Botox Injections and Side Effects

Botulinum toxin type A (Botox) is a neurotoxin derived from Clostridium botulinum and is widely used in dermatology and aesthetic medicine for both cosmetic and therapeutic purposes. In dermatologic practice, its most common indication is the temporary reduction of dynamic facial wrinkles, particularly glabellar lines, horizontal forehead lines, and crow’s feet. Beyond cosmetic use, botulinum toxin has been approved for several medical dermatologic conditions, including primary axillary hyperhidrosis, rosacea-associated flushing, and refractory pruritus.

The mechanism of action involves inhibition of acetylcholine release at the neuromuscular junction, leading to temporary muscle paralysis. In cosmetic use, this reduces muscle activity that contributes to wrinkle formation. In hyperhidrosis, botulinum toxin blocks cholinergic transmission to eccrine sweat glands, thereby reducing sweat production. The effects typically begin within 3-7 days of injection, peak at 1-2 weeks, and last approximately 3-4 months, although duration may vary based on the dose, site of injection, and patient-specific factors.

Adverse effects are generally mild and self-limited, with the most common being bruising, headache, pain at the injection site, and ptosis (eyelid drooping) when injections diffuse into adjacent muscles. In rare cases, systemic effects such as dysphagia, muscle weakness, or allergic reactions can occur, especially with high doses or off-label use. Proper injection technique and anatomic knowledge are essential to minimizing complications.

From a pharmacy standpoint, although pharmacists do not administer botulinum toxin in most settings, they may be involved in product selection, storage and reconstitution, and patient counseling. Botulinum toxin products must be stored under refrigeration and reconstituted with preservative-free saline. Pharmacists may also assist in differentiating between available formulations (Botox, Dysport, Xeomin, Jeuveau), which are not interchangeable due to differences in unit potency, protein complexes, and diffusion characteristics.

Pharmacists also play a role in educating patients on realistic expectations, onset and duration of action, signs of adverse effects, and appropriate intervals between treatments. In specialty or compounding settings, pharmacists may counsel on adjunctive skincare or treatment for coexisting dermatologic concerns (combining botulinum toxin with topical retinoids or fillers in anti-aging regimens).

As minimally invasive aesthetic procedures continue to expand, botulinum toxin remains a cornerstone in cosmetic dermatology and a therapeutic option for select skin conditions. Pharmacists are uniquely positioned to support safe, effective use through interdisciplinary collaboration, education, and quality assurance in handling.

References:

Carruthers A, Carruthers J. Botulinum toxin type A: history and current cosmetic use in the upper face. Semin Cutan Med Surg. 2001;20(2):71–84. doi:10.1053/scms.2001.23250

Naumann M, So Y, Argoff CE, Childers MK, Dykstra DD, Gronseth GS. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review). Neurology. 2008;70(19):1707–1714. doi:10.1212/01.wnl.0000311391.87642.e7

Glogau RG. Botox for hyperhidrosis and other dermatologic uses. Dermatol Clin. 2004;22(2):177–185. doi:10.1016/S0733-8635(03)00111-0

Wollina U. Botulinum toxin: current use in dermatology. Skin Therapy Lett. 2005;10(5):1–5. PMID:16130840

Sadick NS. Aesthetic applications of botulinum toxin. Dermatol Clin. 2004;22(2):131–138. doi:10.1016/S0733-8635(03)00107-9

Since the FDA first approved BOTOX (onabotulinumtoxinA) in 1989 for the treatment of two rare eye muscle disorders—blepharospasm and strabismus in adults—its therapeutic applications have expanded significantly. OnabotulinumtoxinA is now FDA-approved for 12 therapeutic indications, including chronic migraine, overactive bladder, urinary incontinence due to a neurologic condition in adults, cervical dystonia, adult and pediatric spasticity, severe underarm sweating (axillary hyperhidrosis), and pediatric detrusor overactivity associated with a neurologic condition.

On April 15, 2002, the FDA approved BOTOX® for cosmetic use as a temporary treatment for moderate to severe frown lines in adults. To distinguish it from its therapeutic uses, it was marketed as BOTOX® Cosmetic. This prescription medicine is FDA-approved for three specific areas: moderate to severe forehead lines, lateral canthal lines, and glabellar lines. It was the first treatment of its kind and remains the only FDA-approved product for improving the appearance of moderate to severe frown lines, crow’s feet, and forehead lines in adults.

The clinical effects of botulinum toxin typically begin to appear within one to three days, peak in one to four weeks, and gradually diminish after three to four months. However, the duration of the response varies based on the injection site, dose, and specific formulation used. Some patients, especially those who have had repeated injections in the same area, may experience benefits for six months or longer, potentially due to muscle atrophy.

When patients are carefully selected, and proper dosing and injection techniques are utilized, the use of botulinum toxin for cosmetic purposes is generally safe. Side effects are usually mild and temporary, including swelling or bruising at the injection site, mild headaches, or flu-like symptoms. Occasionally, unintended muscle impairment may occur, often due to poor injection technique or inappropriate patient selection. Thus, a conservative approach to dosing is advisable to minimize adverse effects.

A review of available data underscores the impressive safety record of botulinum toxin. A 2004 systematic review and meta-analysis of randomized trials involving 1,425 patients reported no serious adverse effects from onabotulinumtoxinA used for medical or cosmetic purposes. Between 1989 and 2003, only 36 serious adverse effects associated with cosmetic use were reported to the FDA. These included injection site reactions, headaches, focal facial paralysis, muscle weakness, flu-like symptoms, dysphagia, respiratory compromise, cardiac arrhythmia, seizures, ocular abnormalities, and allergic reactions. Notably, 13 of these cases involved patients with underlying medical conditions that may have contributed to the adverse event.

Despite the low risk of serious adverse effects with cosmetic use, there have been reports of severe side effects such as aspiration, dysphagia, pneumonia, anaphylaxis, botulism, and death. Consequently, in 2009, the FDA mandated boxed warnings on botulinum toxin product labels and required a Risk Evaluation and Mitigation Strategy for all such products.

Due to the temporary nature of botulinum toxin’s effects, patients need ongoing treatments to maintain their results. The safety of repeated treatments was assessed in a retrospective study involving over 4,000 treatments in 945 patients for upper face lines, with each patient receiving at least three consecutive treatment cycles. Only mild to moderate adverse effects, such as bruising and ptosis, were observed, with a decrease in side effects noted over repeated injections. Similar findings have been reported in studies of botulinum toxin type A for medical uses, and repeat injections with abobotulinumtoxinA have also shown good tolerance in large open-label studies.

Overall, while BOTOX has a well-established safety profile, ongoing monitoring and careful patient selection remain crucial to minimize the risk of adverse effects and ensure the best therapeutic and cosmetic outcomes.

