Does Botox (onabotulinumtoxinA) cause side effects?

Botox (onabotulinumtoxinA) is an injectable neurotoxin used to treat chronic migraine headaches, axillary hyperhidrosis, upper limb spasticity, cervical dystonia, strabismus, and frown lines. 

It is a toxic chemical that blocks the ability of nerves to make muscles contract. In other words, it paralyzes muscles. 

To cause muscles to contract, nerves release a chemical, acetylcholine, where they meet muscle cells. The acetylcholine attaches to receptors on the muscle cells and causes the muscle cells to contract or shorten. 

Botox prevents the release of acetylcholine and thereby prevents contraction of the muscle cells. In order to affect the release of acetylcholine, Botox must be injected into the muscle.

Common side effects of Botox include

Serious side effects of Botox include

Patients treated for urinary incontinence may experience

Drug interactions of Botox include other agents (for example, aminoglycosides, curare) that affect neuromuscular function, which may increase the effect of Botox. Use of muscle relaxants may increase the occurrence of weakness. Use of drugs that block acetylcholine may increase some effects of Botox. 

There are no adequate studies of Botox in pregnant women. Botox has not been evaluated in nursing mothers. Consult your doctor before breastfeeding.

What are the important side effects of Botox (onabotulinumtoxinA)?

Side effects of onabotulinumtoxinA include:

Patients also complain of pain and tenderness at the injection site. Patients treated for blepharospasm may experience

  • drooping of the eyelid (ptosis),
  • inflammation of the cornea (keratitis),
  • eye dryness,
  • double vision,
  • tearing,
  • and sensitivity to light.

Those treated for urinary incontinence may experience:

Botox (onabotulinumtoxinA) side effects list for healthcare professionals

The following adverse reactions to Botox (onabotulinumtoxinA) for injection are discussed in greater detail in other sections of the labeling:

  • Spread of Toxin Effects
  • Serious Adverse Reactions with Unapproved Use
  • Hypersensitivity Reactions
  • Increased Risk of Clinically Significant Effects with Pre-Existing Neuromuscular Disorders
  • Dysphagia and Breathing Difficulties
  • Pulmonary Effects of Botox in Patients with Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity associated with a Neurologic Condition
  • Corneal Exposure and Ulceration in Patients Treated with Botox for Blepharospasm
  • Retrobulbar Hemorrhages in Patients Treated with Botox for Strabismus
  • Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity
  • Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity associated with a Neurologic Condition
  • Urinary Tract Infections in Patients with Overactive Bladder
  • Urinary Retention in Patients Treated for Bladder Dysfunction

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in cl inical practice.

Botox and Botox Cosmetic contain the same active ingredient in the same formulation, but with different labeled Indications and Usage. Therefore, adverse Reactions observed with the use of Botox Cosmetic also have the potential to be observed with the use of Botox.

In general, adverse Reactions occur within the first week following injection of Botox and, while generally transient, may have a duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema, and/or bleeding/bruising may be associated with the injection.

Symptoms associated with flu-like symptoms (e.g., nausea, fever, myalgia) have been reported after treatment. Needle-related pain and/or anxiety may result in vasovagal responses (including syncope, hypotension), which may require appropriate medical therapy.

Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of nearby muscles may also occur due to spread of toxin.

Overactive Bladder

Table 12 presents the most frequently reported adverse reactions in double-blind, placebo-controlled clinical trials for overactive bladder occurring within 12 weeks of the first Botox treatment.

Table 12: Adverse Reactions Reported by ≥2% of Botox treated Patients and More Often than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection, in Double-blind, Placebo-controlled Clinical Trials in Patients with OAB

Adverse ReactionsBotox 100 Units
(N=552)
%
Placebo
(N=542)
%
Urinary tract infection186
Dysuria97
Urinary retention60
Bacteriuria42
Residual urine volume*30
*Elevated PVR not requiring catheterization. Catheterization was required for PVR ≥350 mL regardless of symptoms, and for PVR ≥200 mL to <350 mL with symptoms (e.g., voiding difficulty).

A higher incidence of urinary tract infection was observed in patients with diabetes mellitus treated with Botox 100 Units and placebo than in patients without diabetes, as shown in Table 13.

Table 13: Proportion of Patients Experiencing Urinary Tract Infection following an Injection in Double-blind, Placebocontrolled Clinical Trials in OAB according to history of Diabetes Mellitus

Patients with DiabetesPatients without Diabetes
Botox 100 Units
(N=81)
%
Placebo
(N=69)
%
Botox 100 Units
(N=526)
%
Placebo
(N=516)
%
Urinary tract infection (UTI)31122610

The incidence of UTI increased in patients who experienced a maximum post-void residual (PVR) urine volume ≥200 mL following Botox injection compared to those with a maximum PVR <200 mL following Botox injection, 44% versus 23%, respectively.

