DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 65–6
Photochemotherapy Methods
PUVA PHOTODYNAMIC THERAPY PHOTOPHERESIS
Target Broad cutaneous area Focal cutaneous sites Peripheral blood leukocytes
Photosensitizing agent Methoxsalen (8-methoxypsoralen) Protoporphyrin IX Methoxsalen
Trioxsalen (4,5′,8-trimethylpsoralen)
Bergapten (5-methoxypsoralen)
Method of drug Oral Topical cream or solution To isolated plasma within
administration Topical lotion of a prodrug photopheresis device
Bath water
(aminolevulinic acid or
methylaminolevulinate)
FDA-approved Psoriasis Actinic keratosis Cutaneous T-cell lymphoma
indications
Vitiligo
Activating wavelength UVA2 (320-340 nm) 417 nm and 630 nm UVA2 (320-340 nm)
Adverse effects (acute) Phototoxic reactions Phototoxic reactions Phototoxic reactions
Pruritus Temporary dyspigmentation GI disturbance
Hypertrichosis
Hypotension
GI disturbance
Congestive heart failure
CNS disturbance
Bronchoconstriction
Hepatic toxicity
Herpes simplex recurrence
Retinal damage
Adverse effects Photoaging Potential scarring Loss of venous access after
(chronic) Nonmelanoma skin cancer repeated venipuncture
Melanoma a
Cataracts a
Pregnancy category C b C b FDA unrated
a
Controversial. CNS, central nervous system; GI, gastrointestinal; UVA, ultraviolet A. b See Table 66–5 for pregnancy category.
diluted for use in bath water to minimize systemic absorption. An
extracorporeal solution (UVADEX) is available for cutaneous T-cell
lymphoma (see “Photopheresis”).
Approximately 90% of psoriatic patients have clearing or virtual
clearing of skin disease within 30 treatments with methoxsalen
(Morison, 2007). Remission typically lasts 3-6 months; thus, patients
often require maintenance therapy with intermittent PUVA or other
agents (Stern, 2007). Vitiligo typically requires between 150 and 300
treatments to produce satisfactory repigmentation. Localized vitiligo
can be treated with topical PUVA and more extensive disease with
systemic administration. PUVA also is employed off label in the
treatment of atopic dermatitis, alopecia areata, lichen planus, and
urticaria pigmentosa and as a preventive modality in some forms of
photosensitivity.
Toxicity and Monitoring. The major side effects of PUVA are listed
in Table 65–6. Phototoxicity is characterized by erythema, edema,
blistering, and pruritus. Ocular toxicity can be prevented by
wearing UVA-blocking glasses the day of treatment. The risk of
nonmelanoma skin cancer is dose dependent, with the greatest risk
in those receiving >250 treatments. A possible association of
melanoma and extensive exposure to PUVA has been reported;
however, several other studies have failed to confirm this association
(Morison, 2007). As skin cancer may not develop for decades
after exposure, annual skin exams should be continued for years
after completion of PUVA.
Photopheresis. Extracorporeal photopheresis (ECP) is a
process in which extracorporeal peripheral blood
mononuclear cells are exposed to UVA radiation in the
presence of methoxsalen. Although previously given
orally (Edelson et al., 1987), methoxsalen (UVADEX)
now is injected directly into the extracorporeal plasma
before radiation and reinfusion. The treated lymphocytes
are returned to the patient undergoing apoptosis
over 48-72 hours (McKenna et al., 2006).