Botulinum toxin treatment– Botulinum Toxin Treatment –

TOC

Botulinum toxin injection

The bacterium Clostridium botulinum is naturally found in environments like soil and water. The treatment using the neurotoxin produced by this bacterium, known as “Botulinum toxin,” is called Botulinum toxin injection.

This toxin has the ability to paralyze muscles and inhibit the function of sweat and oil glands. This characteristic is harnessed for the treatment of specific conditions and symptoms.

Botulinum Toxin Treatment at HADA NO CLINIC

In our clinic, we primarily use Botulinum toxin treatment for the following conditions and symptoms. For more details on each treatment, please click on the respective pages.

Botulinum Toxin Preparations

While BOTOX® is a well-known brand in botulinum toxin preparations, CORETOX® is a new formulation derived from the same type A botulinum toxin as BOTOX®. BOTOX® is trademarked by the American company Allergan, while CORETOX® is trademarked by the South Korean company Meditox.¹

CORETOX

CORETOX uses the same strain of Clostridium botulinum (Hall Hyper strain) as BOTOX Vista.

Conventional botulinum toxin formulations typically contain “human serum albumin” and “animal-derived ingredients.”

CORETOX does not contain human serum albumin or animal-derived ingredients. Furthermore, the risk of antibody production (resistance) is reduced by removing “complex proteins.” It is an approved drug by the South Korean MFDS (formerly KFDA).³

BOTOX Vista

BOTOX Vista is currently approved as a wrinkle treatment in over 70 countries worldwide, and it is a well-established medication with a proven track record of safety and effectiveness.

In Japan, it is also approved by the Ministry of Health, Labour and Welfare for the treatment of wrinkles around the eyes and between the eyebrows.²

※We have been offering both CORETOX and BOTOX Vista, but we have received more requests for CORETOX. As a result, we currently do not have BOTOX Vista in stock.

Comparison between Coretox and Botox Vista

	CORETOX	BOTOX Vista
Strain	Hall Hyper Strain	Hall Hyper Strain
Domestic Approval	No^※	Yes^※
Human Serum Albumin	Not contained	Contained
Animal-Derived Ingredients	Not contained	Contained
Complex Proteins	Removed	Contained

※BOTOX Vista is approved for use on wrinkles between the eyebrows and around the eyes. It is not approved for other uses and is not covered by the Pharmaceutical Products Side Effect Relief System. CORETOX is not covered by the Pharmaceutical Products Side Effect Relief System for any use.

If you would like to learn more about the types of botulinum toxin preparations in the field of cosmetic medicine, please check out the following article (in Japanese).

Needle

We use the finest micro-injection needles, specifically the 34G needle with a diameter of 0.18mm, at our clinic (excluding some treatment areas).

By using the thinnest needles possible, we aim to minimize discomfort and the frequency of bruising.

Individuals who cannot undergo treatment

Those with systemic neuromuscular junction disorders or severe muscle weakness (such as Myasthenia Gravis, Lambert-Eaton syndrome, Amyotrophic Lateral Sclerosis, etc.).
Pregnant, breastfeeding, or actively trying to conceive.
Those with a history of allergy to previous Botulinum toxin therapy.
Those with a known allergy to Polysorbate (an additive).
Individuals with chronic respiratory disorders.
Those with narrow-angle or angle-closure glaucoma, or its predisposing factors (e.g., narrow angles).
Individuals with difficulty swallowing.
Those with a history of seizures or epileptic episodes.

Potential side effects of botulinum toxin injections

Common Side Effects

1. Redness, swelling, pain, and warmth at the injection site.: These symptoms typically improve within several hours to a day.
2. Bruising: This can occasionally occur and may take 1 to 2 weeks to resolve.
3. Headache: Occurs in 1 to 5% of cases. It is usually mild and tends to subside within a few hours to a few days.

