Состав
В 100 г крема изоконазола нитрата 1 г. Полисорбат 60, сорбитана стеарат, цетиловый спирт, парафин г, вазелин, вода, как вспомогательные вещества.
В 1 суппозитории изоконазола нитрата 600 мг и твердый жир, как вспомогательный компонент.
Форма выпуска
Крем 1% в тубах 20 и 50 г.
Свечи 600 мг №1.
Фармакологическое действие
Противогрибковое, антибактериальное.
Фармакодинамика и фармакокинетика
Фармакодинамика
Активное вещество изоконазола нитрат является синтетическим производным имидазола. В обычной концентрации оказывает фунгистатический эффект, при ее увеличении — фунгицидный. Ингибирует синтез эргостерола (основной компонент клеточной мембраны) и изменяет состав мембраны. Спектр действия включает дерматофиты, дрожжи и дрожжеподобные грибы, плесневые грибы, а также стафилококки, стрептококки, микрококки и возбудителя эритразмы. На простейших и бактерий не действует. При длительном постепенно развивается устойчивость. Все препараты изоконазола предназначены для местного применения.
Фармакокинетика
При местном применении крема создаются высокие концентрации в слоях кожи. Системная абсорбция минимальна.
При введении суппозитория образуется депо активного вещества во влагалище. Суппозиторий образует вязкую массу, обволакивающую стенки влагалища. Часть вещества растворяется и попадает в эпителий влагалища. Концентрация противогрибкового средства поддерживается во влагалище нескольких дней. При одноразовом применении менее 5% дозы абсорбируется. Абсорбированный изоконазол метаболизируется полностью.
Показания к применению
Для крема:
- микозы стоп и кожи;
- трихофития, микроспория, руброфития;
- кандидамикозы;
- эпидермофития;
- эритразма;
- разноцветный лишай.
Для свечей:
- грибковые инфекции влагалища;
- смешанные инфекции (грибковые и бактериальные).
Противопоказания
- повышенная чувствительность;
- возраст до 18 лет (для свечей);
- возраст до 1 месяца (для крема).
С осторожностью назначается при беременности и в период лактации.
Побочные действия
Местные аллергические реакции, болезненность в месте нанесения, жжение, покраснение, зуд.
В редких случаях в течение 12 часов после введения свечи отмечается жжение и зуд во влагалище.
Изоконазол, инструкция по применению (Способ и дозировка)
Мазь, содержащая Изоконазол (точнее крем), выпускается под торговым названием Травоген. Его наносят на кожу 1 раз в сутки тонким слоем и втирают. Длительность лечения 3 недели, при локализации процесса в складках — 4 недели. Чтобы избежать рецидива нужно еще в течение 14 дней продолжать лечение. На пораженные пальцы рук и ног можно накладывать повязку с изоконазолом. Лечение детей до 2 лет нужно проводить под контролем врача. При раздражении кожи и симптомах гиперчувствительности лечение отменяют. Избегать попадания в глаза. При отсутствии эффекта нужно обратиться к врачу.
Свечи, содержащие Изоконазол имеют торговое название Гино-Травоген овулум. Их вводят во влагалище один раз, лучше на ночь. Лечение может составлять 1-3 дня. Его не проводят по время менструации. В течение недели после применения избегать спринцеваний, а также нельзя пользоваться тампонами.
Передозировка
Случаи передозировки не известны.
Взаимодействие
Не выявлено взаимодействия с другими лекарственными средствами.
Условия продажи
Без рецепта.
Условия хранения
Температура 15-25°С.
Срок годности
Суппозитории и крем 5 лет.
Аналоги
Совпадения по коду АТХ 4-го уровня:
Травоген, Гино-Травоген овулум, Травокорт (с глюкокортикоидом).
Отзывы об Изоконазоле
Широкое применение противомикотических препаратов влечет распространение устойчивых форм возбудителей. Поэтому разрабатываются новых противогрибковые препараты с более высокой, эффективностью, лучшей переносимостью и меньшей токсичностью. Производные имидазола (их называют еще азолы), к которым относится и данное лекарственное средство, наиболее многочисленная группа. Обладают широким спектром действия, но все же, из азолов самый широкий спектр имеют вориконазол и итраконазол.
Антибактериальный эффект крема в сочетании с антимикотической активностью позволяют использовать его при лечении дерматозов, вызванных смешанной инфекцией.
- «… С помощью этого крема вылечил дерматит. Высеяли грибок и стафилококк. Лечил целый месяц, потом сдал анализ».
