quinidine and other drugs that alter neuromuscular transmission.
Additive effects may occur with other forms of botulinum toxin.

Route/Dosage ⬆ ⬇

Reduction of Glabellar Lines

IM (Adults ): 0.1 mL (4 units) into each of five sites (two in each corrugator muscle and one in the procerus muscle; total dose of 20 units); not more frequently than every 3 mo.

Reduction of Lateral Canthal Lines

IM (Adults ): 0.1 mL (4 units) into each of three sites per side in the lateral orbicularis oculi muscle (12 units per side; total dose of 24 units); not more frequently than every 3 mo.

Reduction of Forehead Lines

IM (Adults ): 0.1 mL (4 units) into each of five sites in the frontalis muscle (total dose of 20 units); not more frequently than every 3 mo.

Upper Limb Spasticity

IM (Adults ): Biceps brachii: 60–200 units divided in 2–4 sites; not more frequently than every 3 mo; Brachioradialis: 45–75 units divided in 1–2 sites; not more frequently than every 3 mo; Brachialis: 30–50 units divided in 1–2 sites; not more frequently than every 3 mo; Pronator teres: 15–25 units in one site; not more frequently than every 3 mo; Pronator quadratus: 10–50 units in one site; not more frequently than every 3 mo; Flexor carpi radialis or flexor carpi ulnaris: 12.5–50 units in one site; not more frequently than every 3 mo; Flexor digitorum profundus or flexor digitorum sublimis: 30–50 units in one site; not more frequently than every 3 mo; Lumbricals/interossei: 5–10 units in one site; not more frequently than every 3 mo; Adductor pollicis or flexor pollicis longus: 20 units in one site; not more frequently than every 3 mo; Flexor pollicis brevis/opponens pollicis: 5–25 units in one site; not more frequently than every 3 mo.
IM (Children ≥2 yr): 3–6 units/kg divided among affected muscles, with the following doses being used for each muscle: Biceps brachii: 1.5–3 units/kg divided in 4 sites; not more frequently than every 3 mo; Brachialis, flexor carpi radialis or flexor carpi ulnaris: 1–2 units/kg divided in 2 sites; not more frequently than every 3 mo; Brachioradialis, flexor digitorum profundus or flexor digitorum sublimis: 0.5–1 units/kg divided in 2 sites; not more frequently than every 3 mo.

Lower Limb Spasticity

IM (Adults ): Gastrocnemius medial head, gastrocnemius lateral head, soleus, or tibialis posterior: 75 units divided in 3 sites; not more frequently than every 3 mo; Flexor hallucis longus or flexor digitorum longus : 50 units divided in 2 sites; not more frequently than every 3 mo.
IM (Children ≥2 yr): 4–8 units/kg divided among affected muscles, with the following doses being used for each muscle: Gastrocnemius, soleus, or tibialis posterior: 1–2 units/kg divided in 2 sites; may be repeated after 3 mo, based on return of symptoms.

Cervical Dystonia

IM (Adults ): Mean dose is 236 units divided among the affected muscles in patients previously treated with botulinum toxin; initial dose should be lower in previously untreated patients; subsequent dosing should be based on patient's head and neck position, localization of pain, muscle hypertrophy, patient response, and previous tolerability; total dose injected into sternocleidomastoid muscles should be ≤100 units (to ↓ incidence of dysphagia); not more frequently than every 3 mo.

Axillary Hyperhidrosis

IM (Adults ): 50 units per axilla; may repeat when clinical effect diminishes.

Blepharospasm

IM (Adults and Children ): 1.25–2.5 units into the medial and lateral pretarsal orbicularis oculi of the upper lid and into the lateral pretarsal orbicularis oculi of the lower lid; not more frequently than every 3 mo.

Strabismus

IM (Adults and Children ≥12 yr): Vertical muscles and for horizontal strabismus <20 prism diopters: 1.25–2.5 units in any one muscle; Horizontal strabismus of 20–50 prism diopters: 2.5–5 units in any one muscle; Persistent VI nerve palsy of ≥1 mo: 1.25–2.5 units in the medial rectus muscle.

Chronic Migraine

IM (Adults ): 155 units divided among seven specific head/neck muscle areas (see prescribing information for dose to be injected into each area) every 12 wk.

Urinary Incontinence

IM (Adults ): 200 units injected into the detrusor muscle; may repeat when clinical effect diminishes, but not more frequently than every 3 mo.

Overactive Bladder

IM (Adults ): 100 units injected into the detrusor muscle; may repeat when clinical effect diminishes, but not more frequently than every 3 mo.

Pediatric Detrusor Overactivity associated with a Neurologic Condition

IM (Children ≥5 yr and ≥34 kg): 200 units injected into the detrusor muscle; may repeat when clinical effect diminishes, but not more frequently than every 3 mo.
IM (Children ≥5 yr and <34 kg): 6 units/kg injected into the detrusor muscle; may repeat when clinical effect diminishes, but not more frequently than every 3 mo.

Availability ⬆ ⬇

Powder for injection (Botox Cosmetic): 50 units/vial ; 100 units/vial
Powder for injection (Botox): 100 units/vial ; 200 units/vial

Assessment ⬆ ⬇

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.

Implementation ⬆ ⬇

Clinicians administering botulinum toxin should understand neuromuscular anatomy of the area involved and potential alterations. Using Botox for unapproved uses may increase risks of adverse effects (excessive weakness, dysphagia, aspiration pneumonia); may be fatal.
- Botulinum toxin products are not interchangeable. Determine appropriate product prior to administration.
- Adults: Injections should be made no more frequently than every 3 mo and using the lowest effective dose. Do not exceed 400 units/3 mo.
- Children
  Total dose should not exceed the lower of 10 units/kg body weight or 340 units, in a 3-month interval. Total dose administered per treatment session in the upper limb should not exceed 6 units/kg or 200 units, whichever is lower. Total dose administered per treatment session in the lower limb should not exceed 8 units/kg or 300 units, whichever is lower.
Botox Cosmetic: Reconstitution: Reconstitute vial with 2.5 mL of 0.9% NaCl without preservatives for a concentration of 4 units/0.1 mL and a total treatment dose of 20 units in 0.5 mL. Inject diluent slowly into vial at a 45° angle. 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 4 hr of reconstitution; do not freeze. Discard unused solution. Unopened vials should be stored in refrigerator.
IM: Draw at least 0.5 mL of reconstituted solution into tuberculin syringe and expel any air bubbles from syringe barrel. Remove needle used for reconstitution and replace with a 30-gauge needle; ensure patency of needle. Inject each dose of 0.1 mL.
Botox: Reconstitution: Reconstitute vial with 2.5 mL of 0.9% NaCl without preservatives. Draw up amount of diluent in appropriate size syringe (see package insert). 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.
IM: Follow specific dose and administration recommendations for each indication.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