Botox

Generic Name: Botulinum toxin type A
Product Name: Botox

Indication

Botox is a medication used to treat neuromuscular conditions (conditions affecting the nerves and muscles). It is used for both therapeutic and cosmetic purposes.

Botox is used for:

• Chronic migraine prophylaxis (prevention) in adults who experience headaches on ≥ 15 days per month, of whcih ≥ 8 days per month are migraine-type headaches;
• Strabismus (a condition in which the eyes look in the wrong direction) in adults and children;
• Blepharospasm (spasms in eyelid muscles) related to lack of muscle tone in adults and children ≥ 12 years. This includes facial nerve disorders, particularly hemifacial spasm (spasms on one side of the face);
• Cervical dystonia (lack of tone in neck muscles) and spasmodic torticollis (involuntary contraction of neck muscles);
• Focal spasticity (constant and involuntary muscle contraction) in the upper and lower limbs, including dynamic equinus due to cerebral palsy in children ≥ 2 years;
• Focal spasticity in adults;
• Severe underarm sweating, also known as primary or focal hyperhidrosis;
• Laryngeal dystonia (involuntary movement of laryngeal muscles, also known as spasmodic dysphonia).

Botox is also used for the temporary cosmetic improvement of facial wrinkles in adults, including:¹

• Crow’s feet;
• Forehead lines; and
• Vertical wrinkles between the eyebrows (glabellar lines).

Action

Botulinum toxin is a neuromuscular agent, that is, a medication that affects the nerves and muscles, and specifically blocks neuromuscular conduction (the conduction of nerve impulses). Botulinum toxin causes this effect by binding to motor or parasympathetic nerve terminal receptors (the nerve endings that receive nerve impulses) and blocking neuromuscular conduction. Botulinum toxin causes chemical denervation (removal of nerve sensations) of the target muscle by blocking the release of the neurotransmitter acetylcholine, when injected intramuscularly.  The result is temporary and causes reversible muscle paralysis, which prevents involuntary muscle contractions or spasms.

Intradermal injection (injection to the dermal layer of skin) in the armpit produces chemical denervation of the sweat glands and a reduction in sweating.

Dose advice

Dose information

Individuals who have received a Botox injection should seek medical attention immediately if they experience difficulty speaking, swallowing or breathing, as these side effects may be life threatening. When used for the treatment of cervical dystonia, Botox therapy comes with the possible risk of difficulty swallowing. In some cases this condition is serious, and rarely may require gastric tube placement. There is also the potential for Botox to induce general malaise, which may last up to 6 weeks, and individuals receiving Botox therapy should be aware of this possible side effect.

For some individuals who were previously sedentary, Botox therapy may enable them to resume activity. It is important that activity is resumed gradually.

At least 3 months must elapse between Botox injections, or between a Botox injection and injection of another medication containing botulinum toxin, the active ingredient in Botox.

Botox is administered by injection, and the correct dose depends on the condition or cosmetic use for which the injection is given. A doctor will determine and administer the correct starting dose. The dose may change between treatment sessions, depending on how the individual’s condition responds to the treatment. The injection sites for Botox vary depending on the condition being treated.

Blepharospasm and VIIth nerve disorders (hemifacial spasm)

When used to treat blepharospasm, Botox is injected intramuscularly, into the orbicularis oculi (the muscle that closes the eyelid) of the upper and lower eyelid.

Individuals receiving Botox therapy for VIIth nerve disorders, including hemifacial spasms, will also receive injections at these sites. Additional injections may be administered at the following sites, depending on the extent and site of the spasm:

• Corrugator supercilii (the muscle that wrinkles the brow);
• Zygomaticus major (a muscle involved in facial expression, particularly smiling);
• Orbicularis oris (a muscle encircling the mouth that controls movement of the lips); and/or
• Other facial muscles.

Strabismus

For treatment of strabismus, Botox is injected into the muscles surrounding the eye. The injection site will depend on which muscles are involved and the extent of the individual’s visual deviations. The doctor will prepare the eye for the injection by administering local anaesthetic drops and an ocular decongestant (to reduce inflammation).