No change was observed in the overall safety profile with repeat dosing during an open-label, uncontrolled extension trial.

Detrusor Overactivity Associated With A Neurologic Condition

Table 14 presents the most frequently reported adverse reactions in the double-blind, placebo-controlled studies within 12 weeks of injection for patients with detrusor overactivity associated with a neurologic condition treated with Botox 200 Units.

Table 14: Adverse Reactions Reported by ≥2% of Botox treated Patients and More Frequent than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection in Double-blind, Placebo-controlled Clinical Trials

Adverse ReactionsBotox 200 Units
(N=262)
%
Placebo
(N=272)
%
Urinary tract infection2417
Urinary retention173
Hematuria43

The following adverse reactions with Botox 200 Units were reported at any time following initial injection and prior to re -injection or study exit (median duration of exposure was 44 weeks):

In the Multiple Sclerosis (MS) patients enrolled in the double-blind, placebo-controlled trials, the MS exacerbation annualized rate (i.e., number of MS exacerbation events per patient-year) was 0.23 for Botox and 0.20 for placebo.

No change was observed in the overall safety profile with repeat dosing.

Table 15 presents the most frequently reported adverse reactions in a placebo-controlled, double-blind post-approval 52 week study with Botox 100 Units (Study NDO-3) conducted in MS patients with urinary incontinence due to detrusor overactivity associated with a neurologic condition.

These patients were not adequately managed with at least one anticholinergic agent and not catheterized at baseline. The table below presents the most frequently reported adverse reactions within 12 weeks of injection.

Table 15: Adverse Reactions Reported in a Post Approval Study (NDO-3) by >2% of Botox treated Patients and More Frequent than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection

Adverse ReactionsBotox 100 Unit
(N=66)
%
Placebo
(N=78)
%
Urinary tract infection266
Bacteriuria95
Urinary retention151
Dysuria51
Residual urine volume*171
* Elevated PVR not requiring catheterization. Catheterization was required for PVR ≥350 mL regardless of symptoms, and for PVR ≥200 mL to <350 mL with symptoms (e.g., voiding difficulty).

The following adverse events with Botox 100 Units were reported at any time following initial injection and prior to re-injection or study exit (median duration of exposure was 51 weeks):

  • urinary tract infections (39%),
  • bacteriuria (18%),
  • urinary retention (17%),
  • residual urine volume* (17%),
  • dysuria (9%), and
  • hematuria (5%).

No difference in the MS exacerbation annualized rate (i.e., number of MS exacerbating events per patient-year) was observed (Botox =0, placebo =0.07).

Chronic Migraine

In double-blind, placebo-controlled chronic migraine efficacy trials (Study 1 and Study 2), the discontinuation rate was 12% in the Botox treated group and 10% in the placebo-treated group.

Discontinuations due to an adverse event were 4% in the Botox group and 1% in the placebo group. The most frequent adverse events leading to discontinuation in the Botox group were neck pain, headache, worsening migraine, muscular weakness and eyelid ptosis.

The most frequently reported adverse reactions following injection of Botox for chronic migraine appear in Table 16.

Table 16: Adverse Reactions Reported by ≥2% of Botox treated Patients and More Frequent than in Placebo-treated Patients in Two Chronic Migraine Double-blind, Placebo-controlled Clinical Trials

Adverse ReactionsBotox
155 Units-195 Units
(N=687)
%
Placebo
(N=692)
%
Nervous system disorders
  Headache53
  Migraine43
  Facial paresis20
Eye disorders
  Eyelid ptosis4<1
Infections and Infestations
  Bronchitis32
Musculoskeletal and connective tissue disorders
  Neck pain93
  Musculoskeletal stiffness41
  Muscular weakness4<1
  Myalgia31
  Musculoskeletal pain31
  Muscle spasms21
General disorders and administration site conditions
  Injection site pain32
Vascular Disorders
  Hypertension21

Other adverse reactions that occurred more frequently in the Botox group compared to the placebo group at a frequency less than 1% and potentially Botox related include:

Severe worsening of migraine requiring hospitalization occurred in approximately 1% of Botox treated patients in Study 1 and Study 2, usually within the first week after treatment, compared to 0.3% of placebo-treated patients.

Adult Upper Limb Spasticity

The most frequently reported adverse reactions following injection of Botox for adult upper limb spasticity appear in Table 17.

