Clinical Overview: Isotretinoin (Absorica) for Severe Recalcitrant Nodular Acne

Isotretinoin exerts dose-dependent inhibition of sebaceous gland function, thereby reducing sebum secretion, which is associated with improvement in nodular acne.

Isotretinoin (Absorica) is an FDA-approved oral dosage form of isotretinoin indicated to treat severe recalcitrant nodular acne. The FDA initially approved this retinoid in 1982 and pharmaceutical firms have marketed it in various dosage forms over the past 40 years.1

Although very effective for nodular acne, pharmacists may be aware of oral isotretinoin’s disadvantages. Because isotretinoin is lipophilic, pharmacists have historically needed to counsel patients to take isotretinoin with a full, potentially higher fat meal. First approved in 2012, patients can take this specific lipid-encapsulated formulation without regard to meals.2-4

A double-blind, randomized, parallel group trial confirmed the efficacy of this isotretinoin formulation. Researchers randomized 925 patients 12 years of age and older with severe recalcitrant nodular acne to either lipid-encapsulated isotretinoin or another oral isotretinoin capsule.

All study participants received 0.5 mg/kg/day in 2 divided doses for 4 weeks, followed by 1 mg/kg/day in 2 divided doses for 16 weeks. The researchers screened participants for total nodular lesion count every 4 weeks during the trial.

At week 20, more than 70% of isotretinoin in both groups (70% in the lipid-encapsulated isotretinoin group vs 75% in the comparator group) experienced a 90% reduction in total nodular lesion count from their baseline measurements.1

Mechanism of Action

The exact mechanism regarding the treatment of nodular acne is not fully understood. Like other retinoids, isotretinoin generally affects epithelial cells. It exerts dose-dependent inhibition of sebaceous gland function, thereby reducing sebum secretion, which is associated with improvement in nodular acne.1 Isotretinoin may also have additional beneficial effects, inhibiting keratinization and inflammation.2,5

Dosage and Administration

This formulation of isotretinoin is only approved for non-pregnant patients 12 years of age or older. Patients must also have failed to respond to other therapies, including systemic antimicrobials.

Isotretinoin is initially dosed at 0.5 to 1 mg/kg/day in 2 divided doses for most patients. Some patients with severe nodular acne causing scarring or manifesting on the trunk may require treatment with 2 mg/kg/day in 2 divided doses (Table 1).

This particular form of isotretinoin can be given without regard to meals. Pharmacists should remember to dose based on actual body weight; however, the efficacy study cohort only included patients weighing up to 110 kg.

After a treatment duration of 15 to 20 weeks, prescribers can discontinue lipid-encapsulated isotretinoin if the total nodule count is reduced by at least 70%. A second course of therapy may be initiated but should not be started within 2 months of the previous course.

To avoid esophageal irritation, pharmacists should counsel patients to take their dose with a full glass of liquid. Patients forgetting a dose cannot take an extra dose and should be advised to skip the missed dose.

Adverse Events

The most common adverse events (AE) include dry skin, headache, increased creatinine kinase, upper respiratory infection, and reduced visual acuity. These AEs have been reported in 5% or more of patients treated with isotretinoin.

Warnings and Precautions

As previously suggested, isotretinoin therapy is associated with significant side effects and toxicities. Isotretinoin includes a boxed warning due to an extremely high risk of embryo-fetal toxicity in pregnant patients and is, therefore, contraindicated in pregnancy.

It is only available through the iPLEDGE risk evaluation and mitigation strategy (REMS) to prevent use in pregnancy. Patients, prescribers, and pharmacies must be certified and registered with the REMS program before treating any patient with isotretinoin.

Providers need to be aware of the risk of psychiatric disturbances, including suicidal ideation, associated with isotretinoin therapy. Pharmacists should counsel patients and caregivers to report changes in the patient’s mood or behavior to their prescribers.

Isotretinoin is contraindicated in patients with a previous allergic reaction to isotretinoin and vitamin A. Due to post-marketing reports of life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), providers need to monitor patients for skin reactions.

Significant increases in triglycerides (>800 mg/dL) can occur in patients taking isotretinoin, and fatal cases of hemorrhagic pancreatitis have been reported. Lipid levels should be drawn at baseline and then periodically during treatment. Providers need to counsel patients to report any potential symptoms of pancreatitis at any time while receiving isotretinoin.

Pharmacists should counsel patients and caregivers to stop isotretinoin and contact the patient’s prescriber if any of these discussed symptoms occur. Due to an increased risk of intracranial hemorrhage with isotretinoin, concurrent tetracycline use should be avoided.

Pharmacists should also be aware of corticosteroids, phenytoin, and isotretinoin interactions. These agents can all potentially cause detrimental effects on musculoskeletal health and prescribers need to discuss concurrent therapy with patients.

Patients need to also avoid progesterone preparation, or “minipills,” as contraception due to inadequate contraceptive potential when given with isotretinoin. Pharmacists need to caution patients against the use of St. John’s Wort because of reports of pregnancies when combined with hormonal contraceptives.

Pregnancy/Lactation

Serious fetal harm, including congenital malformations and spontaneous abortion, can occur after isotretinoin use in pregnancy. Any patient capable of becoming pregnant must follow all iPLEDGE requirements, including 2 confirmed negative CLIA-certified laboratory conducted pregnancy tests. Pregnancy tests must be repeated each month, at the end of isotretinoin treatment, and one month after isotretinoin therapy discontinuation.

Patients who can become pregnant need to use 2 simultaneous forms of contraception for 1 month preceding, during, and 1 month after receiving isotretinoin. If unprotected sex occurs during this time, patients should stop taking isotretinoin and contact their prescriber for further instructions.

If a patient becomes pregnant, isotretinoin must be immediately discontinued. Further follow-up should occur with an OBGYN practitioner. Any fetal exposure to isotretinoin should be reported to FDA MedWatch and the iPLEDGE registry.

Due to potential infant risk, patients should be advised that breastfeeding is not recommended during treatment with isotretinoin and for at least 8 days after the last dose of isotretinoin.1

About the Author

Edmond M Nunes, PharmD, RPh, BCSCP is the pharmacy clinical coordinator at Sturdy Memorial Hospital in Attleboro, MA.

References

1. Absorica/Absorica LD is prescribing information. November 2019. Accessed May 14, 2022. https://www.absoricald.com/pdf/absoricald-prescribing-information.pdf

2. Kircik LH. Why absorica LD? J Drugs Dermatology. 2021;20(5):s3-4. doi: 10.36849/JDD.s0721.

3. Jones M, Armstrong AW, Baldwin H, et al. Advances in oral isotretinoin therapy. J Drugs Dermatology. 2021;20(5):s5-s11. doi: 10.36849/JDD.s072A.

4. Zaenglein AI, Pathy AI, Sclosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-73.

5. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2021;379:361-72. doi: 10.1016/s0140-6736(11)60321-8.