Strong Treatment for AGA

Strong Treatment for AGA

Hada no clinic’s AGA strong treatment is to prevent hair loss with dutasteride (oral medication), which is more effective than finasteride, and to promote hair growth with minoxidil oral medication. In addition, NINASOL shampoo, which suppresses male hormones, is recommended.

For frontal type alopecia (including the M-shaped area) and young patients whose hair loss is progressing quickly, the standard treatment is not expected to be very effective, so strong treatment may be used from the beginning according to the patient’s wishes.

Minoxidil tablets, ketoconazole (Ninazol shampoo and lotion), dutasteride AV and finasteride (overseas products) are unapproved drugs for AGA in Japan and are therefore not covered by the Pharmaceutical Side Effects Relief Scheme.

Cases of treatment

Dutasteride 0.5mg AV + Minoxidil tablet 5mg + Ninazol Shampoo

In the case of strong therapy, the presence of underlying medical conditions is tested and confirmed at the first visit, followed by blood pressure, blood tests (including heart failure markers), ECGs and urine tests every six months to prevent side effects as far as possible.

Dutasteride

Dutasteride has been used abroad since 2001 as a treatment for benign prostatic hyperplasia and was known to have the side effect of ‘excessive hair growth on the head’, which was then applied to AGA treatment as an indication.

In Japan, Zagallo was approved in 2016 for the treatment of male pattern baldness; a generic version of Zagallo, dutasteride ZA, has been available since October 2020.

Dutasteride suppresses DHT production by inhibiting type I 5α-reductase and type II 5α-reductase enzymes, which are necessary for the production of DHT (dihydrotestosterone), the cause of AGA. The average number of hair growth at 12 and 24 weeks was reported to be approximately 1.6 times greater for dutasteride 0.5mg compared to finasteride 1mg, and hair thickness was 1.45 times greater as well.

For specific treatment results and effects, see also the AGA blog ‘Dutasteride Effects and Side Effects 1‘ and ‘Dutasteride Effects and Side Effects 2‘.

Precautions of dutasteride treatment

1. It is not indicated for hair loss under 20 years old, female alopecia, alopecia areata, and alopecia due to anticancer drugs, etc.
2. Pregnant women, women who may become pregnant or women who are breastfeeding cannot use dutasteride.
3. Although the possibility of effects to fetus by dutasteride is very low, we still recommend contraception should be used while taking finasteride and until 6 months after discontinuation of the treatment to ensure that transfer of finasteride to semen has been completely eliminated.
4. Please avoid blood donation during taking dutasteride until 6 months after discontinuation of the treatment.
5. It usually takes at least 6 months to see the effect of dutasteride treatment.
6. If dutasteride is discontinued, the treatment effect will be lost and the symptoms of AGA will gradually progress again.
7. Please be sure to inform your doctor that you are taking dutasteride when undergoing prostate cancer screening. Dutasteride lowers PSA levels by approximately 50% and should be twice the measured PSA level.
8. Initial hair loss may occur during the first month of dutasteride treatment.

	>1%	Less than 1%	Frequency unknown
Allergy		Skin rash	Urticaria, allergic reaction, pruritus, localized edema, angioedema
Psyciatric, neurological		Headache, depressed mood	Floating dizziness, taste disorder
Reproductive system and breast disorders	Sexual dysfunction (decrease sexual desire, erectile dysfunction, ejaculation disorder)	Gynecomastia, breast and nipple pain, breast discomfort	Testicular pain, testicular swelling
Skin			Hair loss(mainly body hair loss), excessive hair growth
digestive organs		Abdominal discomfort	Abdominal pain、 diarrhea
Others			Abnormal liver function, jaundice, fatigue, increased creatine kinase in blood

1. The frequency of adverse reactions that have been reported spontaneously or have been observed only overseas is considered to be unknown.
2. Few studies reported persistent side effects even after discontinuation of dutasteride.
3. It has been reported as a serious adverse reaction, and blood tests are recommended every 6-12 months. If symptoms such as yellowing of the whites of the eyes, lethargy, fever, rash, or nausea occur, please consult a doctor immediately.

