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Acne Treatment with Accutane Isotretinoin Part 1

Treatment with isotretinoin Part 1

Mechanisms of action, indications, treatment schedules, response, retreatment Oral isotretinoin or 13 cis-retinoic acid was introduced in 1982 as Accutane by Roche Pharmaceuticals It is the most effective and reliable treatment for acne. Isotretinoin treatment results in complete clearing and prolonged remissions in most patients. Many patients are cured of their acne after a single course of treatment. There are now two generic brands of isotretinoin.Isotretinoin is typically prescribed for 16 to 20 weeks. Most patients are clear at the end of this treatment period and many remain in remission. The reason for this remission is not entirely understood.

Isotretinoin mechanisms of action

Sebum suppression

Hyperkeratinization reduction

P. acnes reduction

Decreased inflammation

The drug effects all four factors in the pathogenesis of acne. Sebum production is profoundly reduced with a reduction in the range of 90%.

P. acnes numbers typically increase in the environment of excessive sebum and abnormally shed follicular cells that occurs in acne patients. P. acne numbers fall to very low levels as sebum production is reduced by isotretinoin. Acne inflammation is generated by proinflammatory substances produced by P. acnes. This P. acnes chemotaxis-induced inflammation stops as the numbers of P. acnes drop during treatment. Sebum and P. acnes levels increase after treatment is discontinued.

Indications

The indications for use of isotretinoin have expanded after years of treatment experience. Isotretinoin is first line therapy for severe cystic acne. Conventional topical and antibiotic therapy is a waist of time for patients with severe cystic acne. Delaying effective treatment increase the chance for scarring.

Indications for Isotretinoin

Nodulocystic acne

Unresponsive severe inflammatory acne

Papulopustular acne with scarring

Treatment resistant acne

Relapse after a course of antibiotics

Persistent acne for years

Acne with severe psychological distress

Marked seborrhea

Gram-negative folliculitis

Severe acne rosacea

Hidradenitis suppurative

Acne excoriated

Sebaceous hyperplasia

Isotretinoin was originally indicated for patients with severe nodular cystic acne. The next indication was for patients with severe inflammatory acne who did not respond to conventional therapy.

Scarring is preventable. Examine closely to determine the patients propensity to scar. Conventional treatment with topical preparations and oral antibiotics may be appropriate for patients who are scarring but treatment with isotretinoin should be started without delay if that short course of conventional treatment fails.

Isotretinoin is used for patients who have suffered with acne for years, or those whose acne flares when conventional therapy is tapered or stopped.

Patients with significant psychologic distress are not continued on long programs of ineffective conventional treatment. Promising that acne will be clear in 5 months provides immediate comfort.

Patients with very oily skin referred to as seborrhea are greatly relieved by isotretinoin. These patients are sometimes treated with very low doses for long periods of time.

Gram-negative folliculitis may follow long term treatment with antibiotics. It is treated with ampicillin, co-trimoxazole, trimethoprim and will also clear isotretinoin.

Isotretinoin is an option for treating severe rosacea and hidradenitis suppurativa. Rosacea may respond to doses as low as 10 mg/day. Acne excori?e in women may respond to isotretinoin.

Extensive sebaceous hyperplasia is disfiguring and responds rapidly to doses as low as 10 mg/day or 10 mg every other day and sometimes even lower doses.

Isotretinoin treatment schedules

Dosing at 1 mg/kg/day for 4 to 5 months results in the lowest rate of relapse. Isotretinoin should be taken with a fat containing food. The intensity of side effects increases with increasing dose. Start with 0.25 mg/kg/day or 0.5 mg/kg/day for the first 2 to 6 weeks. Increase the dose to 1.0 mg/kg/day if side effects are minimal. Initiate treatment with low doses for patients with severe cystic acne to decrease the chance ot stimulating an explosive flare.

The minimum total dose is 120 mg/kg. The rate of recurrence increases when lower doses are used. Most experts continue treatment until a total of 150 mg/kg has been reached. Lower daily dose courses require longer treatment times to reach a total dose of 150 mg/kg. An 80 kg man would take isotretinoin 40 mg twice each day for 20 weeks to reach a total dose of 150 mg per kg.

Some patients flare with inflammatory acne during the first month of therapy. Stop isotretinoin and start prednisone at 0.5-1.0 mg/kg/day.

An average of 1 to 3 months of prednisone is required to control flares.

Response

A cumulative dose of 150 mg/kg results in 60% of patients requiring no further treatment. Of those who experience a relapse, 21% respond to topical therapy, 16% require oral antibiotics, and 40% require no constant therapy. 23% of those who relapse require another course of isotretinoin.

Retreatment

Some patients relapse months or years after treatment. These patients may be treated with another course of isotretinoin with the same total dose of 150 mg/kg. Up to 5 courses have been prescribed for difficult patients by some experts. Women who flare may respond to spironolactone 100 to 200 mg/day and or oral contraceptives.