Risks depending on treatment area

1. Forehead and Glabella (Between the eyebrows):: Possible eyelid or eyebrow drooping, feeling of heaviness in the eyes, difficulty opening the eyes. Occasionally, the width of the double eyelid may narrow or change. Improvement is gradual over approximately four weeks.With injections to the glabella, there is a possibility of widening the spacing between the eyebrows.
We do not recommend injections to the forehead for individuals aged 60 and above.
2. Crow’s Feet (Outer corners of the eyes):: Very rare, but reported cases of eyebrow elevation (outer eyebrow lift) and dry eyes.
3. Bunny Lines (Nose wrinkles):: Very rare, but reported cases of double vision and tearing.
4. Gummy Smile:: Philtrum (area between nose and upper lip) may elongate, and corners of the mouth may become asymmetric. If asymmetry occurs, additional corrective injections will be administered on the raised side.
5. Laugh Lines (Cheeks):: Smiles may appear unnatural or become asymmetrical. Improvement typically occurs within 2 to 4 weeks.
6. Vertical Lip Lines and Lip Flip:: Difficulty in activities like puckering (drinking with a straw, whistling, saying “papipupepo”) may occur. Rarely, sensations of discomfort or numbness in the lips may be felt. Improvement usually occurs within four weeks.
7.Chin:: Difficulty in closing the mouth, elongation of the jaw, and distortion of the mouth during laughter may occur. Objects may be more easily caught between the lower lip and teeth, and biting of the lower lip may become more frequent.
8. Mouth Corners:: Asymmetry of mouth corners and distortion of the mouth during laughter may occur. Improvement typically occurs within 2 to 4 weeks.
9. Platysmal Bands:: Although extremely rare, there may be side effects such as sagging of the central neck muscles, affecting speech and swallowing function.
10. Masseter (Jawline):: It’s not recommended for individuals in their 40s or older as when the jawline disappears, it can lead to sagging skin and sunken cheeks. In some cases, certain muscles may compensate by bulging, and in such instances, corrective injections will be administered.
11.Shoulder and Calf:: Muscular soreness, sagging, difficulty in exerting force, unsteadiness, and tangling may occur, but typically improve within 2 to 3 weeks. There is a possibility of reduced motor ability. Very rarely, nerve disorders, numbness, and weakness may occur.
12. Hay Fever:: Theoretically, a transient impact on smell cannot be ruled out, but it is rare in clinical practice.
13. Hyperhidrosis (Excessive Sweating):: In exchange for reduced sweating in the treatment area, there may be increased sweating from other areas (compensatory sweating). For hands and feet, transient feelings of weakness, difficulty in grasping objects, difficulty in fine motor tasks, muscle pain, and numbness may occur.

Very rare but serious side effects

1. Anaphylactic Shock: Severe allergic reactions leading to difficulty in breathing, facial flushing, vascular swelling, rash, and a drop in blood pressure.
2. Visual Impairment: Difficulty in closing the eyes may lead to dryness and corneal damage.
3. Swallowing and Respiratory Impairment: Injections in the neck muscles may result in swallowing difficulties, changes in voice quality, and respiratory issues.
4. Spasms: Seizures or recurrent spasms may occur.

Post-injection precautions

For women who may become pregnant, please use contraception until after two menstrual cycles have occurred following the injection. For men, it is advised to use contraception for at least three months after receiving the Coretox injection.
Avoid rubbing, massaging, or applying pressure to the injection site.
After the injection, deliberately move the facial muscles in the treatment area to create some wrinkles (within 3 hours, and it’s fine to do it at a comfortable level whenever you notice).
Refrain from taking baths, using saunas, or engaging in vigorous exercise on the same day. However, showering and light makeup application are allowed on the same day.
If there is swelling, redness, or bruising at the injection site, please refrain from consuming alcohol or engaging in physical activity on that day.
Please avoid donating blood for one week after the injection.

Frequently Asked Questions about Botulinum Toxin Injections

General Questions

Which is better, Coretox or Botox Vista?

CORETOX

Coretox is produced from the same strain as Botox Vista. It is a relatively new formulation that lacks complex proteins, as well as human serum albumin and animal-derived substances.

For individuals undergoing repeated treatments or requiring higher doses for conditions such as hyperhidrosis or jawline treatments, we recommend Coretox, which is less likely to trigger antibody production.