• In a 4-year global study (including 57 Japanese patients) of 8231 predominantly Caucasian men aged 50-75 years (biopsy-negative prostate cancer and PSA 2.5-10.0ng⁄mL), the incidence of prostate cancer with Modified Gleason Score 8-10 was reported to be higher in the dutasteride group (1.0%) than in the placebo group (0.5%) (relative risk 2.06). (※Reference: In general, the cumulative lifetime risk of prostate cancer is 9.7%, or about 1 in 10 people, according to statistics in 2015.)
• Of 557 patients (including 120 Japanese), 95 (17.1%) reported adverse reactions including abnormal laboratory tests. The most common adverse reactions were erectile dysfunction in 24 cases (4.3%), decreased sexual desire in 22 cases (3.9%), and decreased semen volume in 7 cases (1.3%). Of 120 Japanese patients, 14 (11.7%) reported adverse reactions including abnormal laboratory tests, the most common were decreased desire in 7 (5.8%), erectile dysfunction in 6 (5.0%), and ejaculation disorder in 2 (1.7%) patients (at the time of approval).
• In a long-term administration study in Japan, adverse reactions including abnormal laboratory tests were reported in 20 (16.7%) of 120 total patients treated with dutasteride. The most common adverse reactions were erectile dysfunction in 13 patients (10.8%), decreased sexual desire in 10 patients (8.3%), and ejaculation disorder in 5 patients (4.2%) (at the time of approval).
• The mean percentage of reduction in total sperm count, semen volume, and sperm motility compared with pre-treatment values (adjusted for change from pre-treatment values in the placebo group) at week 52 were 23%, 26%, and 18%, respectively, with no effect on sperm concentration or morphology. The mean percentage decrease in total sperm count in the dutasteride group remained 23% after 24 weeks of follow-up. However, the mean values of all semen parameters were within normal limits and did not reach the pre-specified clinically significant variation (30%) at either evaluation time point. In addition, two patients in the dutasteride group showed a decrease in sperm count of more than 90% from pre-treatment values at ｗeek 52, but the decrease was mild by ｗeek 24 of follow-up. The clinical significance of the effect of dutasteride on semen characteristics on the fertility of individual patients is unknown.
• Male breast cancer has been reported in post-marketing patients treated with this drug. The association between dutasteride and the development of male breast cancer is unknown. Of the 3 breast cancer cases reported in overseas clinical studies (4325 cases) conducted over 2 to 4 years, 2 cases were reported in patients who received dutasteride (exposure periods of 10 weeks and 11 months) and 1 case was reported in patients who received placebo only. There have been no reports in Japanese clinical trials.

No interactions between dutasteride and other drugs have been reported; concomitant use with drugs that inhibit CYP3A4 (e.g., ritonavir, ketoconazole, verapamil, diltiazem) may decrease dutasteride metabolism (increase blood levels).

Dutasteride AV is a generic drug for Avolve (for treatment of benign prostatic hyperplasia), and Dutasteride ZA is a generic drug for Zagallo (for treatment of AGA). Both are products of Towa Pharmaceutical and have the same active ingredients and treatment effects. However, Dutasteride AV is an off-label prescription for AGA and is not covered by Relief Systems for Adverse Drug Reactions (a guarantee from the pharmaceutical company in the event of serious side effects after proper use of medications) if there are any severe side effects that occur after treatment.

Fees

	Price (Tax included)
Dutasteride 0.5mg AV	30 tablets ¥5,280
Dutasteride 0.5mg ZA	30 tablets ¥8,580
Blood tests (only when necessary)	¥2,948

• A consultation fee (¥3,850 for initial visit, ¥1,650 for repeated visit) will be charged for prescriptions.
• Since dutasteride is a pharmaceutical product, please note that we do not accept returns or refunds after prescription, even in the case of side effects occurrence, etc.
• We recommend a blood test every 6 to 12 months, but it is not necessary if you have already had a blood test from other hospitals or routine health check.

Minoxidil Tablets

Precautions for Minoxidil tablets treatment

1. People with high or low blood pressure, arrhythmia, or heart disease should always consult a doctor.
2. People with a history of myocardial infarction or angina pectoris, or with pheochromocytoma cannot take Minoxidil tablets
3. People who had allergy to Minoxidil cannot take Minoxidil tablets.
4. People under 20 years or over 65 years of age must consult a doctor.
5. Pregnant women, women who may be pregnant, and women who are breastfeeding cannot take Minoxidil. Men should also use contraception while taking the drug. Also, please stop taking Minoxidil one month before you plan to become pregnant.
6. It is usually takes at least 6 months to see treatment results.
7. If you stop taking the drug, the effect will be lost and the symptoms of AGA will progress again.
8. Do not donate blood while taking Minoxidil. It is safe for blood donation one month after discontinuation of the drug.
9. Initial hair loss may occur during the first month of treatment.
10. Keep out of reach of children and pets. If a dog or cat accidentally take the medicine, take it to an veterinary clinic for help immediately.

