COMBINED THERAPIES

5% XANDROX SOLUTION

(Updated 3/29/2008)

The currently accepted state-of-the-art medical treatment for male pattern baldness is the concurrent use of high-concentration topical minoxidil, retinoic acid and daily doses of an anti-androgen such as topical spironolactone, topical azelaic acid or oral finasteride (Propecia). There have also been numerous enthusiastic reports in the popular press in regards to the effectiveness of this new approach to male pattern baldness. It is exciting to realize that balding is now a choice, rather than a fate.

Topical minoxidil is dose dependant and the higher the concentration, the more effective it is in promoting hair growth. The retinoic acid acts as a chemical 'peel' and allows for greater penetration of the scalp. Topical 5% minoxidil has been successfully combined with azelaic acid in a single solution (Xandrox) to provide simultaneous inhibition of DHT as well as stimulation to hair growth.

Since 30 September '98, REGROWTH has made available newly formulated solutions, utilizing the only two FDA approved methods for treating pattern baldness: topical minoxidil and azelaic acid, an agent that prevents enzymatic conversion of testosterone to dihydrotestosterone (DHT).

Xandrox is a proven, effective, affordable and exclusive topical solution that integrates the best pharmacologic properties of minoxidil and azelaic acid. The product is formulated both with and without retinoic acid to allow for daytime and nighttime use. Minoxidil is dissolved into the solution at a concentration of 5% to maximize its stimulus to hair growth. Azelaic acid, also at a 5% concentration, will inhibit virtually all (>98%) the 5-alpha reductase in the areas of the scalp to which it is applied, preventing any local formation of DHT. Xandrox topical solutions are dispensed in 3 oz. Bottles containing 65mL of medication and are accompanied by a calibrated medicine dropper and/or a fine mist sprayer for ease of application.

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Minoxidil 5%

Description: Minoxidil topical solution is a non-specific hair growth stimulant. Minoxidil appears as a white or off-white, odorless crystalline solid that is soluble in water to the extent of approximately 2 mg/mL, but more readily soluble in propylene glycol or ethanol. The chemical name for minoxidil is 2, 4-pyrimidinediamine, 6-(1-piperinedinyl)-3-oxide (MW= 209.25). Xandrox topical solutions contain 50 mg minoxidil per milliliter.

Clinical Pharmacology: Minoxidil topical solutions stimulate hair growth in individuals with androgenetic alopecia, expressed in males as thinning or the hair at the vertex, crown, temporal and/or frontal areas and in females usually as diffuse hair loss or thinning in the frontoparietal areas. The mechanism by which minoxidil stimulates hair growth is not known but is thought to have a direct effect on the hair follicle to sustain the anagen phase of the hair cycle. It has also been shown to have a vasodilatory effect on the scalp. Minoxidil is a direct acting peripheral arterial dilator that reduces blood pressure by decreasing peripheral vascular resistance.

In placebo controlled trials involving over 3500 male patients given topical minoxidil for 4 months (longer treatment was given after the placebo group was discontinued) and in over 300 female patients given topical minoxidil for eight months, the typical systemic effects of oral minoxidil (weight gain, edema, tachycardia, fall in blood pressure, and their more serious consequences) were not seen more frequently in patients given topical minoxidil than in those given topical placebo. The mean changes from baseline in weight, heart rate, and blood pressure in the treated and placebo groups were similar, and the number of patients experiencing significant changes, such as blood pressure decrease of 15 mmHg or more diastolic or 30 mmHg or more systolic, a heart rate increase of 15 beats/minute or more, or weight gain of at least 5 pounds, was also similar.

The failure to detect evidence of systemic effects during treatment with topical minoxidil reflects the poor absorption of topical minoxidil, which averages about 1.4% (range 0.3 to 4.5%) from normal intact scalp, and was about 2% in the hypertensive patient, whose scalps were shaved. Since it requires 20 ng /mL of serum to have any systemic effects in the human body and allowing for an average absorption rate of 1.4%, there remains a greater than 16-fold safety margin in the use of 5% topical minoxidil.