The aim of Botox treatment for strabismus is to paralyse the injected muscles. The doctor may monitor individuals for up to 2 weeks following the injection, to assess how much muscle paralysis was achieved by the treatment, and if the dose of Botox needs to be modified. Individuals who do not achieve adequate muscle paralysis with the starting dose are likely to have the dose increased for subsequent treatments. It may be necessary to cover the treated eye following injection to reduce spatial disorientation, double vision or past pointing.

Focal spasticity in the upper and lower limbs, including equinus foot disorder

For children, the dose and number of injection sites will depend upon the muscles involved, the severity of spasticity, the presence or absence of local muscle weakness, and the child’s response to previous treatment. Injections are typically administered to:

• Upper limb muscles;
• Lower limb muscles;
• Gastrocnemius muscle (for equinus foot disorder).

For adults, the dose and number of injection sites will vary depending on the severity of spasms and the size, number and location of muscles involved. When large muscles are involved, treatment is often more effective if multiple injections are made into the same muscle.

Cervical dystonia

For the treatment of cervical dystonia, the correct dose of Botox will vary depending on:

• Position of the head and neck;
• Pain;
• Muscle hypertrophy;
• Body weight;
• Response to previous treatments.

The number of injection sites will depend on the size of the muscle to be denervated. For large muscles, multiple injection sites may be used. Botox is typically injected to one or more of the following muscles:

• Sternocleidomastoid (two muscles controlling rotation of the head from side to side);
• Levator scapulae (the muscle that raises the bone of the shoulder blade);
• Scalene (the muscles controlling movement of the neck from side to side);
• Splenius capitis (the muscle connecting the base of the skull to the upper vertebrae of the neck);
• Trapezius (a large muscle in the upper back near the shoulder blades).

Primary hyperhidrosis of the axillae

Treatment of hyperhidrosis usually involves 10–15 injections into the skin of the armpit.

Spasmodic dysphonia

Patients with spasmodic dysphonia are typically injected once into each thyroarytenoid muscle (controlling relaxation and shortening of the vocal cords).

For spasmodic dysphonia involving abductor muscles (controlling movement of the limbs away from the midline of the body), Botox is injected into one posterior cricoarytenoid (a muscle in the larynx that opens the vocal chords).

Chronic migraine

For prevention of chronic migraine, Botox is injected into seven muscles in the head and neck region. If one particular region of the head or neck is particularly involved in migraine pain, additional injections may be administered to the muscles affecting pain oin that area.

Cosmetic applications

• Glabellar lines: To cosmetically correct glabellar lines, up to five injections are administered into each corrugator muscle, and a further injection is administered into the procerus muscle (running across the bridge of the nose).
• Crow’s feet: To improve the appearance of crow’s feet, Botox is injected three times into each lateral orbicularis oculi (eye muscles).
• Forehead lines: To improve the appearance of forehead lines, Botox is injected into four sites in the frontalis muscle (running over the forehead to the upper eyebrow), about 2–3 cm above the eyebrow. The injections are usually placed at 1–2 cm intervals along a deep forehead crease.

Contraindications

Botox should not be used by individuals with the following conditions:

• Known hypersensitivity to any ingredient in the preparation;
• Myasthenia gravis;
• Eaton-Lambert syndrome;
• Infection at the injection site.

Precautions

Doctors take precautions when administering any medication, to reduce the risk of side effects. When administering Botox, doctors will take care not to exceed the maximum recommended dose. If an overdose is inadvertently administered, the doctor will usually monitor the person who received too much Botox for signs of systemic weakness or muscle paralysis for up to 6 weeks.

Botox will be administered in a facility with the necessary resources to manage anaphylactic shock, a rare but serious side effect of medication injections.