Frequent side effects

Hypertrichosis, swelling, palpitations, headache

Serious side effects

Heart failure, angina pectoris, myocardial infarction, cardiac hypertrophy, arrhythmia, pericarditis, cardiac tamponade, nephrogenic systemic fibrosis (a disease that causes renal failure, thickening of skin, joint contracture and physical dysfunction), hyperkalemia, liver dysfunction, multi-organ failure, Stevens-Johnson syndrome

Although very rare, if symptoms such as decreased blood pressure, fainting, edema of the face, lips, or neck, rash, difficulty breathing, or convulsions occur due to an excessive immune reaction (anaphylaxis), please call an ambulance immediately and receive treatment at a hospital.

Other side effects

Rash, redness of face, low blood pressure, reflex hypertension, acne, urticaria, hot flashes, dizziness, lightheadedness

*Because of the wide variety of side effects, electrocardiogram, blood test including pro-BNP (a marker of heart failure), urinalysis, and blood pressure measurement at the initial visit and every 6 months thereafter are necessary.

*If any of the above symptoms or abnormalities are observed, please be sure to consult your doctor as discontinuation of treatment may be necessary.

When combined with the sympatholytic agents such as guanethidine, hydrochlorothiazide, and guanadrel, and the muscle relaxant tizanidine, the side effects of postural hypotension, dizziness, and decreased heart rate may be enhanced and syncope may occur. Other drugs for high blood pressure (antihypertensive drugs), diuretics, and erectile dysfunction (ED) drugs such as Viagra, Levitra, and Cialis may also increase the effects of lowering blood pressure, so please consult your doctor.

Allow an interval of at least 4 hours between taking Minoxidil tablets and ED medications; if you want to take Minoxidil tablets after ED medications, please set an interval of at least 4 hours for sildenafil (Viagra) and vardenafil (Levitra) and at least 14 hours for tadalafil (Cialis) because of its longer duration of action. After taking the medicine, please carefully monitor for symptoms such as dizziness, discomfort, fainting, palpitations, etc. If any symptoms occur, discontinue immediately and consult your doctor.

Drugs other than sympatholytic and antihypertensive agents that may interact with Minoxidil include

• Acetazolamide (Diamox for Glaucoma)
• Alfuzosin (Alfusin α-blocker, for prostatic hypertrophy)
• Diazoxide (for hyperinsulinemia)
• Methylphenidate (for narcolepsy)
• Epoprostenol (for pulmonary hypertension)
• MAO inhibitor (for Parkinson’s disease)
• Pentoxifylline (for arteriosclerosis obliterans)
• Phosphodiesterase 5 inhibitor ( for benign prostatic hyperplasia)
• Quinine (therapeutic agent for malaria)
• Rituximab (anticancer drug)
• Antipyretic analgesics such as diclofenac (Voltaren), ibuprofen (Brufen), and naproxen (Naixan) may cause sodium and water retention and increase blood pressure. If swelling or blood pressure changes are observed, please refrain from taking Minoxidil tablets.

There have been reports of increased hypotension with other concomitant medications such as diphenhydramine hydrochloride (antihistamine, Restamine) and alprazolam (anti-anxiety medications such as Solanax).

Fees

	Price (Tax included)
Minoxidil tablet 2.5mg	30 tablets ¥4,290
Minoxidil tablet 5mg	30 tablets ¥4,290
Minoxidil tablet 10mg	30 tablets ¥5,280

• A consultation fee (¥3,850 for initial visit, ¥1,650 for repeated visit) will be charged for prescriptions.
• Blood pressure and blood tests (¥5,148), electrocardiogram (¥2,706), and urinalysis (¥1,848) are required at the initial visit and every 6 months thereafter.
• A maximum of six-month prescription is available.
• Since Minoxidil tablet is a pharmaceutical product, please note that we do not accept returns or refunds after prescription, even in the case of side effects occurrence, etc.

Ketoconazole 2% Topical Preparation

Ninazol shampoo contains 2% ketoconazole, an antifungal medicine. Ketoconazole has been reported to reduce dandruff and sebum, as well as inhibit male hormones (DHT), which cause AGA.

Although overseas guidelines have a level of recommendation of C1 (may be used), it has been shown to be effective in several trials with AGA patients and is recommended as an adjunctive hair growth treatment.

Use ketoconazole lotion if you do not like the smell of shampoo or if you do not like the way your hair creaks.

