A Textbook of Clinical Pharmacology and Therapeutics

ISOTRETINOIN

Uses

Isotretinoinis the D-isomer of tretinoin, another vitamin A
analogue. It is given orally for severe acne or rosacea and
should only be prescribed under hospital supervision. The
usual course is four months, with 80% improvement. Clinical
benefit continues after discontinuation of therapy.

Mechanism of action

The primary action of retinoids is inhibition of sebum produc-
tion, reducing the size of the sebaceous glands by 90% in the
first month. These drugs also inhibit keratinization of the hair
follicle, resulting in reduced comedones.

Adverse effects

These include the following:

• teratogenic effects;


• mucocutaneous effects – cheilitis, dry mouth, epistaxis,
  dermatitis, desquamation, hair and nail loss;


• central nervous system (CNS) effects – ocular
  (papilloedema, night blindness), raised intracranial
  pressure;


• musculoskeletal effects – arthralgia, muscle stiffness,
  skeletal hyperostosis, premature fusion of epiphyses;


• hepatotoxic effects;


• hypertriglyceridaemia.

Contraindications

Systemic use of any vitamin A analogue is contraindicated in
pregnant or breast-feeding women.

Pharmacokinetics

Isotretinoinis well absorbed (90%). Tissue binding is high

and it is eliminated over a period of at least one month after

treatment has been discontinued. This explains the ongoing

clinical benefit after stopping drug therapy and also the per-

sistent risk of teratogenicity after a course of treatment.

Isotretinoinis almost totally cleared from the body by hepatic

metabolism.

Drug interactions

There is an increased incidence of raised intracranial pressure

ifisotretinoinis prescribed with tetracyclines.

ALOPECIA AND HIRSUTISM

In androgenic baldness, it is possible to promote hair growth

by topical application of minoxidil sulphate (the active

metabolite of minoxidil). This is believed to have a mitogenic

effect on the hair follicles. Adverse effects include local itching

and dermatitis. Approximately 30% of subjects respond within

4–12 months, but hair loss recurs once therapy is discontinued.

In women, cyproterone acetatecombined with ethinylestra-

diolprevents the progression of androgenic alopecia.

The anti-androgen activity (both central and peripheral) of

cyproterone acetatemakes it the systemic drug of choice for

female hirsutism, if topical depilation has failed or the hirsutism

is too general. It is given with ethinylestradiolto prevent preg-

nancy (feminization of the fetus). Clinical improvement may

take 6–12 months.

Eflornithine, an irreversible inhibitor of ornithine decar-

boxylase, is a topical cream licensed for female facial hirsutism.

412 DRUGS AND THE SKIN

Topical keratolytic agents (benzoyl peroxide or tretinoin)

or

Topical antibiotics (e.g. tetracycline, clindamycin)

or

Topical azelaic acid

No Yes

Continue until acne cleared

No Yes

SPECIALISTS
ONLY

Consider: Continue until acne cleared

(may take several months)

Effective?

Effective?

Oral antibiotics (e.g. oxytetracycline,

erythromycin)

cyproterone ethinylestradiol

(women only)

isotretinoin

• 
  


• Figure 51.1:Pathway for
  treatment of acne.