- «… У меня запущенный дерматит и сильное воспаление. Помог только Травокорт с гормоном».
- «… У дочки в 3,5 года был «стригущий» лишай. Вылечились мазью Травоген, по мазали 2 раза и почти 2 месяца».
- «… Помог от грибка на ноге. Зуд и покраснение прошли через 2 дня, но для убедительного лечения мазал в целом 3 недели. Крем не дешевый».
- «… В паховых складках краснота и зуд. Соскоб показал грибы. Выписали этот крем, прошла месячный, но улучшений нет. Краснота увеличивается и сильный зуд продолжается».
- «… Был потрясающий эффект при применении Травокорта с Травогеном при грибке паховой области. За полтора месяца прошло всё, а мучился 2 года».
- «… Применяла этот крем при кандидозном кольпите. Дважды в день целую неделю смазывала кремом наружные половые органы. Хорошо помог».
Суппозитории применяются местно для лечения кандидозных вульвовагинитов. При легком течении заболевания, когда нет необходимости в приеме системных антимикотиков, достаточно только местного лечения. Согласно клиническим исследованиям по применению этих свечей выздоровление наступало у 88% пациенток, что подтверждалось лабораторными данными — отсутствие грибка. Свечи, так же, как и крем могут быть использованы при влагалищных инфекциях грибкового и смешанного генеза. Отзывы о суппозиториях разноплановые — кому-то быстро помогли, кто-то отмечает их неэффективность. Многие отмечают его хорошую переносимость.
- «... Замучила молочница после родов. Долго подбирала препараты и перепробовала многие в течение 3-х лет. Все со временными улучшениями и снова зуд. Эти свечи применяла 2 дня подряд. Уже полгода не беспокоят зуд и выделения».
- «… Свечка помогла с первого раза. Можно и беременным».
- «… Мне не помогли. Через неделю все вернулось назад. Видимо все зависит от организма и иммунитета».
Цена Изоконазола, где купить
Крем Травоген 1% 20 г можно приобрести за 523-619 руб., стоимость вагинальных свечей Гино-Травоген овулум составляет 1595-1750 руб.
Rec.INN
зарегистрированное ВОЗ
Входит в состав препаратов:
список
Фармакологическое действие
Противогрибковое средство для наружного применения. Изоконазол — синтетическое производное имидазола. Действует фунгистатически на дерматофиты, дрожжеподобные и плесневые грибы. Активен в отношении Corynebacterium minutissimum и некоторых грамположительных бактерий.
Фармакокинетика
При нанесении на кожу системная абсорбция незначительна.
После наружного применения изоконазол быстро проникает в кожу, Cmax в роговом слое и в нижележащих слоях эпидермиса достигается уже через 1 ч после нанесения. Концентрация изоконазола в эпидермисе выше, чем в дерме и подкожной клетчатке.
Показания активного вещества
ИЗОКОНАЗОЛ
Поверхностные грибковые поражения кожи, в т.ч. с локализацией в складках кожи, межпальцевых промежутках, паховой области, области наружных половых органов; эритразма.
Режим дозирования
Применяют наружно. Наносят на пораженные участки кожи 1 раз/сут. Обычная продолжительность наружной терапии составляет 2-3 недели, в случае плохо поддающихся терапии инфекций (особенно в области межпальцевых промежутков) — 4 недели.
У детей применяют под наблюдением врача. Коррекция режима дозирования не требуется.
Побочное действие
Со стороны кожи и подкожных тканей: нечасто — мокнущая экзема, дисгидроз, контактный дерматит; частота неизвестна -аллергические кожные реакции.
Местные реакции: часто — раздражение и жжение в месте нанесения; нечасто — сухость и зуд в месте нанесения; редко — припухлость и трещины в месте нанесения; частота неизвестна — эритема и везикулы в месте нанесения.
Противопоказания к применению
Повышенная чувствительность к изоконазолу.
Применение при беременности и кормлении грудью
При беременности следует применять только после консультации с врачом, в тех случаях, когда предполагаемая польза для матери превышает потенциальный риск для плода.
В период лечения необходимо решить вопрос о прекращении грудного вскармливания.
Применение у детей
У детей применяют с осторожностью, под наблюдением врача, строго по показаниям, в рекомендуемых соответственно возрасту дозах и лекарственных формах.
Особые указания
Следует избегать попадания изоконазола в глаза.
Изоконазол
Isoconazole
Фармакологическое действие
Изоконазол оказывает антибактериальное, противогрибковое и фунгистатическое действие.