Doctors will also be cautious when administering Botox to certain groups of people, including those:

• Using aminoglycoside antibiotics, including:
  • Streptomycin;
  • Tobramycin;
  • Neomycin;
  • Gentamycin;
  • Netilmycin;
  • Kanamycin;
  • Amikacin;
• Using other antibiotics, including:
  • Spectinomycin;
  • Polymyxins;
  • Tetracyclines;
  • Lincomycin;
• Using any other medication that may interfere with neuromuscular transmission, including other medicines containing botulinum toxin A, the active ingredient in Botox;
• With peripheral motor neuropathies, including amyotrophic lateral sclerosis;
• Receiving frequent Botox therapy;
• Experiencing inflammation of the site to be injected;
• Experiencing excessive weakness in the target muscles;
• Who have recently been injected with any other medication containing botulinum neurotoxin. In these individuals, the doctor will usually delay administering Botox until the effects of the previous botulinum toxin therapy have resolved.
• Requiring injection to a site with structural abnormality, for example following surgery;
• Requiring injection near the thorax or lung;
• With a pre-existing cardiovascular disorder;
• With a history of seizure.

There are also a number of precautions that may be necessary, depending on the particular condition to be treated.

Blepharospasm 

When used as treatment for blepharospasm, Botox is not injected into the lower eyelid. Caution is exercised when administering Botox for blepharospasm treatment to individuals with:

• Cranial nerve VII disorders;
• Acute angle closure glaucoma or risk factors for the condition;
• Previous eye operation;
• Epithelial defect.

Strabismus

When used as treatment for strabismus, it is recommended that Botox be administered in a facility with the capacity to decompress the orbit (the cavity in which the eyeball resides), in the rare event of this cavity being penetrated with a needle during administration. The doctor may cover the eye with an eye patch following treatment, to reduce visual disturbance.

Cervical dystonia

When used as treatment for cervical dystonia, doctors will use caution when deciding which site to inject, and typically try to avoid the small neck muscle mass and injection into both sides of the sternocleidomastoid muscle. Tell your doctor if you have difficulty swallowing or breathing, as extra precautions are required to protect these functions following Botox administration.

Focal spasticity

If you receive Botox treatment for focal spasticity, you should continue with your standard treatment. Botox should be administered in addition to, rather than in place of these therapies. The doctor will examine your muscles to identify those underlying the spasticity before administering the injections. Extra precautions are required when administering the injections to children with severe cerebral palsy who also have significant neurological disability, dysphagia or a recent history of aspiration pneumonia or lung disease. Inform your doctor if your child meets these criteria.

Severe underarm sweating

When used in the treatment of hyperhidrosis of the axillae, the underlying cause of the hyperhidrosis needs to be determined to avoid treating the symptom without treating the underlying cause.

Spasmodic dysphonia

When used for the treatment of spasmodic dysphonia, treatment will only commence after the target area has been carefully examined and a definitive diagnosis is made. Botox for spasmodic dysphonia treatment will not be administered to individuals who will undergo elective surgery requiring anaesthesia, as it relaxes the vocal cords and increases the risk of aspiration during the operation.

Chronic migraine

Before receiving Botox therapy to prevent chronic migraine, you should have been diagnosed by a neurologist or pain management specialist. If you fail to respond adequately to Botox treatment after two injection sessions, you should not continue using this therapy. After three treatment cycles, the doctor will assess your response and the need for further treatment. Note that Botox is approved for the prevention of chronic migraine but is not used to treat other headaches types such as episodic migraine or tension type headache.

Cosmetic indications

For cosmetic indications, caution should be exercised when administering Botox to individuals with:

• Inflammation at the injection site;
• Facial asymmetry;
• Ptosis (drooping eyelid);
• Excessive dermatochalasis (excessive skin on the eyelids);
• Deep skin scarring;
• Thick skin; or
• Inability to substantially lessen glabellar lines by physically spreading them apart.

Use in pregnancy

Botox is a Pregnancy Category B3 medication. Botox should not be used to treat pregnant women, as safety for use in pregnancy has not been established. Animal studies have shown an increased risk of abortion, reduced foetal growth and foetal malformation. It is unclear whether Botox therapy would have the same effects in humans.

Use in breastfeeding

The safety of Botox for use by women who are breastfeeding has not been established. Doctors will use caution when deciding whether or not to administer Botox to breastfeeding women.

