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

mild penile irritation. Cross-allergenicity among these compounds is
assumed to exist, based on their structural similarities.
Oral Use. Use of the oral troche of clotrimazole is properly considered
as topical therapy. The only indication for this 10-mg troche is
oropharyngeal candidiasis. Antifungal activity is due entirely to the
local concentration of the drug; there is no systemic effect.
Clotrimazole
dose appears to be absorbed into the blood. Approximately 3% of
recipients have local erythema, burning, stinging, or itching.
Econazole nitrate (SPECTAZOLE, ECOSTATIN, others) is available as a
water-miscible cream (1%) to be applied twice a day.
Miconazole
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CHAPTER 57
Absorption of clotrimazole is <0.5% after application to the intact
skin; from the vagina, it is 3-10%. Fungicidal concentrations remain
in the vagina for as long as 3 days after application of the drug. The
small amount absorbed is metabolized in the liver and excreted in
bile. In adults, an oral dose of 200 mg/day will give rise initially to
plasma concentrations of 0.2-0.35 μg/mL, followed by a progressive
decline.
In a small fraction of recipients, clotrimazole on the skin may
cause stinging, erythema, edema, vesication, desquamation, pruritus,
and urticaria. When it is applied to the vagina, ~1.6% of recipients
complain of a mild burning sensation, and rarely of lower
abdominal cramps, a slight increase in urinary frequency, or skin
rash. Occasionally, the sexual partner may experience penile or urethral
irritation. By the oral route, clotrimazole can cause GI irritation.
In patients using troches, the incidence of this side effect is ~5%.
Therapeutic Uses. Clotrimazole is available as a 1% cream, lotion,
powder, aerosol solution, and solution (LOTRIMIN AF, MYCELEX,
others), 1% or 2% vaginal cream, or vaginal tablets of 100, 200, or
500 mg (GYNE-LOTRIMIN, others), and 10-mg troches (MYCELEX, others).
On the skin, applications are made twice a day. For the vagina,
the standard regimens are one 100-mg tablet once a day at bedtime
for 7 days, one 200-mg tablet daily for 3 days, one 500-mg tablet
inserted only once, or 5 g of cream once a day for 3 days (2% cream)
or 7 days (1% cream). For oropharyngeal candidiasis, troches are to
be dissolved slowly in the mouth five times a day for 14 days.
Topical clotrimazole cures dermatophyte infections in
60-100% of cases. The cure rates in cutaneous candidiasis are
80-100%. In vulvovaginal candidiasis, the cure rate is usually >80%
when the 7-day regimen is used. A 3-day regimen of 200 mg once a
day appears to be similarly effective, as does single-dose treatment
(500 mg). Recurrences are common after all regimens. The cure rate
with oral troches for oral and pharyngeal candidiasis may be as high
as 100% in the immunocompetent host.
Miconazole readily penetrates the stratum corneum of the skin and
persists there for >4 days after application. Less than 1% is absorbed
into the blood. Absorption is no more than 1.3% from the vagina.
Adverse effects from topical application to the vagina include
burning, itching, or irritation in ~7% of recipients, and infrequently,
pelvic cramps (0.2%), headache, hives, or skin rash. Irritation, burning,
and maceration are rare after cutaneous application. Miconazole
is considered safe for use during pregnancy, although some authors
avoid its vaginal use during the first trimester.
Therapeutic Uses. Miconazole nitrate is available as a 2% cream,
ointment, lotion, powder, gel, aerosol powder, and aerosol solution
(MICATIN, ZEASORB-AF, others). To avoid maceration, only the lotion
should be applied to intertriginous areas. Miconazole is available
as a 2% and 4% vaginal cream, and as 100-mg, 200-mg, or 1200-mg
vaginal suppositories (MONISTAT 7, MONISTAT 3, MONISTAT 1, others),
to be applied high in the vagina at bedtime for 7, 3, or 1 day(s),
respectively.
In the treatment of tinea pedis, tinea cruris, and tinea versicolor,
the cure rate may be >90%. In the treatment of vulvovaginal
candidiasis, the mycologic cure rate at the end of 1 month is ~80-95%.
Pruritus sometimes is relieved after a single application. Some vaginal
infections caused by Candida glabrata also respond.
Terconazole and Butoconazole
Terconazole (TERAZOL, others) is a ketal triazole. The mechanism of
action of terconazole is similar to that of the imidazoles. The 80-mg
vaginal suppository is inserted at bedtime for 3 days; the 0.4% vaginal
cream is used for 7 days and the 0.8% cream for 3 days. Clinical
efficacy and patient acceptance of both preparations are at least as
good as for clotrimazole in patients with vaginal candidiasis.
Butoconazole is an imidazole that is pharmacologically quite
comparable to clotrimazole. Butoconazole nitrate (FEMSTAT 3, others)
is available as a 2% vaginal cream; it is used at bedtime in nonpregnant
females. Because of the slower response during pregnancy, a
6-day course is recommended (during the second and third trimester).
ANTIFUNGAL AGENTS
Econazole
Econazole is the deschloro derivative of miconazole. Econazole
readily penetrates the stratum corneum and is found in effective
concentrations down to the mid-dermis. However, <1% of an applied
Tioconazole
Tioconazole (VAGISTAT 1, others) is an imidazole marketed for treatment
of Candida vulvovaginitis. A single 4.6-g dose of ointment
(300 mg) is given at bedtime.