BOTOX® Cosmetic (Boe-tox) (onabotulinumtoxinA) for Injection. (2021, February). U.S. Food and Drug Administration. Retrieved from https://www.rxabbvie.com/pdf/botox_medguide.pdf

BOTOX® Cosmetic (Boe-tox) (onabotulinumtoxinA) for Injection. (2021, February). U.S. Food and Drug Administration. Retrieved from https://www.rxabbvie.com/pdf/botox_medguide.pdf

Botox, a popular cosmetic treatment, is widely recognized for its ability to reduce the appearance of facial wrinkles and fine lines. Derived from the bacterium Clostridium botulinum, Botox works by temporarily paralyzing specific muscles, leading to a smoother and more youthful appearance.

One of the main advantages of Botox is its effectiveness in treating dynamic wrinkles, which are caused by repetitive muscle movements. Common areas for Allergan Botox treatment include forehead lines, crow’s feet around the eyes, and frown lines between the eyebrows. The procedure is quick, minimally invasive, and typically involves little to no downtime, making it a convenient option for many people.

Beyond its cosmetic uses, Botox has several medical applications. It can help alleviate chronic migraines, reduce excessive sweating (hyperhidrosis), manage muscle spasms, and treat certain bladder and bowel disorders. These therapeutic benefits have expanded its use in the medical field, providing relief for various conditions.

Botulinum toxin, produced by the bacterium Clostridium botulinum, is a highly potent neurotoxin that has been utilized by clinicians since the late 1970s. Clostridium botulinum is a spore-forming, gram-positive, anaerobic bacterium. Botulinum neurotoxins consist of seven distinct stereotypes, labeled A through G, four of which are efficacious for practical use. Globally, all four stereotypes are approved for the treatment of spasmodic spasmodic torticollis, a condition characterized by abnormal head movements. Additionally, there are three different forms of Stereotype A, all of which are approved for focal dystonia, characterized by eyelid twitching or closure. 

Botulinum toxin, also more commonly known as Botox, has gained FDA approval for a number of indications. The only chronic condition that Botox is currently FDA-indicated for is in the treatment of migraines. Specifically, botox is recommended for the prophylaxis of migraines in adult patients who experience chronic migraine, defined as migraines occurring at least 15 days per month, each episode lasting at least 4 hours. Other FDA-approved indications for botulinum toxin also include: 

• Primary axillary hyperhidrosis: indicated in patients with severe hyperhidrosis when topical agents have been insufficient. Notably, its use has not been established as safe or effective in patients less than 18 years of age. 

• Adult bladder dysfunction: indicated in adults with inadequate response or intolerance to anticholinergic medications, used in the management of overactive bladders in patients with urgency, frequency and urinary incontinence. ‘

• Muscle stiffness/rigidity: indicated in patients at least 2 years of age for the treatment of spasticity

Botulinum toxin works by acting as a powerful zinc neurotoxin that attaches to receptors outside cells on cholinergic nerve endings, where it breaks down one of the three soluble N-ethylmaleimide-sensitive factor attachment receptor proteins (SNARE). This process temporarily hinders the release of acetylcholine from intracellular presynaptic vesicles, resulting in a brief reduction in neurotransmitter release at the neuromuscular junction. SNARE proteins also play a known role in neurons that release glutamate and substance R, facilitating the release of bradykinin, prostaglandins, histamine and serotonin, all of which are inflammatory agents. The suppression of these agents is also a possible explanation for its potential efficacy in treating chronic pain disorders, migraines and neuralgias. Botulinum toxin has a prolonged period of effectiveness following administration; it typically requires about two weeks to fully manifest its efficacy and lasts three to five months in cosmetic applications. However, its therapeutic applications targeting autonomic neurons for conditions like hyperhidrosis or overactive bladder yield a notably longer duration of acting, typically lasting between six to nine months. 

There are currently 4 FDA-approved preparations for botulinum toxin that are available on the market:

• OnabotulinumtoxinA 

• AbobotulinumtoxinA

• IncobotulinumtoxinA 

• RimabotulinumtoxinB 

The pharmaceutical formulations for all four products are packaged and distributed in powder form. Dilution of the powdered pharmaceutical form of botulinum toxin should be approached with caution, especially if a more substantial dilution with saline is intended. Such dilution may lead to unintended diffusion to adjacent regions, resulting in less-than-ideal outcomes; it may also trigger undesired adverse effects such as eyelid ptosis (drooping of the upper eyelid). 

Resources: 

Padda IS, Tadi P. Botulinum Toxin. [Updated 2023 Nov 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557387/

Botox injections. Mayo Clinic. March 10, 2023. Accessed May 3, 2024. https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658.

Botox Injections and Their Side Effects

BOTOX is the trade name for onabotulinumtoxinA for injection. The routes of administration are intramuscular, intradetrusor, or intradermal use. The mechanism of action is to inhibit acetylcholine release and a neuromuscular blocking agent (Botox Package Insert). Botox is a chemically modified derivative of the botulinum toxin that is produced by the bacteria clostridium botulinum, which is a potent neurotoxin. Botulinum toxin is present in 7 different serotypes, but type A is most widely used, especially in the aesthetic and dermatology industries (Nigam PK). For therapeutic use, Botox is produced and harvested via chemical reactions into a sterile lyophilized form that is suitable for injection (Padda, IS).

The approved FDA indications for Botox include treatment of overactive bladder, urinary incontinence, treatment of neurogenic detrusor overactivity, treatment of bladder, migraine and headache prophylaxis, treatment of cervical dystonia, and treatment of severe axillary hyperhidrosis (Botox Package Insert).  In contrast to its approved indications for use, Botox is primarily known for its cosmetic benefits in reducing wrinkles and frown lines, which is not an FDA- approved use for the product (Satriyasa BK).  

                  Despite its popularity for minimizing the appearance and development of wrinkles, Botox does have side effects associated with its use. There is a Black Box Warning regarding the risk of distant spread of toxin effect. This means that drug can spread from the injection site and can produce symptoms of botulinum toxicity in other parts of the body within hours to weeks after receiving the product. Symptoms can be life threatening and fatal. Side effects can include bleeding, swelling, redness, and pain at the injection site. Other side effects include malaise, flu- like symptoms, and nausea. Botox can also cause trouble breathing and trouble swallowing, which can be fatal (Botox Package Insert).

To avoid potential complications, patients should be adequately screened for any complications or conditions that may predispose them to severe reactions, including allergies or injecting into open wounds (Botox Package Insert). Additionally, only licensed, and trained individuals should inject the product for cosmetic or therapeutic purposes. The minimum therapeutic concentration should be used, with appropriate doses being injected at least 1 centimeter apart (Satriyasa BK).