Children

The safety and efficacy of Botox therapy in children < 12 years old has not been established, except for the treatment of focal spasticity (although safety and efficacy has not been established for treating children < 2 years of age with this condition). For chronic migraine prevention, Botox should not be administered to children < 18 years of age.

There have been rare reports of spontaneous death and new onset or recurrent seizures following administration in children. Children are at an increased risk of death or seizures if they have any of the following conditions:

• Neuromuscular debility;
• Cardiovascular disease;
• Quadriplegia;
• Difficulty swallowing;
• History of pneumonia or lung disease;
• Feeding with a gastrointestinal tube;
• Predisposition to seizures.

Schedule

Botox is Schedule 4.¹

Common side effects

All medications have side effects, though not all individuals experience side effects when taking a medication. A doctor will assess the potential for side effects before administering any medication.

The side effects of Botox administration usually occur in the first week after administration. They are temporary, but in some cases may persist for several months. Pain or inflammation of the injection site is a common side effect of Botox use, and occurs regardless of the condition it is used to treat.

There is an extremely low risk of viral infection occurring after Botox administration (for the treatment of any condition), as the product contains an extract of human blood.

Other serious treatment-related events have been reported rarely, including:¹

• Spontaneous death following treatment;
• Anaphylactic reactions (severe allergic reactions);
• Adverse and sometimes fatal cardiovascular events, including arrhythmia and heart attack;
• Seizures;
• Respiratory distress and/or depression.

The type and frequency of other side effects vary depending on the condition being treated.

Blepharospasm

Very common side effects (side effects reported in > 10% of users):

• Ptosis (11%);
• Eye irritation or tear disorders (10%).

Uncommon side effects (side effects reported in 0.1–1% of users):

• Ectropion;
• Keratitis;
• Diplopia;
• Entropion;
• Rash;
• Eyelid swelling.

Very rare side effects (side effects reported in < 0.01% of users):

• Cardiac collapse;
• Damage to the eye’s cornea;
• Acute closed angle glaucoma.

Strabismus

Very common side effects (side effects reported in > 10% of users):

• Vertical deviation (17%);
• Partial ptosis (16%);
• Increased pressure in the eye (11%).

Common side effects (side effects reported in 1–10% of users):

• Diplopia (in patients with good vision in both eyes);
• Bleeding at the back of the eyeball.

Uncommon side effects (occurrence 0.1–1% of users):

• Headache;
• Cycloplegia (paralysis of eye muscles);
• Vertigo;
• Irritation of the eye’s cornea;
• Perforation of the sclera.

Rare side effects (side effects reported in 0.01–0.1% of users):

• Dilation of the pupil.

VIIth nerve disorders (hemifacial spasm)

In addition to those listed above, side effects include:¹

• Blurred vision;
• Facial droop;
• Dizziness;
• Tiredness.

Focal spasticity in children

Very common or common side effects (side effects reported in > 1% of users):

• Convulsions;
• Nasopharyngitis;
• Pneumonia;
• Vomiting;
• Bruising.

Common side effects (side effects reported in 1–10% of users):

• Local muscle weakness (5.4%);
• General muscle weakness (2.7%);
• Trigger finger (2.7%);
• Clumsiness (1.4%);
• Falling (1.4%);
• Hypokinesia (1.4%);
• Increased urination (1.4%);
• Joint dislocation (1.4%);
• Muscle spasms (1.4%).

Dynamic equinus foot deformity in children

Common side effects (side effects reported in 1–10% of users):

• Falling (9.3%);
• Local muscle weakness (2.3%);
• General muscle weakness (2.3%);
• Leg pain (2.3%);
• Leg cramps (1%);
• Fever (1%);
• Knee pain (1%);
• Ankle pain (1%);
• Lethargy (1%);
• Injection site pain (1%).

Uncommon side effects (occurrence < 1% of users):¹

• Urinary incontinence.