Following cessation of topical dosing of minoxidil, approximately 95% of systemically absorbed minoxidil is eliminated within four days. Minoxidil and its metabolites are excreted principally in the urine.

Indications and Usage: Xandrox topical solutions are indicated for the treatment of alopecia androgenetica in men and women. At least four months of twice daily application are usually required before evidence of hair growth can be expected. Even in patients for whom topical minoxidil does not seem effective for restoring hair loss, for most patients it will prevent further thinning and loss due to alopecia androgenetica.

Contraindications: Topical minoxidil is contraindicated in those with a hypersensitivity to any of the components of the preparation.

Warnings: Although extensive use of topical minoxidil has not revealed evidence that enough minoxidil is absorbed to have systemic effects, greater absorption or individual variability or sensitivity could theoretically cause a systemic effect. If systemic effects were to occur, patients with underlying heart disease would be at particular risk. Minoxidil could also have additive effects with other therapies in patients being treated for hypertension.

Drug Interactions: There are no known drug interactions associated with the use of a topical minoxidil solution.

Adverse Reactions: In placebo controlled trials, the rate of adverse reactions were no more common, other than dermatologic events such as irritation and allergic dermatitis.

Overdosage: There are no known cases of overdosage resulting from topical minoxidil administration. Minoxidil and its metabolites are hemodialyzable.

Azelaic acid 5%

Description: Azelaic acid is a naturally occurring saturated dicarboxylic acid with the chemical name of 1,7-heptanedicarboxylic acid and a molecular weight of 188.22. Azelaic acid is a dietary component of whole grain cereals and animal products.

Clinical Pharmacology: The exact mechanism of action of azelaic acid is not known. The antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis. Azelaic acid at high concentrations is bactericidal against Propionibacterium acnes and Staphylococcus epidermis and possesses bacteriostatic properties against a variety of aerobic microorganisms, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. In vitro, azelaic acid acted as a scavenger of oxy radicals and inhibits a variety of oxidoreductive enzymes including 5-alpha reductase.

Azelaic acid (0.1 to 3.0 mmol/l) has been shown to produce a competitive concentration dependent inhibition of 5-alpha reductase activity in homogenates of human foreskin. Azelaic acid is being studied for potential antimycotic and antiviral properties. The multiple actions of azelaic acid cause a normalization of keratinization and a decrease in the free fatty acid content of skin surface lipids.

Pharmacodynamics: Following a single application to human skin, 3 to 5% of the azelaic acid penetrates into the strateum corneum (up to 10% is present in the dermis and epidermis). There is negligible cutaneous metabolism after topical application. Approximately 4% of topically applied azelaic acid is systemically absorbed and mainly excreted unchanged in the urine. The half-life is approximately 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics. After topical treatment with azelaic acid, plasma concentration and urinary excretion are not significantly different from baseline levels.

Contraindications: Xandrox solutions are contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings: There have been isolated reports of hypopigmentation after use of azelaic acid, although there is no depigmenting effect on normal melanocytes.

Precautions: If sensitivity or severe irritation develops with the use of Xandrox, treatment should be discontinued. The most common adverse reactions occurring in approximately 1-5% of patients were pruritis, burning, stinging and tingling, usually at the start of treatment and may last 5 to 20 minutes, especially if the skin is inflamed or broken. The adverse effects commonly subside if treatment is continued. Other adverse reactions such as erythema, dryness, rash, peeling, irritation and dermatitis were reported in less than 1% of patients. The following additional adverse experiences have been rarely reported: worsening of asthma, vitilago pigmentation, hypertrichosis and reddening (signs of keratosis pilaris). Note: azelaic acid will consistently lighten hyperpigmented skin (skin that is daker than normal for a given individual) but will not typically lighten skin beyond its normal color. Rarely, patients with dark complexions may notice hypopigmentation of skin. There are no systemic adverse effects.

Considerations: Azelaic acid is normally found in the human diet and is not considered to be a carcinogenic substance. Mutagenicity studies are negative and animal studies have shown no adverse effects on fertility or reproduction. Human problems have not been reported during pregnancy.

Retinoic Acid 0.025%

Description: Tretinoin is all-trans retinoic acid. Xandrox topical solutions for nighttime use contain 0.025% retinoic acid by weight.

