No

Ophthalmic Agent, Toxin

Treatment of strabismus and blepharospasm associated with dystonia (including benign essential blepharospasm or VII nerve disorders in patients greater than or equal to 12 years of age)

Orphan drug: Treatment of dynamic muscle contracture in pediatric cerebral palsy patients

C

Hypersensitivity to botulinum A toxin; relative contraindications to botulinum toxin therapy include diseases of neuromuscular transmission and coagulopathy, including anticoagulant therapy; injections into the central area of the upper eyelid (rapid diffusion of toxin into the levator can occur resulting in a marked ptosis).

Use with caution in patients taking aminoglycosides or any other antibiotic or other drugs that interfere with neuromuscular transmission; do not exceed recommended dose

>10%: Ocular: Dry eyes, lagophthalmos, ptosis, photophobia, vertical deviation

1% to 10%:

Dermatologic: Diffuse rash

Ocular: Eyelid edema, blepharospasm

<1%: Ectropion, keratitis, diplopia, entropion

In the event of an overdosage or injection into the wrong muscle, additional information may be obtained by contacting Allergan Pharmaceuticals at (800)-347-5063 from 8 AM to 4 PM Pacific time, or at (714)-724-5954 at other times

Increased effect: Botulinum toxin may be potentiated by aminoglycosides

Keep in undiluted vials in freezer (at or below -5°C/23°F); administer within 4 hours after the vial is removed from the freezer and reconstituted; store reconstituted solution in refrigerator (2°C to 8°C/36°F to 46°F)

Botulinum A toxin 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. The antagonist muscle shortens simultaneously ("contracture"), taking up the slack created by agonist paralysis; following several weeks of paralysis, alignment of the eye is measurably changed, despite return of innervation to the injected muscle.

Strabismus: Onset of action: 1-2 days after injection; Duration of paralysis: 2-6 weeks

Blepharospasm: Onset: 3 days after injection; Peak: 1-2 weeks; Duration of paralysis: 3 months

Strabismus: 1.25-5 units (0.05-0.15 mL) injected into any one muscle

Subsequent doses for residual/recurrent strabismus: Re-examine patients 7-14 days after each injection to assess the effect of that dose. Subsequent doses for patients experiencing incomplete paralysis of the target may be increased up to two fold the previously administered dose. Maximum recommended dose as a single injection for any one muscle is 25 units.

Blepharospasm: 1.25-2.5 units (0.05-0.10 mL) injected into the orbicularis oculi muscle

Subsequent doses: Each treatment lasts approximately 3 months. At repeat treatment sessions, the dose may be increased up to twofold if the response from the initial treatment is considered insufficient (usually defined as an effect that does not last >2 months). There appears to be little benefit obtainable from injecting >5 units per site. Some tolerance may be found if treatments are given any more frequently than every 3 months.

The cumulative dose should not exceed 200 units in a 30-day period

Inject using a 27- to 30-gauge needle

None reported

None reported

No information available to require special precautions

No effects or complications reported

Patients with blepharospasm may have been extremely sedentary for a long time; caution these patients to resume activity slowly and carefully following administration

To alleviate spatial disorientation or double vision in strabismic patients, cover the affected eye; have epinephrine ready for hypersensitivity reactions

Injection: 100 units Clostridium botulinum toxin type A

Borodic GE and Pearce LB, "New Concepts in Botulinum Toxin Therapy," Drug Saf, 1994, 11(3):145-52.

Cohen S and Parkman HP, "Treatment of Achalasia - Whalebone to Botulinum Toxin," N Engl J Med, 1995, 332(12):815-6.

Ferrari AP, Jr, Siqueira ES, and Brant CQ, "Treatment of Achalasia in Chagas' Disease With Botulinum Toxin," N Engl J Med, 1995, 332(12):824-5.

Jankovic J and Brin MF, "Therapeutic Uses of Botulinum Toxin," N Engl J Med, 1991, 324(17):1186-94.

Pasricha PJ, Ravich WJ, Hendrix TR, et al, "Intrasphincteric Botulinum Toxin for the Treatment of Achalasia," N Engl J Med, 1995, 322(12):774-8.

Pasricha PJ, Ravich WJ, Hendrix TR, et al, "Treatment of Achalasia With Intrasphincteric Injection of Botulinum Toxin," Ann Intern Med, 1994, 121(8):590-1.

Repka MX, Savino PJ, and Reinecke RD, "Treatment of Acquired Nystagmus With Botulinum Neurotoxin A," Arch Ophthalmol, 1994, 112(10):1320-4.

Sheean GL, Murray NM, and Marsden CD, "Pain and Remote Weakness in Limbs Injected With Botulinum Toxin A for Writer's Cramp," Lancet, 1995, 346(8968):154-6.