Focal spasticity in adults

Common side effects (side effects reported in 1–10% of users):

• Arm pain (1–4%);
• Hypertonia (1–4%);
• Flu-like symptoms (1%);
• Fever (1%);
• Hypertonia (in adults with focal spasticity following stroke) (4.5%);
• Asthenia (in adults with focal spasticity following stroke) (2.3%);
• Headache (in adults with focal spasticity following stroke) (2.3%);
• Hyperkinesia (in adults with focal spasticity following stroke) (2.3%);
• Accidental injury (in adults with focal spasticity following stroke) (1.2%);
• Incoordination (in adults with focal spasticity following stroke) (1.2%);
• Paraesthesia (in adults with focal spasticity following stroke) (1.2%).

Uncommon side effects (side effects reported in 0.1–1% of users):

• Hyperaesthesia;
• Joint pain;
• Weakness;
• Bursitis;
• Dermatitis;
• Headache;
• Injection site hypersensitivity;
• Malaise;
• Nausea;
• Paraesthesia;
• Postural hypotension;
• Itching.

Cervical dystonia

Very common side effects (side effects reported in > 10% of users):

• Difficulty swallowing (12.2%).

Common side effects (side effects reported in 1–10% of users):

• Neck pain (5.3%);
• Weakness (3.1%);
• Headache (1.5%);
• Pain at injection site (1.5%).

Uncommon side effects (side effects reported in 0.1–1% of users):

• Muscle weakness.

There have also been reports of dysphonia and rhinitis following Botox therapy for cervical dystonia.

Excessive underarm sweating

Common side effects (side effects reported in 1–10% of users):

• Increased sweating in places other than under the arm (4.5%);
• Injection site pain (1.7%);
• Pain (1.4%);
• Hot flushes (1%);
• Transient arm weakness (1%).

There have also been reports of body odour with this treatment.

Spasmodic dysphonia

Very common side effects (side effects reported in > 10% of users):

• Hoarse, breathy voice (47.6%);
• Difficulty swallowing (14.9%).

Common side effects (side effects reported in 1–10% of users):

• Aspiration (5.9%);
• Stridor (6.9%);
• Technical failure (8%);
• Pain (1%).

Unommon side effects (occurrence 0.1–1% of users):¹

• Gagging;
• Diplophonia (abnormal voice tone);
• Flu-like symptoms;
• Persistent cough.

Chronic migraine

Common side effects (occurrence 1–10% of users):¹

• Neck pain (8.7%);
• Headache (4.7%);
• Migraine (3.8%);
• Ptosis (drooping eyelids) (3.6%);
• Musculoskeletal stiffness (3.6%);
• Muscle weakness (3.5%);
• Injection site pain (3.3%)
• Muscle pain (3.1%);
• Musculoskeletal pain (2.6%);
• Paralysis affecting the face (2.2%);
• Muscle spasms (1.9%);
• Muscles tightness (1.3%);
• Pruritis (1%);
• Rash (1%).

Uncommon side effects (occurrence1

• Dysphagia (difficulty swallowing);
• Jaw pain;
• Skin pain.

Glabellar lines

Common side effects (side effects reported in 1–10% of users):

• Headache (9.4%);
• Blepharoptosis (3.2%);
• Pain, burning or stinging (2.5%);
• Face pain (2.2%);
• Local muscle weakness (1.7%);
• Erythema (1.7%);
• Swelling at injection site (1.5%);
• Bruising (1%);
• Skin tightness (1%);
• Paraesthesia (1%);
• Nausea (1%).

Forehead lines

Very common side effects (side effects reported in > 10% of users):

• Headache (22%);
• Eyelid swelling (20.3%);
• Bruising (10.2%);
• Eyebrow ptosis (10.2%).

Common side effects (side effects reported in 1–10% of users):

• Aching or itching forehead (5.1%);
• Nausea (3.4%);
• Tension (1.7%);
• Flu-like symptoms (1.7%).

Crow’s feet

Common side effects (side effects reported in 1–10% of users):

• Injection site bruising (8.1%);
• Temporary eyelid drooping (5%);
• Headache (3.7%);
• Flu-like symptoms (1.6%).

If you experience any of the listed side effects, or any other symptoms which appear abnormal or unusual, please tell your doctor.

References

1. Product Information: Botox. Gordon, NSW: Allergan Australia Pty Ltd; 24 March 2011.

For further information talk to your doctor.