OnabotulinumtoxinA - Limitations and Clinical Studies

Warning

OnabotulinumtoxinA has the potential to reach distant tissues and result in changes parallel to that of OnabotulinumtoxinA symptoms. The effects that OnabotulinumtoxinA produces are reported to come into the picture after a few hours to weeks of exposure to OnabotulinumtoxinA. Difficulty in breathing and obstruction while swallowing are the two life-threatening consequences of OnabotulinumtoxinA reported. Children and adults with underlying medical conditions are highly prone to developing serious risks to OnabotulinumtoxinA, and deaths have also been reported.

What Are the Major Changes That Have Been Recently Done With OnabotulinumtoxinA?

Recent major changes of OnabotulinumtoxinA are the following.

• Indications of OnabotulinumtoxinA.

• Usage for chronic migraine.

• Dosage of OnabotulinumtoxinA for chronic migraine.

• Administration changes for OnabotulinumtoxinA.

What Are the Major Limitations of OnabotulinumtoxinA?

It is important to be aware of the limitations of any drug.

Mentioned below are the major limitations of OnabotulinumtoxinA.

• The effectiveness and safety of OnabotulinumtoxinA for the preventive treatment of migraine episodes have not yet been established.

• The effectiveness and safety of OnabotulinumtoxinA for the management of spasticity of the upper limb as well as the lower limb in the pediatric group of patients have not yet been established.

• The effectiveness and safety of OnabotulinumtoxinA in adults for treating spasticity of lower limbs have not yet been established.

• The effectiveness and safety of OnabotulinumtoxinA in cases of hyperhidrosis other than axillary areas have not yet been established.

What Are the Clinical Studies Done on OnabotulinumtoxinA?

It should be noted that clinical studies and trials are done under hugely different conditions. Due to this, the adverse effects and rates of abnormal reactions cannot be considered to be parallel to the rates reported in clinical practice. OnabotulinumtoxinA or cosmetics containing OnabotulinumtoxinA hold the same potential for any adverse effects or symptoms of the toxin. Clinical studies have shown that any adverse effects generally occur within the initial week of administration of OnabotulinumtoxinA. The adverse effects may last for several months to weeks.

Mentioned below are the associated signs with injection.

• Infection at the site of injection.

• Inflammation or swelling.

• Localized pain.

• Tenderness.

• Swelling.

• Bruising of the skin.

• Abnormal bleeding.

• Syncope.

• Erythema.

• Hypotension.

• Anxiety.

• Vasovagal syncope.

• Weakness of nearby muscles.

Mentioned below are the clinical studies done on OnabotulinumtoxinA for various conditions.

1) Chronic Migraine - In a double-blind placebo-controlled trial of migraine, the rate of discontinuation of OnabotulinumtoxinA was 12 % amongst those treated with OnabotulinumtoxinA and 10 % among those in the placebo group. The individuals treated with OnabotulinumtoxinA who discontinued the treatment were 4 % and 1 % in the placebo group. Neck pain, worsening of the migraine, headache, and ptosis of the eyelid were the most common effects that led to the discontinuation of OnabotulinumtoxinA amongst the study participants.

Mentioned below are the most common adverse effects of OnabotulinumtoxinA treatment in patients suffering from episodes of chronic migraine.

• Headache.

• Worsening of migraine.

• Eyelid ptosis.

• Facial paresis.

• Bronchitis.

• Neck pain.

• Muscle spasm.

• Myalgia.

• Muscular weakness.

• Musculoskeletal stiffness.

• Pain at the site of injection.

• Hypertension.

• Vertigo.

• Edema of the eyelids.

• Infection of the eyes.

• Pain in the jaws.

• Dry eyes.

• Difficulty in swallowing.

2) Spasticity of the Upper Limbs - The adverse effects that have been reported in patients suffering from the spasticity of upper limbs who have undergone treatment with OnabotulinumtoxinA for the same include nausea, bronchitis, weakness of the muscles, fatigue, and pain in the extremities.