Citations:

Botox [Package Insert]. North Chicago, Illinois: Allergan Aesthetics (Abbvie), Revised 11/2023

Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8-14. doi:10.4103/0019-5154.60343

Padda IS, Tadi P. Botulinum Toxin. [Updated 2023 Nov 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557387/

Satriyasa BK. Botulinum toxin (Botox) A for reducing the appearance of facial wrinkles: a literature review of clinical use and pharmacological aspect. Clin Cosmet Investig Dermatol. 2019;12:223-228. Published 2019 Apr 10. doi:10.2147/CCID.S202919

Many are familiar with botox injections as a popular cosmetic treatment to help treat facial wrinkles. However, Botox is also used for various medical conditions such as migraines, muscle spasms, and hyperhidrosis. Botox, short for botulinum toxin, works by blocking nerve signals in the muscles where it is injected, which causes temporary muscle paralysis. The toxin is derived from the Clostridium botulinum bacterium and works by inhibiting the release of acetylcholine at the neuromuscular junction, effectively blocking muscle contraction. This paralysis smooths out wrinkles and relieves muscle-related symptoms. Botulinum toxin type A is primarily used for cosmetic purposes, while type B is used for conditions such as dystonia. FDA-approved botulinum toxin type A products include onabotulinumtoxin A (Botox), abobotulinumtoxin A (Dysport), and incobotulinumtoxin A (Xeomin). As pharmacy professionals, it is important to understand Botox and its potential side effects to provide safe and effective care to patients.

A common uses of Botox is in cosmetic procedures to reduce the appearance of wrinkles. When used for medical purposes, Botox is usually covered by insurance. However, it is important to note that Botox is a prescription medication and should only be used under the supervision of a qualified healthcare provider. While Botox is considered safe when administered correctly, it can cause side effects in some people. Common injection reactions include anxiety, erythema, headache, infection, or pain, with bruising and redness being more common. NSAIDs can be used to treat headaches resulting from the procedure. Side effects of botulinum toxin include allergic reactions, spreading from the injection site, eyebrow ptosis, or facial asymmetry. More serious side effects of Botox can occur if the toxin spreads beyond the injection site. This can cause muscle weakness, vision problems, difficulty speaking or swallowing, and breathing difficulties to which medical attention is needed. As pharmacy professionals, it is important to educate patients about the potential side effects of Botox and how to recognize them. Patients should also be informed about the proper administration and storage of Botox to ensure its effectiveness and safety.

References:

Botox Injections. Mayo Clinic, Mayo Foundation for Medical Education and Research www.mayoclinic.org/tests-procedures/botox/about/pac-20384658.

Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin 2004; 20:981.

Botox, otherwise known as onabotulinumtoxinA is an FDA-approved aesthetic and therapeutic product. It is a potent neurotoxin produced by the bacterium Clostridium botulinum which inhibits the release of the neurotransmitter acetylcholine from axon endings resulting in temporary muscle relaxation and paralysis. An acetylcholine release inhibitor and a neuromuscular block agent, Botox is approved for overactive bladder (OAB), chronic migraine, adult spasticity, and severe axillary hyperhidrosis. Off-label indications include post-stroke pain, diabetic neuropathy, trigeminal neuralgia, spinal cord injury, and bladder pain. Effects on the injection site last for a few months before nerve endings regenerate, allowing muscle function to gradually return.

Since first approved in 1989, Botox has grown to a current estimated market value of 8 billion US dollars. It is projected to grow to 13 billion US dollars by 2030. Although, a successful product in the cosmetic industry, as society says, ‘beauty comes with pain’. Common side effects include pain at the injection site, headache, itching, swelling, and a rash. More serious side effects include droopy eyes, drooling, blurred vision, and difficulty breathing. Prolonged usage can have long-term effects such as loss of muscle function. This can be seen as a benefit in some cases due to the inability to now develop wrinkles. There have been reports of death associated with dysphagia, pneumonia, and/or anaphylaxis after receiving botulinum toxin. In fact, upon post-marketing surveillance, patients were reported to have cardiovascular side effects including arrhythmias and myocardial infarctions. However, no research has been conducted to determine a causal relation between cardiovascular events and Botox use. 

Excessive doses of Botox produce a neuromuscular weakness which may require respiratory support due to the paralysis of respiratory muscles. In the event of an overdose, it is essential to monitor the patient's symptoms of unwarranted muscle weakness and/or paralysis. Due to the chemical nature of Botox, symptoms of overdose are unlikely to be seen immediately upon injection and may be seen weeks or even months after injection. In the event of an overdose, an antitoxin against botulinum toxin is available from the CDC. However, the antitoxin will not prove to be useful in reversing any toxicity that is noticed at the time of antitoxin administration.

Botox is a revolutionary product that aids in treating conditions that may not be adequately treated with first, second, and even third-line medications. As health care practitioners and educators, we must educate the patients on the risks versus the benefits of Botox usage. Studies are still being conducted to expand treatment indications and continue observing the safety and efficacy profile of Botox.

References

https://www.botox.com/

https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658

https://my.clevelandclinic.org/health/treatments/8312-botulinum-toxin-injections

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489637/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828686/

Botox for Hyperhidrosis

Botox, short for Botulinum toxin, is a neurotoxic protein produced by the bacterium Clostridium botulinum. Despite being a potent toxin, it has various medical and cosmetic uses. The toxin works by blocking nerve signals in the muscles where it is injected, leading to temporary muscle paralysis. This property makes it useful for treating certain medical conditions and for cosmetic procedures.

In the medical field, Botox is used to treat conditions such as muscle spasms, excessive sweating (hyperhidrosis), and migraines. In the cosmetic industry, it is commonly used for facial rejuvenation to reduce the appearance of wrinkles and fine lines. By paralyzing or weakening specific facial muscles, Botox can smooth out wrinkles and create a more youthful appearance.

Currently, there are multiple forms of botulinum toxin-A on the market. The botulinum toxin we know of most famously is the brand name Botox, onabotulinum toxin-a. There is also Dysport (abobotulinum toxin-A) and Xeomin (incobotulinum toxin A). Most studies have been done on the brand name Botox, which has been FDA-approved since 1989. In 2004, the FDA approved Botox for the treatment of severe hyperhidrosis. I will delve further below into the use of Botox for hyperhidrosis. 

OnabotulinumtoxinA is a naturally purified protein known for its capacity to temporarily hinder the release of the chemical responsible for activating the body's sweat glands. Through the interruption of this chemical messenger, botulinum toxin effectively halts sweating in the injected area. Botox injections are administered at a very shallow depth, ensuring that the medication is placed just beneath the skin's surface, where it retains its effectiveness.

The injections utilize the smallest needle size possible and only penetrate the outermost layer of the skin. When applying an over-the-counter anesthetic cream, such as 4 or 5 percent Recticare, injections in the underarms become almost painless. However, injecting into the palms is more challenging due to their thicker skin, resulting in increased discomfort. Following hand treatment, certain individuals may experience a temporary reduction in grip strength, typically lasting an average of two to three weeks.