Clinical Pharmacology: Although the exact mechanism of action is not known, evidence suggests that retinoic acid decreases cohesiveness of follicular epithelial cells, acting on the skin as a mild chemical peel.

Indications and Usage: The routine application of Xandrox topical solutions containing retinoic acid allows for better penetration of minoxidil into the scalp. Since retinoic acid is decomposed by strong light, it is recommended that Xandrox topical solutions containing retinoic acid only be used at night.

Contraindications: Xandrox topical solutions should be discontinued if hypersensitivity to any of the ingredients is noted.

Precautions: Chronic exposure to sunlight, including sunlamps, should be minimized while using Xandrox topical solutions containing retinoic acid. Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to sunlight should exercise particular caution. Topical use may cause severe local erythema and peeling at the site of application, in which case use of Xandrox topical solutions should be less frequent or discontinued. Use on eczematous skin may cause severe irritation.

Drug Interactions: Caution should be exercised in concomitant use with medicated or abrasive soaps and cleansers, especially those containing sulfur, resorcinol or salicylic acid.

Adverse Reactions: The skin of certain sensitive patients may become excessively red, edematous, blistered or crusted. If these reactions occur, Xandrox topical solution containing retinoic acid should either be discontinued until the integrity of the skin is restored or the medication adjusted to a tolerable level. True contact allergy to retinoic acid is rarely encountered. There is heightened susceptibility to sunburn in the areas to which retinoic acid is applied. All adverse effects of retinoic acid are reversible upon discontinuation of use.

Dosage and Administration: Hair and scalp should be dry prior to topical application of Xandrox topical solutions. A total dose of 1 mL should be applied to the affected areas of the scalp twice daily. 1 mL of the Xandrox topical solution, which does not contain retinoic acid, can be alternated with 1 mL of Xandrox topical solution containing retinoic acid for nighttime use. The total daily dosage should not exceed 2 mL. Twice daily applications for four months or longer may be required before evidence of hair growth is observed. Onset and degree of hair growth is variable among patients. Twice daily applications appear necessary for additional or continued hair regrowth. Reports indicate that regrown hair and the balding process return to their untreated state three to four months following cessation of topical minoxidil.

How Supplied: Xandrox topical solutions are supplied in 3 oz. Bottles and contain 65 mL of clear, colorless to light yellow, odorless solutions with 5% minoxidil, 5% azelaic acid, in a base of ethyl alcohol, propylene glycol, distilled water and tocopherol (vitamin E). Xandrox topical solutions for nighttime use also contain 0.025% retinoic acid.

Store at controlled room temperature at 59 to 86 degrees Fahrenheit (15 to 30 degrees Centigrade).

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Auf Deutsch

Xandrox ist das stärkste Mittel zur Behandlung der androgenetischer Alopezie. Xandrox besteht zum größten Teil aus einem Mittel, das es schon seit Jahren gibt: Minoxidil, und zwar in einer Konzentration von 5% bis 15%. Die anderen Komponenten sind: Azeleic Acid 5%, und für die Nacht-Behandlung zusätzlich Retin-A .025%. Azeleic Acid wurde bisher zur Behandlung von Akne oder anderen Hautirritationen verwendet, soll aber auch in klinischen Tests bewiesen haben, daß es DHT in der Kopfhaut blockieren kann. DHT (Dihydrotestosteron) ist die Hauptursache für genetisch bedingten Haarausfall.

Retin-A .025% dient hauptsächlich dazu, die Kopfhaut für das Minoxidil vorzubereiten, sodaß es besser in die Kopfhaut eindringen kann.Xandrox ist also eine 5% - 15% Minoxidil-Lösung mit Helfer-Komponenten, die es der Lösung einfacher machen sollte, Wirkung in der Kopfhaut zu erzielen. Somit sind die Erwartungen entsprechend höher, als wenn man nur ein Mittel alleine verwendet.

Bald fangen wir an, eine 15% Xandrox Lösung anzubieten, die Finasteride und Azelaic Säure enthält.

E-Mail: REGROWTH@minoxidil.com