3) Cervical Dystonia - In a double-blind, open-labeled study, the evaluation of the safety of OnabotulinumtoxinA leads to the conclusion that dysphagia or difficulty in swallowing is one of the most common adverse effects of OnabotulinumtoxinA in patients suffering from cervical dystonia. Other than this, neck pain, headache, and infection of the upper respiratory tract are also reported. Furthermore, in case the treatment with OnabotulinumtoxinA is extended in patients with cervical dystonia, muscle weakness and difficulty in swallowing may build up over time.

The other adverse effects of clinical studies done on patients with cervical dystonia under OnabotulinumtoxinA treatment are mentioned below.

• Ptosis.

• Diplopia.

• Stiffness.

• Numbness.

• Dyspnea.

• Fever.

• Nausea.

• Drowsiness.

• Hypertonia.

• Soreness.

• Dryness of the mouth.

• Disorders with speech.

• Dizziness.

• Rhinitis.

• Signs similar to flu.

• Increased frequency of cough.

• Back pain.

4) Primary Axillary Hyperhidrosis - In a double-blind study after injecting with OnabotulinumtoxinA, the data reflected pain at the site on injection, hemorrhage, infection, signs similar to flu, fever, headache, pruritus, anxiety, neck pain, and pharyngitis in around three to ten percent of the participants.

5) Blepharospasm - In a study, individuals who have received injections at three to five sites have reported adverse effects such as dryness of the eye, ptosis, superficial punctate keratitis, entropion, swelling of the eyelid, keratitis, irritation of the skin as well as rashes. Other less frequent reactions were photophobia, tearing, lagophthalmos and ectropion. There have been two cases of patients suffering from a seventh nerve disorder that have reported reduced blinking as a result of swelling of the orbicularis muscle and corneal exposure.

6) Strabismus - Extraocular muscles develop vertical deviation as reported in several studies. The injected muscle has been reported to have 1 % of ptosis in the injection of the inferior rectus, 16 % in the injection of the horizontal rectus, and 38 % in the superior rectus.

What Are the Post Marketing Experiences of OnabotulinumtoxinA?

There have been reports of immediate death after OnabotulinumtoxinA along with pneumonia, dysphagia, and anaphylactic reaction. There have also been several reports of reactions involving vital organ systems, such as the cardiovascular system, leading to arrhythmia or myocardial infarction with a few fatal outcomes. The exact relationship between OnabotulinumtoxinA and the cardiovascular system has not been established yet.

Mentioned below is the post-marketing experience on OnabotulinumtoxinA, which has not been mentioned in the package.

• Abdominal pain.

• Anorexia.

• Brachial plexopathy.

• Diarrhea.

• Facial palsy.

• Facial paresis.

• Hyperhidrosis.

• Hyperacusis.

• Hypoaesthesia.

• Localized numbness.

• Malaise.

• Myalgia.

• Paresthesia.

• Pyrexia

• Radiculopathy.

• Skin rash.

• Erythema multiforme.

• Psoriasiform eruption.

• Tinnitus.

• Vertigo.

• Visual disturbances.

• Vomiting.

OnabotulinumtoxinA For Doctors

OnabotulinumtoxinA is a sterile injection that is vacuum-dried and purified. It is produced from the process of fermentation of Hall strain Clostridium botulinum type A. OnabotulinumtoxinA is indicated for intradermal and intramuscular usage. The culture solution is purified via dialysis following a sequence of acid precipitation. This ends up in a complex neurotoxin and several other accessory proteins. This complex is then mixed in a sterile solution of sodium chloride that has Albumin Human. With the help of a cell-based potency assay, OnabotulinumtoxinA is cultivated.