Scientific research indicates that the use of onabotulinumtoxinA in treating excessive sweating in areas such as the armpits, hands, feet, craniofacial region, and smaller body areas (like under the breasts) is both safe and effective. When employed for underarm hyperhidrosis, Botox has demonstrated an 82-87% reduction in sweating. Noticeable results typically emerge within 2 to 4 days post-treatment, with full effects usually observed within 2 weeks. The dryness effect commonly persists for 4 to 12 months, although certain studies suggest it may extend up to 14 months. Numerous published research studies present additional statistics supporting the safety and efficacy of repeated Botox treatments for hyperhidrosis, consistently leading to significant and enduring improvements in patients' symptoms, daily functioning, and quality of life.

The primary drawback of Botox treatment lies in its cost, given the considerable expense of the medication. However, insurance may provide coverage following precertification and typically reimburses at a predetermined rate.

Botox for hyperhidrosis is a game changer for patient’s quality of life and should be considered the treatment of choice for patients who can afford it.

References:

1. https://www.bcm.edu/healthcare/specialties/dermatology/excessive-sweating-options/botox-for-excessive-sweating#:~:text=Botox%20injections%20have%20been%20FDA,special%20care%20is%20needed%20afterward.

2. https://www.sweathelp.org/hyperhidrosis-treatments/botox.html

3. Grunfeld, A., Murray, C. A., & Solish, N. (2009). Botulinum toxin for hyperhidrosis: a review. American journal of clinical dermatology, 10(2), 87–102. https://doi.org/10.2165/00128071-200910020-00002

Botulinum toxin, better known as Botox. This is one of the most poisonous biological substances known. Botox is a neurotoxin produced by bacterium Clostridium botulinum and elaborates antigenically distinguishable exotoxins. Botox plays a very important role in the management a wide variety of medical conditions such as, strabismus, chronic migraine, spastic disorder and dystonia. Botox, however, is most known for its use in cosmetic and beauty enhancements. Botox is used to correct lines, creases and wrinkling all over the face, chin and neck. Botox in undeniably an extremely powerful medication, but the side effects are something that must be considered to really justify its benefits.

The mechanism of Botox interferes with neural transmission by blocking the release of acetylcholine, the principal transmitter at the neuromuscular junction, causing muscle paralysis. Botulinum toxin initiates weakness of the striated muscles by stopping transmission of alpha motor neurons at the neuromuscular junction. Hence why it is used to treat conditions with muscular overactivity. The toxin also inhibits release of acetylcholine in all parasympathetic and cholinergic postganglionic sympathetic neurons. For reason, this has caused interest in using Botox ins treatments like overactive smooth muscles of abnormal activity of glands. Botox takes about 24 to 72 hours to take effects, due to the time necessary to disrupt the synaptosomal process. The effects of Botox tend to peak at about 10 days after injection, however, the effects of Botox usually last about three months.

Botox injections are usually well tolerated, and even more so when used for cosmetic uses versus therapeutic uses. Common side effects include, injection pain site, local edema, erythema, transient numbness, headache and nausea. Other side effects include, flu like symptoms.

One of the most rare, but dangerous side effects of Botox is temporary unwanted paralysis of nearby musculature caused by the action of the toxin. This side effect usually subsides in several months and ins some patients a few weeks all depending on the site, strength and muscle weakness. Practices that are done to avoid this side effects is patients being told to remain in an upright positions for the next three to four hours following injection and avoid manual manipulation of the area injected. Active contraction of th4 muscles under treatment may increase the uptake of toxin and decrease its diffusion. Botox being so powerful, it is important to have precise handling and understanding of the functional anatomy of the mimetic muscles to correctly used Botox in clinical practices.

Botox may also cause extra side effects to patients when they are taking certain medications, drug-drug interactions. This includes the use of NSAIDS and Botox together may cause bruising temporarily when Botox is first injected. It is usually recommended that patients stop taking these products two weeks before the procedure. Drugs that are contraindicated when taking Botox include aminoglycosides, due to the possibility of enhancing the effects of Botox. On the other hand, drugs such as quinine, chloroquine and hydroxychloroquine are contraindicated while on Botox as it may reduce the effects of it.

Botox is an extremely powerful drug that has greatly empowered the drug and cosmetic industry. It is not a drug to be taken lightly however, as it poses a list of potential side effects that can be extremely harmful or unwarranted.

References:

Nigam, P K, and Anjana Nigam. “Botulinum toxin.” Indian journal of dermatology vol. 55,1 (2010): 8-14. doi:10.4103/0019-5154.60343

Mayo Foundation for Medical Education and Research. (2023, March 10). Botox injections. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658#:~:text=Botox%20injections%20are%20shots%20that,lazy%20eye%20and%20other%20conditions.

Botox, or botulinumtoxinA (BoNT-A) is a neurotoxin mainly used for reducing glabellar lines, or frown lines, which are vertical lines that appear between the eyebrows. It is also widely used as an off label indication for improving the appearance of wrinkles and fine lines in other areas of the face. Botox is administered as injection shots and prevents a muscle from moving for a limited time by blocking certain chemical signals from nerves that cause muscles to contract. There are currently three FDA approved commercial BoNT-A formulations which includes AbobotulinumtoxinA (ABO), incobotulinumtoxinA (INCO), and onabotulinumtoxinA (ONA). These are also extensively used as off-label for a multitude of other purposes.

The mechanism of action of BoNT-A upon being injected into a muscle entails BoNT-A traveling to the neuromuscular junction, and binding first to a high-affinity presynaptic receptor. This allows entry into the presynaptic nerve terminal through receptor-mediated endocytosis into an endosome. The heavy and light chains dissociate by disulfide bond breakage, and the zinc-dependent endoprotease, which is the light chain, is released into the nerve ending. In the nerve terminus, this cleaves synaptosomal-associated protein 25 or SNAP-25, which plays a key role in acetylcholine release during nerve stimulation. This cleavage blocks the release of acetylcholine into the synaptic cleft, preventing the stimulus from reaching the muscle until the function of the neuromuscular junction is restored in three to six months.

Some medical conditions that can be treated with Botox injections include neck spasms, cerebral palsy and other conditions of the nervous system, lazy eye, hyperhidrosis, migraines, and bladder problems. Neck spasms are a painful condition in which the neck muscles involuntarily tighten, leading to the head twisting or turning into an uncomfortable position. This condition is also referred to as cervical dystonia. Cerebral palsy and some other conditions of the nervous system cause the limbs to pull in toward the center of the body and muscle spasms also can cause eye twitching. For lazy eye, there is an imbalance in the muscles used for moving the eye which is why the condition can also be called crossed eyes or misaligned eyes. Botox is used for migraines when individuals have been suffering from one for 15 or more days in a month. Botox shots can also help reduce urinary incontinence caused by an overactive bladder.