Фармакодинамика
Изоконазол — противогрибковый препарат, синтетическое производное имидазола. Действует фунгистатически на дерматофиты, дрожжеподобные и плесневые грибы, при увеличении концентрации действует фунгицидно. Подавляет синтез эргостерола и изменяет состав мембраны микробной клетки. Активен в отношении дерматофитов (Trychophyton spp., Microsporum spp., Epidermophyton spp.); плесневых, дрожжевых и дрожжеподобных грибов (Candida spp., Pityrosporum orbiculare), а также Corynebacterium minutissimum — возбудителя эритразмы и грамположительных бактерий Staphylococcus spp., Streptococcus spp.
Фармакокинетика
Препарат для местного применения, абсорбция незначительная, не оказывает системного действия.
Показания
Дерматомикозы:
- трихофития, эпидермофития, микроспория, кандидоз; поражения, вызванные плесневыми грибами;
- инфекционно-воспалительные заболевания влагалища.
Противопоказания
Повышенная чувствительность.
Беременность и грудное вскармливание
Применение при беременности
Категория действия на плод по FDA — N.
Применение изоконазола в период беременности возможно по назначению врача и, если потенциальная польза для матери превышает возможный риск для плода.
Применение в период грудного вскармливания
Не установлено, проникает ли изоконазол в грудное молоко, поэтому препарат не следует наносить на грудные железы перед кормлением. При необходимости применения препарата необходимо решить с врачом вопрос о прекращении грудного вскармливания.
Применение в детском возрасте
Лечение детей с 1 месяца до 2 лет проводится под наблюдением врача.
Способ применения и дозы
Наружно.
Наносят на поражённые участки кожи 1 раз в сутки. Курс лечения составляет не менее 4 недель. Во избежание рецидива необходимо продолжить лечение ещё 2 недели после клинического выздоровления. Интравагинально применяют 1 раз в сутки вечером перед сном.
Побочные действия
Редко может развиться раздражение (ощущение жжения и зуда, эритема), крайне редко — кожные аллергические реакции.
Меры предосторожности
Следует избегать попадания изоконазола в глаза. При случайном попадании препарата в глаза следует тщательно промыть их тёплой водой.
Интравагинально не применяют в период менструации.
Классификация
-
АТХ
D01AC05, G01AF07
-
Фармакологические группы
-
Коды МКБ 10
-
Категория при беременности по FDA
N
(не классифицировано FDA)
Информация о действующем веществе Изоконазол предназначена для медицинских и фармацевтических специалистов, исключительно в справочных целях. Инструкция не предназначена для замены профессиональной медицинской консультации, диагностики или лечения. Содержащаяся здесь информация может меняться с течением времени. Наиболее точные сведения о применении препаратов, содержащих активное вещество Изоконазол, содержатся в инструкции производителя, прилагаемой к упаковке.
Isoconazole
Christine D. Waugh, in xPharm: The Comprehensive Pharmacology Reference, 2007
Isoconazole; adestan; 1 [2,4 dichlorobeta (2,6 dichlorobenzyloxy)phenethyl]imidazole; 1 [2 (2,4 dichlorophenyl) 2[(2,6 dichlorophenyl)methoxy]ethyl] 1h imidazole; fazol; fazol g; gynotravogen; gynotravogen; icaden; isoconazole nitrate; r 15,454; r 15454; travogen; travogyn; 1 [2 (2,4 dichlorophenyl) 2 [(2,6 dichlorophenyl)methoxy]ethyl] 1h imidazole; 1 [2,4 dichloro beta (2,6 dichlorobenzyloxy)phenethyl]imidazole; gyno travogen
Read full chapter
URL:
https://www.sciencedirect.com/science/article/pii/B9780080552323619567
Antifungal Agents
A. Espinel-Ingroff, in Encyclopedia of Microbiology (Third Edition), 2009
Econazole, isoconazole, oxiconazole, and tioconazole
Other frequently used topical imidazoles include econazole (1% cream), isoconazole (1% cream), oxiconazole (1% cream and lotion), and tioconazole (6.5% vaginal ointment) (Table 1). As with clotrimazole, a single application of tioconazole is effective in the management of vulvovaginal candidiasis and as a nail lacquer for fungal onychomycosis (nail infections). Mild to moderate vulvovaginal burning has been associated with intravaginal therapy. Oxiconazole and econazole are less effective than terbinafine and itraconazole in the treatment of onychomycosis and other infections caused by the dermatophytes. Although topical agents do not cure onychomycosis as oral drugs do, they may slow down the spread of this infection. However, the recommended drugs for the treatment of onychomycosis are terbinafine (by dermatophytes) and itraconazole.