Warning

OnabotulinumtoxinA has the potential to reach distant tissues and result in changes parallel to that of OnabotulinumtoxinA symptoms. The effects that are produced by OnabotulinumtoxinA are reported to come into the picture after a few hours to weeks of exposure to OnabotulinumtoxinA. Difficulty in breathing and obstruction while swallowing are the two life-threatening consequences of OnabotulinumtoxinA that have been reported. Children and adults with underlying medical conditions are highly prone to developing serious risks to OnabotulinumtoxinA, and deaths have also been reported for the same.

When Is OnabotulinumtoxinA Indicated?

OnabotulinumtoxinA is a chemical agent that blocks the neuromuscular junction and thus decreases the release of acetylcholine. Acetylcholine is an important part of the ANS or autonomic nervous system. It leads to the contraction of muscles, the dilation of arteries and veins, decreases the heart rate, and increases the secretion of bodily fluids. Being a neurotransmitter, acetylcholine aids in the smooth functioning of the brain.

OnabotulinumtoxinA works by blocking acetylcholine and is thus indicated in the below-mentioned conditions.

• Prophylaxis of chronic migraine in adults.

• Treating the spasticity of the upper limb in adults.

• Correction of severe cervical dystonia in adults.

• Treatment of crossed eyes, known as strabismus in patients who are twelve years or more.

• Preventive treatment of long-lasting headaches in adults.

• Management of axillary hyperhidrosis in adults that is severe in nature.

• Correction of uncontrolled twitching of the eyes, known as blepharospasm in patients who are twelve years or more.

What Are the Recommended Administration and Dosage of OnabotulinumtoxinA?

It is suggested to strictly follow the recommended administration and dosage instructions. A combined dose of three hundred and sixty units must not be exceeded while administering every twelve to sixteen weeks or more. Additionally, patients are advised to ask their respective healthcare providers for instructions regarding the administration and dosage of OnabotulinumtoxinA for better understanding and clarification.

Mentioned below are the recommended administration and dosage of OnabotulinumtoxinA.

• The recommended combined dose for the treatment of chronic migraine is one hundred and fifty-five units. Five injection units of 0.1 mL for each site are divided into seven head and neck muscles.

• The recommended dose for spasticity of the upper limb is based on the muscles that have been affected, the severity of muscle deformity, the response of the muscle to prior treatment modalities, and the history of adverse reactions. For the mentioned reasons, it is recommended to go for electromyographic guidance before prescribing the administration and dose limits of OnabotulinumtoxinA for such patients.

• The recommended dose for cervical dystonia is based on the position of the patient’s neck and head, the exact location of discomfort, hypertrophy levels of the affected levels, response of the patient to prior treatment measures, and history of any adverse reactions. It is suggested to start the patient on a lower dose initially, especially in patients who are ingenious to OnabotulinumtoxinA.

• The recommended dose for hyperhidrosis in axillary areas is fifty units per axilla.

• The recommended dose for blepharospasm is 1.25 units to 2.5 units into three sites of the affected eye each.

• The recommended dose for strabismus is initially 1.25 units to 2.5 units into any single muscle.

What Are the Dosage Formulations and Available Strengths of OnabotulinumtoxinA?

OnabotulinumtoxinA injection is for a single-use only. The available strengths of sterile OnabotulinumtoxinA injection start from fifty units, hundred units, up to two hundred units. The powder, which is vacuum-dried, can only be amalgamated with an injection of 0.9 % Sodium Chloride injection that is non-preserved and sterile.

What Are the Preparation Methods and Dilution Techniques of OnabotulinumtoxinA?

The vial of OnabotulinumtoxinA is available in single-use units of fifty, hundred, and two hundred. An injection is prepared by pulling out a sterile syringe whose size is slightly more than required. The amount of OnabotulinumtoxinA should be moderately more prominent than the required dose. The patency of the needle is confirmed beforehand. Before injecting, the OnabotulinumtoxinA content is reconstituted into a non-preserved, sterile 0.9 % of sodium chloride syringe. With reference to the dilution table, the drug is diluted. OnabotulinumtoxinA must be inserted twenty-four hours after reconstitution. Within this time frame, OnabotulinumtoxinA can be stored between the temperatures of two and eight degrees celsius. In case OnabotulinumtoxinA is removed, a new vial must be introduced. The reconstituted OnabotulinumtoxinA looks colorless, clear, and free of impurities or particles.