Implications for BoNT-A in wound healing, facial cutaneous scarring, and cleft lip repair has been studied. The application of tension on wound edges during the healing process is a crucial factor influencing wound healing and the ultimate cosmetic result of cutaneous scars. Continuous tension, caused by the superficial attachments of facial muscles, can lead to complications in the healing of skin wounds. There have been reports of the benefits of the use of botulinum toxin type A in the management of various facial wounds including cleft lip surgery.

Taking advantage of the temporary paralyzing effects of botulinum toxin presents an intriguing approach to diminish the cycles of micro-trauma during the initial stages of wound healing, aiming to enhance the overall quality of the scar. It has proven its safety and efficacy through its chemo-denervative function. By denervating the underlying muscles, it diminishes tension on the wound edges, leading to an enhancement in the quality of the resultant scar. The impact of botulinum toxin is evident not only on the cellular and molecular levels but also on the neurogenic pathways.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074896/

https://academic.oup.com/asj/article/37/suppl_1/S45/3098966

https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658

https://oregonmedicalresearch.com/patients/conditions-we-study/frown-lines/#:~:text=Frown%20lines%2C%20or%20glabellar%20lines,action%20can%20cause%20permanent%20wrinkles.

General Overview of Botox

Botulinum toxin, a neurotoxin derived from Clostridium botulinum, finds extensive use in both therapeutic and cosmetic applications. It is used for managing various conditions, including chronic migraine, spastic disorders, cervical dystonia, and detrusor hyperactivity. The toxin, existing in different serotypes, primarily acts by inhibiting acetylcholine release at the neuromuscular junction, leading to muscle relaxation. FDA-approved indications encompass chronic migraine, cervical dystonia, blepharospasm, and cosmetic improvements in glabellar lines. The toxin's efficacy extends to conditions like hyperhidrosis and neurogenic detrusor overactivity.

Despite its therapeutic benefits, there are contraindications that include keloidal scarring, neuromuscular disorders, and allergies to botulinum toxin. Adverse effects are typically mild, ranging from bruising to flu-like symptoms, with rare occurrences of more severe complications like eyelid ptosis. Diligent screening and monitoring are crucial to ensure patient safety. 

Serious events from systemic spread of botulinum toxin can lead to botulism-like features or systemic anaphylactic reactions. Cosmetic use generally has fewer severe side effects compared to therapeutic applications. Diffusion of botulinum toxin to adjacent muscles may cause dysphonia or dysphagia. Severe dysphagia may require temporary dietary changes or even intravenous nutrition. Early administration of botulinum antitoxin serum is crucial for treatment. Antibody formation and immunoresistance can develop, affecting about 1% of patients receiving long-term, high-dose treatments. 

The toxin's duration of action varies, lasting three to five months in cosmetic applications and up to nine months for certain therapeutic uses. Specific dosages and dilution guidelines are provided for each FDA-approved preparation, with considerations for aesthetic improvements and therapeutic applications. The drug's pharmacokinetics reveal undetectable levels in peripheral blood following intramuscular injection. Special considerations are outlined for various patient populations, including pediatric and geriatric patients. While generally safe, the toxin carries a boxed warning due to potential systemic effects beyond the injection site, emphasizing the need for careful monitoring.

The interprofessional healthcare team, comprising primary care physicians, specialists, and nurses, play a crucial role in assessing patient eligibility, administering injections, and monitoring outcomes. Communication with patients about expected outcomes, potential risks, and post-treatment care is essential for ensuring optimal results and patient satisfaction. In my previous rotation, I was at a compounding pharmacy called AmeriCare where pharmacists had to counsel patients receiving Botox injections. The owners of the pharmacy had a beauty salon next door which allowed the two businesses to be tied together. 

Botulinum toxin's off-label uses include addressing conditions like neurogenic thoracic outlet syndrome, epicondylitis, post-stroke pain, post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, neuropathic pain, spinal cord injury, myofascial pain, and bladder pain. Its mechanism of action involves binding to extracellular receptors on cholinergic nerve terminals, inhibiting the release of acetylcholine and potentially alleviating chronic pain disorders, migraines, and neuralgias.

The toxin's administration requires careful attention, with preparations like OnabotulinumtoxinA, AbobotulinumtoxinA, IncobotulinumtoxinA, and RimabotulinumtoxinB having specific dilution guidelines. Aesthetic applications, particularly for glabellar lines, necessitate precise dosages to achieve the desired effects.

In conclusion, botulinum toxin stands as an FDA-approved medication with diverse therapeutic and cosmetic applications. While offering significant benefits, it requires careful consideration of patient eligibility, dosage, and potential adverse effects. 

References:

Bai L, Peng X, Liu Y, et al. Clinical analysis of 86 botulism cases caused by cosmetic injection of botulinum toxin (BoNT) Medicine (Baltimore) 2018;97:e10659

Bentivoglio AR, Del Grande A, Petracca M, Ialongo T, Ricciardi L. Clinical differences between botulinum neurotoxin type A and B. Toxicon. 2015 Dec 01;107(Pt A):77-84.

Padda IS, Tadi P. Botulinum Toxin. [Updated 2023 Nov 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-

Paget SP, Swinney CM, Burton KLO, et al. Systemic adverse events after botulin neurotoxin A injections in children with cerebral palsy. Dev Med Child Neurol. 2018;60:1172–7

Park J, Park HJ. Botulinum Toxin for the Treatment of Neuropathic Pain. Toxins (Basel). 2017 Aug 24;9(9) 

Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014 Feb;7(2):31-9.

Botox is a common term used in the cosmetic industry to achieve a desired physical appearance. Botox is medically termed, Botulinum Toxin, and it is derived from a culture of the Hall strain of C. botulinum and purified by a series of acid precipitations to a crystalline complex. When injected, it works by blocking nerve signals to muscles and contract them. This tense effect on the muscle is due to inhibition of the neurotransmitter, acetylcholine from the presynaptic cell. (3) This effect is temporary and can last several months. There are eight different strains of botulinum toxin for cosmetic or medical purposes. Type A botulinum toxin was used for the treatment of strabismus or cross eye. It was coined “the miracle poison” for its effectiveness to align the eyes and improve blurriness. Stereotype A or onabotulinumtoxinA is the common formulation available for clinical use and is prepared as, Botox®, in the US. Type B or rimabotulinumtoxin B is branded as Myobloc® and injected for neck pain.

Once the preparation is reconstituted it must be administered within four hours and kept refrigerated. Each dose is adjusted based on patient needs, muscle mass and type of operation. This drug appeals to the public if they are looking to reverse or prevent signs of aging. The muscle injected can smooth fine lines and wrinkles on the forehead, eyes to reduce crow’s feet, the jawline, eyebrows and more. Botox is also administered for medical conditions and pain management. (4) Cervical dystonia or neck spasms, eyelid twitches, hyperhidrosis or excessive sweating, chronic migraines, overactive bladder are a few conditions that can be corrected with Botox injections. If a patient experiences chronic pain in their back, neck, pelvis, sciatica or temporomandibular joints (TMJ), relief and relaxation with an injection can be added to their treatment regimen when consulting with their medical provider.