Table 17: Adverse Reactions Reported by ≥2% of Botox treated Patients and More Frequent than in Placebo-treated Patients in Adult Upper Limb Spasticity Double-blind, Placebo-controlled Clinical Trials

Adverse ReactionsBotox
251 Units - 360 Units
(N=115)
%
Botox
150 Units - 250 Units
(N=188)
%
Botox
<150 Units
(N=54)
%
Placebo
(N=182)
%
Gastrointestinal disorder
  Nausea3221
General disorders and administration site conditions
  Fatigue3220
Infections and infestations
  Bronchitis3201
Musculoskeletal and connective tissue disorders
  Pain in extremity6594
  Muscular weakness0421

Twenty two adult patients, enrolled in double-blind placebo controlled studies, received 400 Units or higher of Botox for treatment of upper limb spasticity. In addition, 44 adults received 400 Units of Botox or higher for four consecutive treatments over approximately one year for treatment of upper limb spasticity.

The type and frequency of adverse reactions observed in patients treated with 400 Units of Botox were similar to those reported in patients treated for upper limb spasticity with 360 Units of Botox.

Adult Lower Limb Spasticity

The most frequently reported adverse reactions following injection of Botox for adult lower limb spasticity appear in Table 18. Two hundred thirty one patients enrolled in a double-blind placebo-controlled study (Study 6) received 300 Units to 400 Units of Botox, and were compared with 233 patients who received placebo. Patients were followed for an average of 91 days after injection.

Table 18: Adverse Reactions Reported by ≥2% of Botox treated Patients and More Frequent than in Placebo-treated Patients in Adult Lower Limb Spasticity Double-blind, Placebo-controlled Clinical Trial (Study 6)

Adverse ReactionsBotox
(N=231)
%
Placebo
(N=233)
%
Musculoskeletal and connective tissue disorders
  Arthralgia31
  Back pain32
  Myalgia21
Infections and infestations
  Upper respiratory tract infection21
General disorders and administration site conditions
  Injection site pain21

Pediatric Upper Limb Spasticity

The most frequently reported adverse reactions following injection of Botox in pediatric patients 2 to 17 years of age with upper limb spasticity appear in Table 19.

In a double-blind, placebo-controlled trial (Study 1), 78 patients were treated with 3 Units/kg of Botox, and 77 patients received 6 Units/kg to a maximum dose of 200 Units of Botox, and were compared to 79 patients who received placebo. Patients were followed for an average of 91 days after injection.

Table 19: Adverse Reactions Reported by ≥2% of Botox 6 Units/kg treated Patients and More Frequent than in Placebotreated Patients in Pediatric Upper Limb Spasticity Double-blind, Placebo-controlled Clinical Trial (Study 1)

Adverse ReactionsBotox
6 Units/kg
(N=77)
%
Botox
3 Units/kg
(N=78)
%
Placebo
(N=79)
%
Infections and infestations
  Upper respiratory tract infection*17109
General disorders and administration site conditions
  Injection site pain431
Gastrointestinal disorders
  Nausea400
  Constipation301
Respiratory, thoracic and mediastinal disorders
  Rhinorrhea401
  Nasal congestion301
Nervous system disorders
  Seizure**510
*Includes upper respiratory tract infection and viral upper respiratory tract infection
**Includes seizure and partial seizure

Cervical Dystonia

In cervical dystonia patients evaluated for safety in double-blind and open-label studies following injection of Botox, the most frequently reported adverse reactions were

Other events reported in 2-10% of patients in any one study in decreasing order of incidence include:

Stiffness, numbness, diplopia, ptosis, and dyspnea have been reported.

Dysphagia and symptomatic general weakness may be attributable to an extension of the pharmacology of Botox resulting from the spread of the toxin outside the injected muscles.

The most common severe adverse reaction associated with the use of Botox injection in patients with cervical dystonia is dysphagia with about 20% of these cases also reporting dyspnea. Most dysphagia is reported as mild or moderate in severity. However, it may be associated with more severe signs and symptoms.

Additionally, reports in the literature include a case of a female patient who developed brachial plexopathy two days after injection of 120 Units of Botox for the treatment of cervical dystonia, and reports of dysphonia in patients who have been treated for cervical dystonia.

Primary Axillary Hyperhidrosis

The most frequently reported adverse reactions (3-10% of adult patients) following injection of Botox in double-blind studies included

The data reflect 346 patients exposed to Botox 50 Units and 110 patients exposed to Botox 75 Units in each axilla.