Mentioned below are the preparation methods and dilution techniques of OnabotulinumtoxinA for specific conditions.

• Chronic Migraine:

Two hundred units per foul mL or hundred units per two mL is the recommended dose of OnabotulinumtoxinA for chronic migraine. The final concentration is five units per 0.1 mL. Administration of one hundred fifty-five units is the recommended dose for the treatment of chronic migraine. This dose is administered through the intramuscular route via a sterile 0.5-inch needle, thirty gauges in the form of 0.1 mL, or five units of injection on each site. The injections are divided into seven specified head and neck areas. For regions with thick muscles such as the neck, a one-inch needle. All the muscles are bilaterally injected with twelve-week retreatment.

• Upper Limb Spasticity:

According to the size, the initial dosing and the sequence of treatment are modified. The location of the muscles that are involved, as well as the number of muscles, also play a decisive role in the treatment plan. A hundred units to two hundred units are divided into four sites.

• Cervical Dystonia:

For cervical dystonia, 263 units were the mean dose of OnabotulinumtoxinA. It was divided equally into the muscles that had been affected. The recommended dosage is prescribed after taking into consideration the amount of muscle hypertrophy, the response of the patient, and the location of the pain. In case there is a lot of discomfort during swallowing, the dosage of OnabotulinumtoxinA can be brought down to hundred units. The dilution of OnabotulinumtoxinA for cervical dystonia is two hundred units per two mL or four mL or hundred units up to one mL or two mL. For each site, the limit of insertion is fifty units.

• Primary Axillary Hyperhidrosis:

The dose for each site of the axilla is fifty units. The Minor’s Iodine-Starch Test is done before the selection of the site. The dilution should be a hundred units per four mL.

• Blepharospasm:

The OnabotulinumtoxinA must always be reconstituted for blepharospasm. The injection can be given without any electromyographic guidance. It is reported that the effect of OnabotulinumtoxinA can be reduced over repeated usage. The dosage of OnabotulinumtoxinA should not be more than two hundred units over a period of thirty days.

• Strabismus:

OnabotulinumtoxinA is injected into the extraocular muscles of the eyes after implementing the reports of the electrical activity of the eye. It should be known that OnabotulinumtoxinA should not be attempted for strabismus after surgical exposure to the eye. The eye should be prepared with drops of anesthetic solution.

What Are the Contraindications of OnabotulinumtoxinA?

OnabotulinumtoxinA may be harmful to some patients.

Mentioned below are the contraindications of OnabotulinumtoxinA.

• History of adverse reactions to OnabotulinumtoxinA and related products.

• Ongoing infection at the site of injection.

What Are the Precautions to Be Taken With OnabotulinumtoxinA?

Precautions with any drug should be taken into consideration before going ahead with therapy. This is because some reactions in the body may cause serious aftermaths. It is always better to keep such adverse reactions at bay rather than treat them, which may itself be a hassle.

Mentioned below are the precautions to be taken with OnabotulinumtoxinA.

• The spread of OnabotulinumtoxinA and its effects that may lead to death are difficulties in breathing as well as swallowing. The symptoms of OnabotulinumtoxinA had clearly shown that it could move up to the neighboring tissues and cause its effects. The symptoms are also parallel to ptosis, dysphonia, dysphagia, weakness of the muscles, inconsistency with the urine, dysarthria, and difficulties in breathing. The risk of this distant spread is more in children and adults with underlying conditions as compared to others. Even at lower doses, studies have shown the presence of a majority of these symptoms. There has not been any life-threatening outcome due to these changes at a recommended dose of thirty units or below other than death due to difficulty in swallowing or breathing. The reason for this is the loss of muscle tonicity in the neck after treatment with OnabotulinumtoxinA. This makes the patient lose their breathing capacity. Respiratory failure has also been reported due to dysphagia.