Botox injections can take 1 to 3 days after treatment to see or feel affects and up to one week for full results. Generally, a single dose can last up to three months before another consultation is recommended. (2) Botox is an outpatient procedure where you may receive multiple injections depending on the procedure. After the procedure, do not rub the area for twenty-four hours and stay upright for four hours to prevent the dose from spreading to unwanted areas. Also, avoid extraneous physical exertion for twenty-four hours. For cosmetic procedures, side effects are usually well-localized, reversible, and self-limited complications that can arise within the first few days of the procedure. The most common are either injection-site or technique-type side effects.

If there is bruising, erythema, or discoloration, it is caused by an injury to a blood vessel during injection and can be treated with an icepack. (2) Another side effect can be dry skin caused by decreased sweat gland activity. This can be treated with emollients such as Eucerin or Aquaphor. A technique-type side effect can be “mephisto look” or a hyper-elevation of the eyebrows or exaggeration of wrinkles. Correct dose and technique will correct this effect. Overall, Botox procedures can benefit the patient’s self-esteem with cosmetic regimens or improve quality of life with medical treatments.

References:

1.“Botox Injections.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 10 Mar. 2023, www.mayoclinic.org/tests-procedures/botox/about/pac-20384658.

2.Cleveland Clinic medical. “Botox Injections: Treatment, Recovery & Side Effects.” Cleveland Clinic, my.clevelandclinic.org/health/treatments/8312-botulinum-toxin-injections.

3.Nigam, P K, and Anjana Nigam. “Botulinum Toxin.” Indian Journal of Dermatology, U.S. National Library of Medicine, 2010, www.ncbi.nlm.nih.gov/pmc/articles/PMC2856357/#:~:text=%5B14%5D%20Botox%C2%AE%20is%20a,the%20toxin%20and%20other%20proteins.

4.Witmanowski, Henryk, and Katarzyna Błochowiak. “The Whole Truth about Botulinum Toxin - A Review.” Postepy Dermatologii i Alergologii, U.S. National Library of Medicine, Dec. 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7874868/.

Botox Injections and Side Effects for Chronic Migraines 

Yu Feng Lin & Fawziya Twam

Botox injections have gained popularity over the years, but how many actually know what it is and the risks that come with it? Botox injections, as in its name, are given as injections. The botox, or the drug injected, is a toxin produced by the bacterium clostridium botulinum. The toxin has the ability to cause botulism, which is a life-threatening type of food poisoning. To be approved by the U.S Food and Drug Administration, the toxin is given in small and controlled doses. The proper use of the toxin in very small amounts, leads to the temporary prevention of muscle movement. When giving botox injections, the general goal is to stop muscle movement. The way the botox works is by weakening or paralyzing the muscles. The effects of botox can last from 3 months to 12 months, depending on what is being treated. Botox injections are commonly given repeatedly in order to achieve the desired effects. One big reason botox injections are used is to smooth facial wrinkles, thus improving one's appearance. However there are many other reasons botox is used. While botox can be useful in cosmetology, some of its uses are to treat disorders. Chronic migraine, overactive bladder, cervical dystonia, and blepharospasm being a few. Cervical dystonia is a neurological disorder. It causes severe neck and shoulder muscle contractions. These contractions can be painful and negatively affect a person’s quality of life. Blepharospasms is when a patient experiences uncontrollable blinking. One common use of botox, whether cosmetic or not, is it is used to increase a person’s quality of life. 

Many may be familiar with the effects of botox on the skin. Muscle movement is restricted and therefore wrinkles are reduced. This may be an achievement many have seen. But how does botox treat chronic migraine? Neuromodulating drugs are drugs used in the treatment of chronic migraines. Their use was approved by the Food and Drug Administration in 2010. If a person has a headache at least 15 days of the month, they may be diagnosed with chronic migraines. While botox injections may not be the first course of action, treating chronic migraines has proven to be a challenge in many patients. In certain cases, the patient may be an option. Botulinum toxin-based drugs aid in the reduction of migraine by interrupting the pathway of pain transmission between the central nervous system and the nerves which extend from the spinal cord. Migraine pain comes from neurotransmitters. By interrupting the pathway, the neurotransmission no longer occurs. Therefore, the pain that would have taken place, will no longer be present. To use botox for migraines, the injections are into certain muscles around the face, head and neck. Relief can be seen after about 4 weeks. In some cases another round of botox is needed before seeing results. There are patients who stop the treatment and say the frequency of migraines remains low, while others must continue to receive treatment or the headaches return. 

The way botox injections are used for chronic migraines is using a very small needle to inject certain muscles. A specialist will inject the botox under the skin in various areas around the face, in the head and neck. Common areas include the forehead, temples, the back of the neck and the back of the head. Trigger points will vary from patient to patient. The trigger point is where the migraine or the pain originates from. Depending on the location of the trigger point, it may be injected as well. Using botox for headaches has its benefits, but it also has its risks. A common experience is pain, bruising or swelling where the drug is injected. This is a common effect with just about any injection. Other possible side effects include a headache, or flu like symptoms. Normally this doesn't last very long if it does occur. Because of the way botox works and its effects on muscles, there are times where it can cause a droopy eyelid, eyebrow or on one side of the mouth. This is not a permanent side effect and should resolve on its own. The eyes may be dry or watery as well. In some cases, drooling can be seen as well. This is also due to the paralyzation of the muscles. The side effects discussed are not ones to be concerned about. They do not occur frequently and do not last long. However in extremely rare occurrences. The toxin may spread into the body. As mentioned earlier, botox is a toxin and can be deadly. If certain side effects are experienced, medical attention is required immediately. Side effects include, changes in vision, muscle weakness, trouble speaking or swallowing, difficulty breathing and/ or the inability to  control one's bladder. Overall, botox can be a helpful tool in treating chronic migraines. It is crucial for botox to be done by specialists who are knowledgeable in the use of botox. Botox can be helpful when used in a proper and controlled setting, meanwhile can be very dangerous if used improperly. 

References

U.S. National Library of Medicine. (n.d.). Botox | botulinum toxin | botox injections. MedlinePlus. https://medlineplus.gov/botox.html 

Mayo Foundation for Medical Education and Research. (2023, March 10). Botox injections. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658#:~:text=Botox%20injections%20are%20shots%20that,lazy%20eye%20and%20other%20conditions. 

