Topical Finasteride vs Oral Finasteride

Finasteride is one of two FDA-approved treatments for androgenic alopecia. Initially originating as a chemotherapeutic agent in the 1940s, MK-906 (presently known as Finasteride) was later on used to treat benign prostate hyperplasia owing to its diminishing effect on dihydrotestosterone levels.  In 1997, it was approved by FDA for treating androgenic alopecia in males (Gupta et al., 2022). It is currently available in oral as well as topical dosage forms i.e. “Propecia”, a tablet-based dosage form with a dose of 1 mg once daily and “Keeps” and “Xyon” both topical sprays, are available on the market.

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How Does Finasteride Work?

The drug helps to treat light to moderate hair loss in the vertex and anterior mid-scalp areas, often known as the “crown area”. Finasteride exhibits its primary mode of action by suppressing the 5-alpha-reductase enzyme, which transforms testosterone into dihydrotestosterone (DHT). This helps to keep the hair-loss prone follicles safe from the androgenic action (Libecco and Bergfeld, 2004). This ultimately increases the number of terminal hairs in the anagen phase (active hair growth phase) by lowering the quantity of DHT in the scalp, which often mitigates hair loss and in some individuals can spur hair regrowth. A flow scheme of its mechanism of action can be seen in the figure below:

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Oral Finasteride: Weighing the Risks

A decrease in libido, gynecomastia, erectile dysfunction, ejaculation issues, and mood abnormalities are significant side effects which have been reported in small numbers with long-term use of oral finasteride. In a study conducted on males suffering from androgenic alopecia, these side effects persisted for a period of at least 3 months (Irwig, 2012). This eventually leads to the failure of therapy specifically in males. To counter these issues, several topical dosage forms have been developed that bypass the systemic circulation and result in decreased treatment-based side effects.

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Topical vs. Oral: Comparing Finasteride Formulations

The mode of action is the same for finasteride whether it is administered orally or topically. The difference is observed among several factors, including the drug's side effects, systemic absorption and overall efficacy. In one research study involving clinical trials-III, the systemic exposure and overall safety profile of topical finasteride were compared to those of oral finasteride, and its efficacy and safety were assessed against placebo. The total number of subjects assessed was 458 and all were males. Findings regarding efficacy showed a significant increase in hair count i.e. targeted hair count’s mean change was observed as 21.1 for topical finasteride and 20.2 for oral finasteride, meaning no significant difference was observed in the efficacy of both. The adjusted mean change from baseline in target area hair count in the vertex at week 12 and at week 24 (primary efficacy endpoint) in the intention to treat the population for both dosage forms are indicated below with a P value < 0.001 in comparison to placebo.

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Treatment-emergent adverse events (TEAEs) were assessed to check the safety profile for both dosage forms. These were 2.8% in topical dosage form and 4.8% in oral dosage form indicating that topical finasteride is relatively safer in comparison to oral finasteride. The drug concentrations within the plasma were 48.0 ± 87.2 pg/mL for topical finasteride and 5029 ± 4182 pg/mL for oral finasteride after the course of treatment i.e. 24 weeks (in the trial). This indicated that topical finasteride did not result in a significant concentration within the plasma in comparison to oral finasteride thus showing decreased sexual adverse effects. Thus, we can conclude that topical finasteride is well tolerated and significantly increases hair count. It has a comparable effect as oral finasteride but with significantly less systemic exposure and less of an impact on blood DHT levels.

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Market Offerings: An Overview of Topical Finasteride Products

Topical finasteride is currently available in different dosage forms like gels, topical sprays and creams. “Xyon” is the only Finasteride containing gel-based dosage form with a concentration of 2.5% that has a once-daily dose and a marketed price of $100. Most formulations incorporate finasteride with minoxidil to attain an enhanced effect. “Keeps”, another gel-based product, contains both finasteride (0.25%) and minoxidil (5%). It has a dose of once daily and a market price of $40-$60. “Hims” is a spray-based dosage form containing finasteride and minoxidil in concentrations of 0.1% and 6%. Its intended dose is twice daily with a marketed price of $45-$50.

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Topical Finasteride: Challenges in Effective Delivery

The molecular weight of finasteride is 372.54 g/mol. This means that the large molecular size of the drug may hamper its permeation across the stratum corneum. The permeation of a drug across the stratum corneum depends on several other physicochemical characteristics and not just size. For instance, finasteride has decreased solubility (BCS-class II drug) so marketed formulations dissolve it in organic solvents. When these solvents evaporate the drug remains either on the scalp region or the upper layers of the epidermis which may hamper its efficacy due to its limited targeting towards the hair follicles. Moreover, topical dosage forms like sprays consist of organic solvents for the dissolution of the drug. These may lead to application-based side effects like irritation and redness that may eventually decrease patient compliance.

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The Future of Topical Finasteride

Current developments in topical finasteride highly focus on the formulation of novel drug delivery systems. The reason for formulating such systems is to enhance the permeation of the high molecular weight drug across various layers of the stratum corneum. Recently researched carrier systems include the development of various nanoparticles which are eventually integrated into topical solutions and gels. The nanoparticles are designed as a vehicle to carry the drugs with size, permeability or solubility issues. The drugs are encapsulated within a matrix or a lipid vesicle and delivered to the targeted site. These systems not only enhance the permeation but also help to counter the problems associated with the application (redness, irritation) as they don’t employ the use of organic solvents (Khan et al., 2018). In our case, Finasteride has decreased tendency to permeate completely across stratum corneum (deeper layers) so recent studies are formulating nanoparticles and then incorporating them in gels or lotions etc. At present, pharmacokinetic studies are being conducted in vivo (in animal models). And the data (in vitro and In vivo currently available) has shown better release profiles and permeation profiles of the drug that can contribute towards higher efficacy for future clinical studies (Madheswaran et al., 2013).

The future prospective highly focuses on more clinical data evaluation for topical finasteride to understand its efficacy and long-term results. Moreover, advanced combination therapy is another area where finasteride can be combined with therapies like minoxidil to attain maximized efficacy. Furthermore, FDA approval must be sought for topical finasteride as it is currently being used as “off-label” for treating alopecia.

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References

Gupta, A., Venkataraman, M., Talkuder, M. & Bamimore, M. 2022. Finasteride for hair loss: a review. Journal of Dermatological Treatment, 33, 1938-1946.

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Khan, M. Z., Khan, S. A., Ubaid, M., Shah, A., Kousar, R. & Murtaza, G. 2018. Finasteride topical delivery systems for androgenetic alopecia. Current drug delivery, 15, 1100-1111.

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Libecco, J. F. & Bergeld, W. F. 2004. Finasteride in the treatment of alopecia. Expert Opinion on Pharmacotherapy, 5, 933-940.

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Piraccini, B. M., Blume‐Peytavi, U., Scarci, F., Jansat, J., Falqués, M., Otero, R., Tamarit, M., Galván, J., Tebbs, V. & Massana, E. 2022. Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial. Journal of the European Academy of Dermatology and Venereology, 36, 286-294.

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Irwig, M. S. 2012. Persistent sexual side effects of finasteride: could they be permanent? The journal of sexual medicine, 9, 2927-2932.

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Best Topical Finasteride. https://finvsfin.com/best-topical-finasteride

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Madheswaran, T., Baskaran, R., Thapa, R. K., Rhyu, J. Y., Choi, H. Y., Kim, J. O., Yong, C. S. & Yoo, B. K. 2013. Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery. Aaps Pharmscitech, 14, 45-52.