• Obstruction of the respiratory system or difficulties while speaking and swallowing require immediate attention.

• The effects of OnabotulinumtoxinA may be exacerbated by underlying disorders of the neuromuscular junction, such as extreme difficulty in breathing and difficulty in swallowing.

• OnabotulinumtoxinA should be administered with precaution in patients suffering from an ongoing respiratory system disorder.

• Ulcerations in the body due to persistence in epithelial defects especially, in patients with severe nerve disorders. The treatment of such epithelial defects must be strongly employed.

• Exposure to the cornea can be addressed by using soft lenses, eye patches, protective eye drops, and ointments.

• Retrobulbar hemorrhages in order to compromise retinal blood circulation have also been reported. The orbit should be appropriately decompressed in order to become accessible.

• Patients are suffering from a compromised circulation of the retina.

• Patients suffering from infections of the upper respiratory tract as well as bronchitis have frequently been reporting adverse reactions to OnabotulinumtoxinA.

• Patients with a long-standing history of viral diseases and their transmission.

What Are the Adverse Reactions of OnabotulinumtoxinA?

The adverse effects of OnabotulinumtoxinA have been established after several controlled studies. Headache and neck pain were found to be two of the most common side effects associated with OnabotulinumtoxinA.

Mentioned below are the adverse reactions that have been observed with OnabotulinumtoxinA.

• Neck pain.

• Headache.

• Pain in the extremities.

• Difficulty in swallowing food or water.

• Rhinitis.

• Infection of the upper respiratory tract.

• Increased intensity and frequency of cough.

• Signs and symptoms parallel the flu.

• Pain in the entire body, especially the back.

• Infections such as rhinitis.

• Discomfort or pain at the site of the injection.

• Occurrence of hemorrhage.

• Inflammation of the pharynx, also known as a sore throat.

What Are the Drug Reactions With OnabotulinumtoxinA?

Patients who have been chosen for the treatment and therapy with OnabotulinumtoxinA, should not receive any drug agent that interacts with the neuromuscular junction. Additionally, such patients should not be treated with muscle relaxants as well. Patients who are receiving therapy with aminoglycosides or similar drugs also come into this category. In case treatment with these agents are necessary due to medical reasons, the patients should be under strict monitoring and scrutiny since interactions between aminoglycosides or OnabotulinumtoxinA with muscle relaxants or drugs indicated for neuromuscular transmission may have the potential to be life-threatening.

What Are the Immunogenicity Factors of OnabotulinumtoxinA?

It should be known that every protein used for the purpose of therapy has the potential for immunogenicity. In the case of OnabotulinumtoxinA, the action and effectiveness of this drug are reduced after there is the formation of any kind of antibodies. Out of four patients in an open-labeled study, three patients developed immunogenicity to OnabotulinumtoxinA, while one of them responded well to OnabotulinumtoxinA. Only a single patient amongst the four hundred above patients suffering from hyperhidrosis, two patients among the three hundred above patients suffering from spasticity of the upper limb, and no patient among the four hundred above patients suffering from migraine patients developed the presence of antibodies. The differentiating factors for the formation of antibodies have not been well distinguished. Several studies have reported that administration of OnabotulinumtoxinA at a higher dose is directly proportional to the development of antibodies and thus immunogenicity.

What Are the Drug Interactions With OnabotulinumtoxinA?