How to use Ketoconazole 2% Topical Preparation

Ninazol Shampoo

After wetting the hair, take a 100 yen coin ~ 500 yen coin sized amount onto the palm of your hand. Lather lightly in the palm of your hand, apply to the thinning hair area and surrounding area and massage lightly with your fingers. You may also apply it to the entire scalp. Then leave on for five minutes and rinse well with lukewarm water.

Use three times a week is sufficient, but if you are concerned about scalp dirt, you can use it daily. In such cases, use the shampoo as you would a normal shampoo, without leaving it on for five minutes.

The right amount of NINASOL shampoo is enough to make a light lather when applied to the hair; the amount to be used at one time varies from person to person depending on the amount of hair and sebum on the head, so increase or decrease accordingly.

Each bottle lasts approximately 2 months.

Ketoconazole Lotion

Apply approximately 0.5 mL (half a 10 yen coin) twice daily to the scalp and massage gently.

If you are using minoxidil lotion, we recommend using it before minoxidil lotion. In fact, the effect will be the same whichever comes first, but if you use minoxidil first, more of the minoxidil ingredients will stick to your hair, causing it to become powdery and dry.

Each bottle lasts approximately 7-10 days.

Who may not eligible for using Ketoconazole 2% Topical Preparation

• Those who are allergic to Ketoconazole
• Those who are pregnant or breastfeeding

Side effects are rare, but include:

• Skin side effects (frequency unknown)
  skin burning, rash, dermabrasion, sticky feeling of skin, urticaria, erosion, cracks, pain, irritation, pruritus, contact dermatitis, erythema, blisters
• Systemic disorders and side effects of administration locally (frequency unknown)
  Application site reactions (bleeding, discomfort, dryness, inflammation, confusion, edema)
• Side effects of the immune system (frequency unknown)
  hypersensitivity
• Other side effects (frequency unknown)
  urine protein positive

If symptoms of side effects appear, discontinue use and consult a doctor.

Fees

	Price (Tax included)
Ninazol Shampoo 100ml	1 bottle ¥2,178
Ketoconazole Lotion 10g	1 bottle ¥660

AGA Strong Treatment Fees (tax included)

Click to see.

Example of fees for an initial visit [2 months’ worth]

Initial consultation fee	¥3,850
Finasteride 1mg (Overseas Products) [60 tablets]	¥5,940
Minoxidil Tablets 5mg [60 tablets]	¥8,580
Ninazol Shampoo 100ml [1 bottle]	¥2,178
Examinations	Blood test ¥5,148 ECG test ¥2,706 Urine test ¥1,848
Total fees	¥30,250

Example of fees for an repeated visit [4 months’ worth]

repeated consultation fee	¥1,650
Finasteride 1mg (Overseas Products) [120 tablets]	¥11,880
Minoxidil Tablets 5mg [120 tablets]	¥17,160
Ninazol Shampoo 100ml [2 bottles]	¥4,356
Total fees	¥35,046

Example of fees for an initial visit [2 months’ worth]

Initial consultation fee	¥3,850
Dutasteride 0.5mg AV [60 tablets]	¥10,560
Minoxidil Tablets 5mg [60 tablets]	¥8,580
Ninazol Shampoo 100ml [1 bottle]	¥2,178
Examinations	Blood test ¥5,148 ECG test ¥2,706 Urine test ¥1,848
Total fees	¥34,870

Example of fees for an repeated visit [4 months’ worth]

repeated consultation fee	¥1,650
Dutasteride 0.5mg AV [120 tablets]	¥21,120
Minoxidil Tablets 5mg [120 tablets]	¥17,160
Ninazol Shampoo 100ml [2 bottles]	¥4,356
Total fees	¥44,286

• A consultation fee is charged for prescribing oral medication. Re-visits can also be made using ‘telemedicine‘, but patients taking oral minoxidil tablets should have an examination every six months.
• Medicine prices vary depending on the type of drug (domestic or foreign) and dosage.
• If you are taking minoxidil tablets, our clinic always performs various tests including a marker of heart failure (pro-BNP) every six months to ensure that no serious side effects are occurring.
• At the first visit, we prescribe a two-month supply to observe any side effects, followed by a four-month supply if there are no problems at the second visit, and then once every three months thereafter. On request, we can prescribe up to a six-month supply of medication.

Convenient telemedicine

Our clinic is the first in the country to prescribe AGA medication via telemedicine. Initial consultations require a face-to-face consultation, but for those who live too far away to visit the clinic or are too busy with work to spare the time, we offer online consultations and prescriptions, and deliver the medication to your home.

To use remote consultation, you need to fill in the ‘Agreement for Telemedicine’. For more information, please see ‘Telemedicine‘ and contact our reception if you wish to use this service.