BOTOX Vista

Botox Vista is an approved medication in Japan (specifically for wrinkles between the eyebrows and at the corners of the eyes) and has a well-established history. If domestic approval is a critical factor for you, we recommend Botox Vista.

*Currently, due to a higher demand for Coretox, we do not have stock of Botox Vista available.

How long does the effect of Botulinum Toxin injections last?

For wrinkles, the effect usually lasts around 3 to 4 months. For excessive sweating, it lasts about 5 to 6 months, and for stuffy nose due to pollen allergies, it lasts approximately 2 to 3 weeks.

Please keep in mind that the duration of the effect can vary from person to person.

Are there cases where Botulinum Toxin doesn’t work?

Botulinum Toxin injections are a treatment that works for most people when administered correctly. If it doesn’t seem effective, the following reasons might be considered:

Issues on the Medical Side

Insufficient dosage
If the dosage is too low, it can make the treatment less effective.
Incorrect injection site
If the injection isn’t made in the appropriate muscle responsible for the wrinkle or if the injection depth isn’t correct, it can reduce the effectiveness.
Use of weakened potency medication
If the formulation isn’t prepared, stored, or managed properly, it can result in diminished effectiveness.

Patient-related Issues

Low sensitivity to Botulinum Toxin (Primary resistance)
When the treatment doesn’t show results from the beginning, despite being administered correctly, it’s referred to as primary resistance. This occurs due to a low sensitivity to Botulinum Toxin, and it may require adjusting the dosage during touch-ups.
Production of antibodies against Botulinum Toxin (Secondary resistance)
If the treatment initially showed effects but the effectiveness diminishes over time, it’s called secondary resistance. This is caused by the development of antibodies against the complex proteins or Botulinum Toxin contained in the formulation.

Does the effectiveness diminish when antibodies are formed?

When neutralizing antibodies against Botulinum Toxin develop in the body, the effectiveness of the injection can be reduced⁷. However, it doesn’t completely nullify the effects. Some level of effectiveness has been reported in patients with these neutralizing antibodies^5,7.

Even if neutralizing antibodies are present, adjusting the dosage or changing the formulation can still yield some level of effectiveness. However, if it remains ineffective, treatment may be administered with longer intervals (over 2 years).

While extremely rare, there are cases where treatment may eventually need to be discontinued.

How can antibody production be prevented?

There have been reports correlating four risk factors with the production of antibodies against Botulinum Toxin formulations⁷.

Higher dosage per administration (200 units or more)
Multiple administrations
Short intervals between administrations
High cumulative dosage

Products like Coretox or Zeomin (Bocouture), which have removed complex proteins, have been reported to have lower antigenicity and a reduced likelihood of antibody production compared to conventional ones⁶. However, this information is based on findings from small-scale clinical trials and lacks definitive evidence.

For those who are concerned, it’s advisable to either choose a formulation that is less likely to produce antibodies or wait at least three months before receiving injections of 50 units or more.

What is the likelihood of developing antibodies from Botulinum Toxin injections?

According to a meta-analysis on Botulinum Toxin antibodies based on overseas data, the positive antibody rate at some point after injection is 0.28% (less than 3 out of 1000) for wrinkles between the eyebrows, and 0.46% (less than 5 out of 1000) for hyperhidrosis⁹.

Can you check if antibodies have been formed?

At present, it appears that measuring neutralizing antibodies against Botulinum Toxin is not possible domestically*.

*As of February 2021, confirmed with Allergan Japan Corporation.

Is it not possible for those aged 65 and above to receive treatment?

The package insert for Botox Vista states that “effectiveness is lower and adverse event rates are higher in elderly individuals aged 65 and above, so it is not recommended”². However, as long as the treatment is administered with the appropriate dosage and technique, it can be safely performed. Therefore, our clinic does not have specific age restrictions in place.

Is it okay to receive different types of Botulinum Toxin injections?

According to the package insert for Botox Vista, patients currently undergoing treatment with another Botulinum Toxin formulation are advised not to receive treatment with it². This is due to the potential interactions and lack of established safety between different formulations, which could carry a risk of enhanced effects.