There have not been any studies between OnabotulinumtoxinA and other drugs. For this reason, there is no established drug interaction with OnabotulinumtoxinA. It has been reported that OnabotulinumtoxinA has an accentuated effect when used along with aminoglycosides or similar agents. Thus, the utmost caution should be taken when using OnabotulinumtoxinA with similar agents. A muscle relaxant before administration of OnabotulinumtoxinA may lead to excessive muscle weakness. Administration of OnabotulinumtoxinA along with similar OnabotulinumtoxinA toxins or other products have proved to result in weakness of neuromuscular junctions.

What Are the Uses of OnabotulinumtoxinA in Special Populations?

• Pregnancy:

There have not been a lot of studies on pregnant patients, and thus there is no adequate report on the efficiency and safety of OnabotulinumtoxinA. The golden rule is that OnabotulinumtoxinA should be administered only if the healthcare provider has made sure that the potential benefits outweigh the risk to both, the mother and the fetus. Administration of OnabotulinumtoxinA in lab mice had resulted in a decrease in fetal weight. This had been observed in rats and rabbits as well. All the administration of OnabotulinumtoxinA was given intramuscularly.

• Breastfeeding Females:

Caution and care should be taken while administering OnabotulinumtoxinA to a nursing female. This is because the majority of the drugs are excreted in human milk. Nevertheless, there are no strongly established reports of precedence of OnabotulinumtoxinA in human milk.

• Use in the Pediatric Population:

The efficacy and safety of OnabotulinumtoxinA in a patient who is below the age group of eighteen have not been established in the below-mentioned medical conditions.

• Prophylaxis of headache in cases of chronic migraine.

• Spasticity.

• Cervical dystonia.

• Strabismus.

• Blepharospasm.

• Axillary hyperhidrosis.

• Use in Geriatric Population:

There have not been heavy clinical studies to establish the performance of OnabotulinumtoxinA in senile patients. Thus it is by default taken that OnabotulinumtoxinA works the same in both adults and geriatric groups. It should be noted that the selection of the dose of OnabotulinumtoxinA should be different as per the underlying medical condition of the senile patients, which may include hepatic insufficiency, cardiac malfunctioning, drug therapy, decreased renal output, and concomitant conditions.

What Is the Mechanism of Action of OnabotulinumtoxinA?

OnabotulinumtoxinA works by blocking the neuromuscular junction and transmission with the help of binding to the acceptor sites. These sites are on the sympathetic nerve terminals or the motor nerve terminals. They enter the nerve and inhibit the release of acetylcholine. This particular inhibition takes place because the neurotoxin separates and forms a protein that is successful in releasing acetylcholine from the vesicles present in the nerve endings. Intramuscular administration of OnabotulinumtoxinA leads to incomplete denervation of the chemical agents. This results in a reduction of muscular activity that is at a particular location. The injected muscle may develop extra junctional acetylcholine and may also atrophy. There has been established evidence of reinnervation of muscle post administration of OnabotulinumtoxinA. Intradermal administration of OnabotulinumtoxinA may lead to partial denervation of the chemical factors present in the sweat glands, thus resulting in a reduced amount of sweating.

What Are the Pharmacokinetics of OnabotulinumtoxinA?

With the help of the present technology of analytics, it is not possible to determine OnabotulinumtoxinA in the peripheral blood after an intramuscular injection given at the recommended doses.

What Are the Nonclinical Toxicology Factors of OnabotulinumtoxinA?

• Carcinogenesis:

Studies in animals have not been done, and thus, the evaluation of carcinogenic factors and the carcinogenic potential of OnabotulinumtoxinA is not established.

• Mutagenesis:

There was no presence of OnabotulinumtoxinA in vitro after microbial reverse mutation assay, chromosomal aberration assay, and mammalian cell mutation assay as well as in vivo after micronucleus assays and genetic toxicology assay.

• Fertility Impairment:

Studies have shown reduced fertility in mating rats who had been injected with intermediate and high doses of OnabotulinumtoxinA. Further, there was a reduction in fertility amongst female rats at a higher dose of OnabotulinumtoxinA.