Botulinum toxin injectables for migraines. Johns Hopkins Medicine. (2021, October 15). https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/botulinum-toxin-injectables-for-migraines 

BOTOX AND SIDE EFFECTS

Botulinum toxin is derived from bacteria and is used in injection form that is available in different types. The subtypes of Botox are A, B, C1, D, E, F, and G. Clinically, toxins A and B are the ones used. Formulations of Botox types A include onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA. The mechanism of action of Botox is that it inhibits acetylcholine release from peripheral nerve cells, which suppresses muscle contraction. Botox has been used in different cosmetic settings. This includes facial lines and wrinkles, forehead lines, crow's feet, frown lines, nasal flares, and gummy teeth. In addition, Botox A has also been approved to treat chronic migraines. It is injected into multiple sites on the head and neck, every 3 months. It has been approved for patients 18 years and older with migraine days for more than half the month (15 days or more). Botox type B, available as RimabotulinumtoxinB, is mainly used for cervical dystonia, which is involuntary neck muscle contractions. Evidence has also shown the effectiveness of Botox in the treatment of hyperhidrosis. Overactive bladder and urinary incontinence can also be treated with Botox. Once receiving the Botox injection, the results begin to show in one to three days. However, peak results occur one to four weeks post-injection. The duration of the injection depends on dose, formulation, and injection site, but it typically lasts for three or four months. After multiple injections at the same site, results can last for at least six months. If the desired outcome is not achieved with Botox alone, it can be combined with cosmetic fillers, lasering, micro-focused ultrasounds, or facial surgeries.

People who should not receive a Botox injection are those with an infection, psoriasis, or eczema on the site of desired infection and those with allergies to any of the ingredients inside Botox. People with cow's milk protein allergies should not be injected with AbobotulinumtoxinA but can receive injections of onabotulinumtoxinA, incobotulinumtoxinA, or rimabotulinumtoxinB. Patients with neurological disorders, such as myasthenia gravis or Eaton-Lambert syndrome, can experience severe muscle weakness. Increased muscle fatigue can be seen in patients taking gentamycin, amikacin, tobramycin, and neomycin. Pregnant women should not receive OnabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB injections, however, not enough evidence is available in regard to prabotulinumtoxinA. Side effects include pain and bruising from the injection site, which may be treated with ice or topical analgesics. After multiple injections, muscle atrophy, or muscle waste, can occur. If the facial Botox diffuses and spreads, it can cause brow and eye drooping, teary eyes, and double vision. Other symptoms that can be seen include facial paralysis, pneumonia, respiratory compromise, difficulty swallowing, and headaches. Botulism, which is bacterial food poisoning, can occur as well. Speaking with your doctor is the best way to see if Botox is right for you. Be sure to inform the doctor of allergies, disorders, medications, and if you are taking contraceptives or are pregnant.

Althawadi N, Ujam A, Visavadia B. Botox hidden dangers. Br Dent J. 2022 Feb;232(4):192-193. doi: 10.1038/s41415-022-4006-3. PMID: 35217725.

Botox for chronic migraine. Drug Ther Bull. 2011 Feb;49(2):22-4; quiz iii-iv. doi: 10.1136/dtb.2010.10.0008. PMID: 21304165.

Brin MF, Burstein R. Botox (onabotulinumtoxinA) mechanism of action. Medicine (Baltimore). 2023 Jul 1;102(S1):e32372. doi: 10.1097/MD.0000000000032372. PMID: 37499078; PMCID: PMC10374191.

Overactive bladder (OAB) is a common condition that affects millions of women worldwide. It is characterized by symptoms such as frequent urination, sudden urges to urinate, and involuntary leakage. While various treatment options exist, recent advancements have shown promising results in the use of Botox injections as an effective treatment for overactive bladder in women. 

Botox, also known as onabotulinumtoxin A, is a neurotoxin derived from the bacterium Clostridium botulinum. It works by temporarily paralyzing or relaxing the muscles where it is injected. In the case of OAB, Botox is administered directly into the bladder muscle. By inhibiting the release of acetylcholine, a neurotransmitter that stimulates muscle contractions, Botox helps to calm the overactive muscles of the bladder, reducing the frequency of urgency and incontinence episodes. The use of Botox for OAB in women has shown several significant benefits. Firstly, it provides long-lasting relief. Unlike oral medications that require daily intake, Botox injections provide relief for several months. This reduces the need for frequent medication management and enhances patient compliance. Additionally, Botox has been found to significantly reduce the number of daily voids, episodes of urgency, and incontinence episodes, leading to improved urinary control and overall quality of life. Numerous clinical trials and studies have demonstrated the efficacy and safety of Botox for OAB in women. One study published in The New England Journal of Medicine reported that Botox injections reduced daily voids by an average of three episodes, urgency episodes by 70%, and incontinence episodes by 50%. The treatment was well-tolerated, with only minimal side effects, including temporary urinary retention and urinary tract infections, which were easily managed. The impact of Botox treatment for OAB extends beyond symptom relief. Women who suffer from overactive bladder often experience a diminished quality of life, including social embarrassment, anxiety, and limitations in daily activities. Botox injections have been shown to improve these aspects significantly, allowing women to regain control over their bladder function and participate more fully in their personal and professional lives. Increased confidence and self-esteem are commonly reported benefits.

While Botox injections for OAB in women have shown remarkable efficacy and safety, several considerations should be taken into account. Firstly, Botox treatment is typically recommended after conservative treatments, such as lifestyle modifications and oral medications, have proven ineffective. Secondly, as with any medical intervention, it is important to discuss potential risks and benefits with a healthcare professional to make an informed decision. Future directions for the use of Botox in OAB treatment involve optimizing injection techniques and dosages to maximize effectiveness while minimizing side effects. Research is also ongoing to explore the use of Botox for other bladder-related conditions, such as neurogenic bladder and interstitial cystitis, to further expand treatment options for women suffering from these conditions.

Botox injections have emerged as a game-changer in the treatment of overactive bladder in women. By targeting the overactive muscles of the bladder, Botox provides long-lasting relief and improves urinary control, leading to enhanced quality of life for women who have been burdened by OAB symptoms. With its proven efficacy and safety profile, Botox is still considered a last line agent and should not be the first route in treatment. We can aide in the decision making with patients by giving them the risks and benefits and hoping they can make an informed decision 

Resources 

“A Study of the Effectiveness of Transvaginal Administration of Botulinum-a Toxin for the Treatment of Women with over Active Bladder (OAB) Syndrome.” Mayo Clinic, 16 July 2022, www.mayo.edu/research/clinical-trials/cls-20359596.

Since BOTOX (onabotulinumtoxinA) was first approved by the FDA in 1989 for two rare eye muscle disorders - blepharospasm and strabismus in adults - new indications have been developed and approved. OnabotulinumtoxinA is now FDA-approved for 12 therapeutic indications, including chronic migraine, overactive bladder, leakage of urine (incontinence) due to overactive bladder caused by a neurologic condition in adults, cervical dystonia, adult and pediatric spasticity, severe underarm sweating (axillary hyperhidrosis), and pediatric detrusor overactivity associated with a neurologic condition.