However, in practice, there is no evidence suggesting that adverse effects are exacerbated by using different Botulinum Toxin formulations. If you are concerned, it is recommended to wait at least three months before switching to a different formulation.

Questions after injection

Is there any downtime?

Since we use an ultra-fine needle for the injection, the needle punctures are hardly noticeable. The injected area may become slightly red, but this typically subsides within 30 minutes to a few hours.

On rare occasions, there might be some bruising, which can take about 1 to 2 weeks to fully fade.

Can I apply makeup right away?

If there is no swelling or redness at the injection site, you can apply makeup without any issues. However, please avoid rubbing, massaging, or applying pressure to the injection site.

Is it necessary to apply tape?

Since there is very little to no bleeding, tape is not necessary.

Is it okay to move the facial muscles after receiving injections for wrinkles?

It’s perfectly fine to move your facial muscles right after the injection.

In fact, it has been reported that moving the muscles may increase the release of a neurotransmitter called acetylcholine, which can enhance the absorption of Botulinum Toxin into the moved muscles, potentially increasing its effectiveness⁸.

In our clinic, we recommend deliberately moving the facial muscles in the treatment area to create some wrinkles within three hours after the Botulinum Toxin injection.

When can I take a bath or use a sauna after the injection?

Some clinics may prohibit bathing or sauna use due to the sensitivity of Botulinum Toxin formulations to heat. However, since the toxin is exposed to body temperature immediately after injection, it’s unlikely that bathing or using a sauna afterwards would significantly alter its effectiveness.

The half-life of Botulinum Toxin is approximately 10 hours, and after 24 hours, only about 5% is detectable within the muscle². If you’re concerned, it’s recommended to wait at least 24 hours before taking a bath or using a sauna.

In our clinic, we recommend refraining from bathing or using a sauna on the same day for the protection of the treated area. However, you can take a shower on the same day.

Can I drink alcohol after the injection?

If there is no swelling, redness, or bruising at the injection site, it is perfectly fine to consume alcohol on the same day as the Botulinum Toxin injection.

Is it okay to exercise after the injection?

If there is swelling, redness, or bruising at the injection site, it is recommended to refrain from exercising on the same day. For the treatment of hyperhidrosis, please avoid exercise on the day of treatment to minimize sweating.

If none of the above applies, light exercise is perfectly fine. However, intense exercise should be postponed until the following day or later.

Is it possible to donate blood?

After receiving a Botulinum Toxin injection, please wait for at least one week before donating blood.

List of references/websites

Allergan, “BOTOX onabotulinumtoxinA injection” アクセス 2020.10.23
アラガン・ジャパン, “医療用医薬品：ボトックスビスタ” 添付文書情報2020年8月改訂
Medytox, “Coretox“　http://www.medytox.com/page/coretox アクセス 2020.11.21
株式会社エムエムアンドニーク, “UNIEVER注射針・注射筒” https://www.mm-japan.co.jp/product/micro_injection_needle.html アクセス 2020.11.21
Oliver Lange, “Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing?” Clin Neuropharmacol. Jul-Aug 2009;32(4):213-8. doi:10.1097/WNF.0b013e3181914d0a. PMID: 19620852
Dirk Dressler, “Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity” J Neural Transm (Vienna). 2018 Oct;125(10):1481-1486. doi: 10.1007/s00702-018-1911-3. Epub 2018 Jul 31. PMID: 30066275
Margherita Fabbri, “Neutralizing Antibody and Botulinum Toxin Therapy: A Systematic Review and Meta-analysis” Neurotox Res. 2016 Jan;29(1):105-17. doi: 10.1007/s12640-015-9565-5. PMID: 26467676
君浦隆ノ介, “脳卒中後の痙縮に対する治療(1) チーム医療として取り組むボツリヌス治療” 運動と医学の出版社発行年：2017
Markus Naumann, “Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications” Mov Disord. 2010 Oct 15;25(13):2211-8. doi: 10.1002/mds.23254. PMID: 20737546