Blepharospasm

In a study of blepharospasm patients who received an average dose per eye of 33 Units (injected at 3 to 5 sites) of the currently manufactured Botox, the most frequently reported adverse reactions were

  • ptosis (21%),
  • superficial punctate keratitis (6%), and
  • eye dryness (6%).

Other events reported in prior clinical studies in decreasing order of incidence include:

  • irritation,
  • tearing,
  • lagophthalmos,
  • photophobia,
  • ectropion,
  • keratitis,
  • diplopia,
  • entropion,
  • diffuse skin rash, and
  • local swelling of the eyelid skin lasting for several days following eyelid injection.

In two cases of VII nerve disorder, reduced blinking from Botox injection of the orbicularis muscle led to serious corneal exposure, persistent epithelial defect, corneal ulceration and a case of corneal perforation. Focal facial paralysis, syncope, and exacerbation of myasthenia gravis have also been reported after treatment of blepharospasm.

Strabismus

Extraocular muscles adjacent to the injection site can be affected, causing vertical deviation, especially with higher doses of Botox. The incidence rates of these adverse effects in 2058 adults who received a total of 3650 injections for horizontal strabismus was 17%.

The incidence of ptosis has been reported to be dependent on the location of the injected muscles, 1% after infer ior rectus injections, 16% after horizontal rectus injections and 38% after superior rectus injections.

In a series of 5587 injections, retrobulbar hemorrhage occurred in 0.3% of cases.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

For these reasons, comparison of the incidence of antibodies to onabotulinumtoxinA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In a long-term, open-label study evaluating 326 cervical dystonia patients treated for an average of 9 treatment sessions with the current formulation of Botox, 4 (1.2%) patients had positive antibody tests. All 4 of these patients responded to Botox therapy at the time of the positive antibody test. However, 3 of these patients developed clinical resistance after subsequent treatment, while the fourth patient continued to respond to Botox therapy for the remainder of the study.

One patient among the 445 hyperhidrosis patients (0.2%), two patients among the 380 adult upper limb spasticity patients (0.5 %), and no patients among 406 migraine patients with analyzed specimens developed the presence of neutralizing antibodies.

In overactive bladder patients with analyzed specimens from the two phase 3 studies and the open-label extension study, neutralizing antibodies developed in 0 of 954 patients (0.0%) while receiving Botox 100 Unit doses and 3 of 260 patients (1.2%) after subsequently receiving at least one 150 Unit dose. Response to subsequent Botox treatment was not different following seroconversion in these three patients.

In detrusor overactivity associated with neurologic condition patients with analyzed specimens in the drug development program (including the open-label extension study), neutralizing antibodies developed in 3 of 300 patients (1.0%) after receiving only Botox 200 Unit doses and 5 of 258 patients (1.9%) after receiving at least one 300 Unit dose.

Following development of neutralizing antibodies in these 8 patients, 4 continued to experience clinical benefit, 2 did not experience clinical benefit, and the effect on the response to Botox in the remaining 2 patients is not known.

The data reflect the patients whose test results were considered positive for neutralizing activity to Botox in a mouse prote ction assay or negative based on a screening ELISA assay or mouse protection assay.

Formation of neutralizing antibodies to botulinum toxin type A may reduce the effectiveness of Botox treatment by inactivating the biological activity of the toxin. The critical factors for neutralizing antibody formation have not been well characterized.

The results from some studies suggest that Botox injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between injections.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Botox. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include:

There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or anaphylaxis, after treatment with botulinum toxin.

There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including cardiovascular disease. The exact relationship of these events to the botulinum toxin injection has not been established.

New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The exact relationship of these events to the botulinum toxin injection has not been established.

What drugs interact with Botox (onabotulinumtoxinA)?

Aminoglycosides And Other Agents Interfering With Neuromuscular Transmission

Co-administration of Botox and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare -like compounds) should only be performed with caution as the effect of the toxin may be potentiated.

Anticholinergic Drugs

Use of anticholinergic drugs after administration of Botox may potentiate systemic anticholinergic effects.

Other Botulinum Neurotoxin Products

The effect of administering different botulinum neurotoxin products at the same time or within several months of each other i s unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.

Muscle Relaxants

Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of Botox.

Summary

Botox (onabotulinumtoxinA) is an injectable neurotoxin used to treat chronic migraine headaches, axillary hyperhidrosis, upper limb spasticity, cervical dystonia, strabismus, and frown lines. Common side effects of Botox include allergic reactions, rash, itching, headache, neck pain, difficulty swallowing, shortness of breath, nausea, weakness, dry mouth, and pain and tenderness at the injection site. There are no adequate studies of Botox in pregnant women. Botox has not been evaluated in nursing mothers.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 8/18/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.