OnabotulinumtoxinA For Patients

OnabotulinumtoxinA, commonly known as Botox, is a chemical agent indicated for the treatment of chronic migraine.

Warning

OnabotulinumtoxinA has the potential to reach distant tissues and result in changes parallel to that of OnabotulinumtoxinA symptoms. The effects that are produced by OnabotulinumtoxinA are reported to come into the picture after a few hours to weeks of exposure to OnabotulinumtoxinA. Difficulty in breathing and obstruction while swallowing are the two life-threatening consequences of OnabotulinumtoxinA that have been reported. Children and adults with underlying medical conditions are highly prone to developing serious risks to OnabotulinumtoxinA, and deaths have also been reported for the same.

What Happens in a Case of Overdosage of OnabotulinumtoxinA?

Neuromuscular weakness is one of the most common aftermaths of an overdose of OnabotulinumtoxinA. The patients may need respiratory support because the respiratory system and respiratory muscles may get temporarily paralyzed by the effect of OnabotulinumtoxinA. The patient should be under constant monitoring with symptomatic treatment. An overdose may present itself immediately after injection of OnabotulinumtoxinA and not anytime later. In case there is ingestion or swallowing of OnabotulinumtoxinA, the individual should be kept under constant supervision in order to understand the signs and symptoms of paralysis and weakness of muscles.

How Is OnabotulinumtoxinA Stored?

The supply of OnabotulinumtoxinA is in a one-time use vial of fifty units, hundred units, and two hundred units. OnabotulinumtoxinA should be stored in a refrigerator between the temperatures of two degrees celsius and eight degrees celsius for around thirty-six months. OnabotulinumtoxinA must not be used after it has crossed the expiration date. After twenty-four hours of reconstitution, OnabotulinumtoxinA must be administered. The reconstituted OnabotulinumtoxinA is a colorless, clear, and free of particles unit.

What Is the Patient Counseling Information of OnabotulinumtoxinA?

The patients are advised to visit their healthcare provider in case they experience any of the following.

• Worsening headache.

• Difficulty while swallowing.

• Difficulty while speaking.

• Obstruction while breathing.

• Unusual behavior.

• Blurred vision.

• Drooping of eyelids.

• Weakness of the muscles.

• Loss of physical strength.

Conclusion

OnabotulinumtoxinA is a formula of botulinum toxin of type A. Commercially, it has been marketed as Botox. OnabotulinumtoxinA is indicated in patients suffering from chronic migraine, upper limb spasticity, cervical dystonia, axillary hyperhidrosis, blepharospasm, and strabismus. OnabotulinumtoxinA is contraindicated in patients who have a known allergy or a history of anaphylaxis to OnabotulinumtoxinA, patients suffering from upper respiratory tract disorders, patients suffering from an ongoing infection, or any other hypersensitivity. OnabotulinumtoxinA has the potential to spread to distant tissues and they too may develop the symptoms of OnabotulinumtoxinA.

The adverse effects of OnabotulinumtoxinA include drooping of the eyes, flu-like symptoms, fever, increased cough, difficulty in swallowing, obstruction in breathing, non-axillary sweating, hemorrhage, and pain at the site of injection. There are not any established results of OnabotulinumtoxinA reacting in pregnant patients or nursing females.

Nevertheless, drugs and proteins excrete in human milk and since the majority of the drugs are able to pass the fetal barrier, OnabotulinumtoxinA should be avoided in pregnant and breastfeeding females. It is advised to the patients to inform their healthcare provider as soon as possible of any reactions that may make them uncomfortable such as weakness in muscles, slurred speech, unusual behavior, blurred vision, extreme headache and difficulty while swallowing or speaking. The recommended dose and strength of OnabotulinumtoxinA is determined by the healthcare provider based on several factors. Patients must always consult a medical professional before deciding to go ahead with any kind of toxin related therapies such as OnabotulinumtoxinA in order to keep adverse effects at bay.