On April 15, 2002, the FDA approved BOTOX® as a temporary cosmetic treatment for moderate to severe frown lines in adults and requested the product be marketed as BOTOX® Cosmetic to distinguish cosmetic from therapeutic uses. BOTOX Cosmetic is a prescription medicine that has 3 FDA-approved areas - moderate to severe forehead lines, lateral canthal lines, and/or glabellar lines. It was the first treatment of its kind and today is the only product FDA approved to make moderate to severe frown lines, crow’s feet, and forehead lines look better in adults.

In general, the clinical effects of botulinum toxin begin to appear in one to three days, peak in one to four weeks, and gradually decline after three to four months. However, the duration of response is dependent upon the injection site, dose, and specific formulation of botulinum toxin utilized. Some patients, particularly those who have received repeated injections in the same area, may experience benefits for six months or longer. This may be at least partially due to the development of muscle atrophy.

When patients are appropriately selected and proper dosing and injection techniques are utilized, the use of botulinum toxin for cosmetic indications appears to be relatively safe. Side effects are usually mild and transient and most commonly include swelling or bruising at the injection site, mild headache, or flu-like symptoms . Undesired impairment of muscle function may also occur, but is usually associated with poor injection technique or inappropriate patient selection. Because smaller doses are less likely to cause unintended adverse effects, a conservative approach to treatment is advisable.

Examination of the available data on botulinum toxin reveals an impressive safety record. The authors of a 2004 systematic review and meta-analysis of randomized trials (n = 1425) found no reports of serious adverse effects in patients treated with onabotulinumtoxinA for medical or cosmetic purposes. Serious adverse effects reported to the FDA have also been low in number; between 1989 and 2003, only 36 serious adverse effects associated with cosmetic use were reported. Examples of the serious adverse effects that were documented included injection site reactions, headache, focal facial paralysis, muscle weakness, flu-like symptoms, dysphagia, respiratory compromise, cardiac arrhythmia, seizure, ocular abnormalities, and allergic reactions. Of note, 13 of the patients who experienced serious adverse effects had underlying medical conditions that may have contributed to the observed event (eg, respiratory compromise in a patient with asthma and cardiac arrhythmia in a patient with a history of heart murmur).

Although the risk of serious adverse effects is low with cosmetic use, side effects such as aspiration, dysphagia, pneumonia, anaphylaxis, botulism, and death have been reported in association with the use of botulinum toxin. As a result, in 2009, the US FDA instituted a requirement for boxed warnings on product labels and a Risk Evaluation and Mitigation Strategy for all botulinum toxin products.

Since the effect of botulinum toxin is temporary, patients require additional treatment to maintain improvement. The safety of repetitive treatment with botulinum toxin was evaluated in a retrospective study of more than 4000 treatments in 945 patients treated for lines in the upper face. Patients had to have received a minimum of three consecutive treatment cycles. Only mild to moderate adverse effects were detected; bruising and ptosis were most common. In addition, the incidence of side effects decreased with repeated injections, a finding that has been reported in studies of the medical use of botulinum toxin type A. Repeat injections with abobotulinumtoxinA have also been well tolerated in large open label studies.

References:

1. BOTOX® Cosmetic (Boe-tox) (onabotulinumtoxinA) for Injection. (2021, February). U.S. Food and Drug Administration. Retrieved from https://www.rxabbvie.com/pdf/botox_medguide.pdf

2. Carruthers, J. (2022, November 8). Overview of botulinum toxin for cosmetic indications. UpToDate. Retrieved from uptodate.com/contents/overview-of-botulinum-toxin-for-cosmetic-indications#H522914

3. Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin 2004; 20:981.

4. Rzany B, Dill-Müller D, Grablowitz D, et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg 2007; 33:S18.

Botox Injections and Side Effects

Botulinum toxin, commonly known as botox, is commonly used for the treatment of facial wrinkles. Frown lines, crows feet, and horizontal forehead lines are commonly treated with botox in the United States. Botulinum toxin is derived from the Clostridium botulinum bacterium. Injection into muscles inhibits the release of acetylcholine at the neuromuscular junction which blocks contraction of muscle. This process is called chemical denervation. Repetitive contraction of facial muscles leads to wrinkle formation. Botulinum toxin relaxes the facial muscles and smooths the skin. Most muscles in the body have bony attachments to the skin, so the skin does not move upon contraction. The skin on the face is attached to muscle through soft tissue allowing for movement upon contraction. Patients with wrinkles upon movement are the best candidates for botox treatment. Results are less dramatic for patients with wrinkles upon rest as it may take a few consecutive botulinum toxin treatments to see improvement.

Botulinum toxin type A is used for cosmetic procedures while Botulinum toxin type B is used for conditions like dystonia. FDA approved botulinum toxin serotype A products include: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). IncobotulinumtoxinA does not contain complexing proteins which may reduce its antigenicity and formation of antibodies in the body. Further research must be done to confirm this.

Doses are usually 1 mL or less with one injection in the procerus muscle and two injections in each of the corrugator supercilii muscles (Small R.). Results should be seen within 3 days and maximum results should be visible at 2 weeks after treatment. Results should last for about 3 to 4 months and treatment should be given again when there is visible muscle movement. Injection reactions include anxiety, erythema, headache, infection, or pain. Bruising and redness are common. NSAIDs can be used for treatment of headaches. Botulinum toxin side effects include allergic reaction, spreading from the injection site, eyebrow ptosis, or facial asymmetry.

The amount of procedures using botulinum toxin A is expanding. Studies have shown that botulinum toxin A can have an effect on hypertrophic scars. It can inhibit fibroblast proliferation and downregulate expression of actin and myosin II proteins. It may also inhibit TGF-B1 and connective tissue growth factor. The effect of botulinum toxin on vascular endothelial growth factor (VEGF) to promote new vessels for wound healing is not known, but it may be possible. There has not been as much promise for the treatment of keloids as there is for facial hypertrophic scars. The use of botulinum toxin A and dermal fillers together may enhance the effect. Fillers have a longer duration of action than botulinum toxin which may help to extend the duration of the effect. They may assist each other in improving the smoothness of the skin. Furthermore, using a skincare regimen that consists of a retinoid helps to protect the patient from photodamage. The use of botulinum toxin intradermally is another area of focus for research. There are current studies researching its effect for bruxism, psoriasis, pain, and rosacea. Botulinum toxin may help with rosacea by inhibiting acetylcholine which is responsible for redness and flushing. It may help acne by blocking acetylcholine in sebocytes. Many other skin diseases are caused by hyperhidrosis which can be treated with botulinum toxin A. Botulinum toxin is a powerful substance requiring further research for all of its possible uses.

Schlessinger, J., Gilbert, E., Cohen, J. L., & Kaufman, J. (2017). New Uses of AbobotulinumtoxinA in Aesthetics. Aesthetic surgery journal, 37(suppl_1), S45–S58. https://doi.org/10.1093/asj/sjx005

Small R. (2014). Botulinum toxin injection for facial wrinkles. American family physician, 90(3), 168–175.