Frontline Forum Part 4: A Greater Understanding of the Acne Vulgaris Armamentarium

Continued from part 3

New Formulations of Isotretinoin

Newer formulations of isotretinoin have been developed that have higher bioavailability than traditional isotretinoin and do not require dosing with a high-fat meal.⁹ Lidose isotretinoin (Absorica) is presolubilized in a lipid matrix, which improves gastrointestinal absorption, and was found to have greater bioavailability than traditional isotretinoin when both drugs were taken in the fasted state.¹⁰ However, the bioavailability of lidose isotretinoin is greater when taken after a high-fat meal compared with the fasted state.¹⁰

A new formulation of micronized isotretinoin (Absorica LD) is dispersed in a lipid carrier system, resulting in greater surface area per unit mass and thereby higher rates of dissolution and bioavailability.¹¹ A study found that micronized isotretinoin 32 mg was bioequivalent to lidose isotretinoin 40 mg when patients had eaten, but its bioavailability in the fasted state was almost 2 times greater compared with lidose isotretinoin.11 Giving micronized isotretinoin with a high-fat meal did not affect rate of absorption and had a minimal effect on the extent of absorption.¹¹

The panelists noted the higher bioavailability of the newer isotretinoin formulations raises the question of the cumulative dose to target. Bunick noted that he often aims for a target cumulative dose of 200 mg/kg for traditional isotretinoin to minimize the relapse risk, but there is no clear information on how to translate this to micronized or lidose isotretinoin.

“One of the biggest barriers to using...newer formulations of isotretinoin is that when you have so much experience with conventional isotretinoin…you [rely on] this ‘art’ of dermatology and [your] feeling [about] what the patient needs to be cleared and technically cured; it [can be] very hard to translate into [measured] doses.”

Despite these challenges, the panelists said that the more bioavailable formulations of isotretinoin are advantageous for improving the likelihood of sustained remission with minimal concerns about timing the medication with a high-fat meal. The panelists also noted that the variability among generic versions of isotretinoin could result in different quantities of the drug being absorbed, and Baldwin noted that she prefers to prescribe brand-name versions to minimize the effects of this variable.

Monitoring Patient Outcomes With Isotretinoin

The 2016 American Academy of Dermatology guidelines recommend routine monitoring of serum lipid profiles and liver function tests (LFTs) for all patients on isotretinoin as well as pregnancy tests for female patients.¹ Bunick typically obtains baseline CBC, LFT, fasted lipid profile, and a pregnancy test, and rechecks these at 1 month and at every dose change. If changes in laboratory values occur with dose adjustments, he monitors that regularly during and 3 to 4 months after stopping isotretinoin treatment to ensure that levels have normalized. Baldwin noted that the isotretinoin-induced changes in laboratory values tend to be minor in her experience, but regular testing can help reduce the medicolegal costs and likelihood of consequences of not testing (eg, lawsuits).

Concluding Thoughts From Leading Physicians

The panelists concluded their discussion with advice for practitioners on optimization of AV treatment. Their advice included the 3 D’s: the importance of dosage, duration, and not delaying treatment. Bhatia recommended having patients try samples of topical therapy in the office so practitioners can instruct patients on how to use the product and they can provide feedback on how it feels on their skin. Strategizing the times of day that patients are best able to take their therapy is also important to cover during patient visits, he added. Bunick said that practitioners should ensure that patients promptly receive therapy for a sufficient duration to achieve a sustained response and, if they are taking isotretinoin, receive the newer formulations to maximize absorption.

“Don’t wait,” he said. “Get in there early when they show signs of inflammatory lesions, so that you can prevent the scarring. The whole point is to protect people long-term from scary consequences.”

To review the entire Frontline Forum series, click here.

Disclosure

This Frontline Forum is supported by Sun Pharmaceutical Industries Ltd.

References

1. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris (published correction appears in J Am Acad Dermatol. 2020 Jun;82(6):1576. J Am Acad Dermatol. 2016;74(5):945-973.e33. doi:10.1016/j.jaad.2015.12.037

9. Bellomo R, Brunner M, Tadjally E. New formulations of isotretinoin for acne treatment: expanded options and clinical implications. J Clin Aesthet Dermatol. 2021;14(12 suppl 1):S18-S23.

10. Absorica. Prescribing information. Ranbaxy Laboratories Inc. Updated May 2012. Accessed May 11, 2023.https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021951s000lbl.pdf

11. Madan S, Kumar S, Segal J. Comparative pharmacokinetic profiles of a novel low-dose micronized-isotretinoin 32 mg formulation and lidose-isotretinoin 40 mg in fed and fasted conditions: two open-label, randomized, crossover studies in healthy adult participants. Acta Derm Venereol. 2020;100(4):adv00049. doi:10.2340/00015555-3381