Read full chapter
URL:
https://www.sciencedirect.com/science/article/pii/B978012373944500331X
Antibacterial drugs
Mark Farrington, in Clinical Pharmacology (Eleventh Edition), 2012
Azoles
This group includes:
- •
-
Metronidazole and tinidazole (antibacterial and antiprotozoal) which are described here.
- •
-
Fluconazole, itraconazole, clotrimazole, econazole, ketoconazole, isoconazole and miconazole which are described under Antifungal drugs (p. 223).
- •
-
Albendazole, mebendazole and thiabendazole which are described under Anthelminthic drugs (p. 236).
Metronidazole
In obligate anaerobic microorganisms (but not in aerobes) metronidazole is converted into an active form by reduction of its nitro group: this binds to DNA and prevents nucleic acid formation; it is bacteriostatic.
Pharmacokinetics
Metronidazole is well absorbed after oral or rectal administration and distributed widely. It is eliminated in the urine, partly unchanged and partly as metabolites. The t½ is 8 h.
Uses
Metronidazole’s clinical indications are:
- •
-
Treatment of sepsis to which anaerobic organisms, e.g. Bacteroides spp. and anaerobic cocci, are contributing, including post-surgical infection, intra-abdominal infection and septicaemia, osteomyelitis and abscesses of brain or lung.
- •
-
Antibiotic-associated pseudomembraneous colitis (caused by Clostridium difficile).
- •
-
Trichomoniasis of the urogenital tract in both sexes.
- •
-
Amoebiasis (Entamoeba histolytica), including both intestinal and extra-intestinal infection.
- •
-
Giardiasis (Giardia lamblia).
- •
-
Acute ulcerative gingivitis and dental infections (Fusobacterium spp. and other oral anaerobic flora).
- •
-
Anaerobic vaginosis (Gardnerella vaginalis and vaginal anaerobes).
Dose
Established anaerobic infection is treated with metronidazole by mouth 400 mg 8-hourly; by rectum 1 g 8-hourly for 3 days followed by 1 g 12-hourly; or by i.v. infusion 500 mg 8-hourly. A topical gel preparation is useful for reducing the odour associated with anaerobic infection of fungating tumours.
Adverse effects
include nausea, vomiting, diarrhoea, furred tongue and an unpleasant metallic taste in the mouth; also headache, dizziness and ataxia. Rashes, urticaria and angioedema occur. Peripheral neuropathy occurs if treatment is prolonged and epileptiform seizures if the dose is high. Large doses of metronidazole are carcinogenic in rodents and the drug is mutagenic in bacteria; long-term studies have failed to discover oncogenic effects in humans.
A disulfiram-like effect (see p. 147) occurs with alcohol because metronidazole inhibits alcohol and aldehyde dehydrogenase; patients should be warned appropriately.
Tinidazole
is similar to metronidazole in use and adverse effects, but has a longer t½ (13 h). It is excreted mainly unchanged in the urine. The longer duration of action of tinidazole may be an advantage, e.g. in giardiasis, trichomoniasis and acute ulcerative gingivitis, in which tinidazole 2 g by mouth in a single dose is as effective as a course of metronidazole.
Read full chapter
URL:
https://www.sciencedirect.com/science/article/pii/B9780702040849000525
Viral, fungal, protozoal and helminthic infections
Sani Aliyu, in Clinical Pharmacology (Eleventh Edition), 2012
Azoles
The antibacterial, antiprotozoal and anthelminthic members of this group are described in the appropriate sections. Antifungal azoles comprise the following:
- •
-
Imidazoles (ketoconazole, miconazole, fenticonazole, clotrimazole, isoconazole, tioconazole) interfere with fungal oxidative enzymes to cause lethal accumulation of hydrogen peroxide; they also reduce the formation of ergosterol, an important constituent of the fungal cell wall which thus becomes permeable to intracellular constituents. Lack of selectivity in these actions results in important adverse effects.
- •
-
Triazoles (fluconazole, itraconazole, voriconazole, posaconazole) damage the fungal cell membrane by inhibiting lanosterol 14-α-demethylase, an enzyme crucial to ergosterol synthesis, resulting in accumulation of toxic sterol precursors. Triazoles have greater selectivity against fungi, better penetration of the CNS, resistance to degradation and cause less endocrine disturbance than do the imidazoles.
Ketoconazole
Ketoconazole is well absorbed from the gut (poorly where there is gastric hypoacidity; see below); it is widely distributed in tissues but concentrations in CSF and urine are low; its action is terminated by metabolism by cytochrome P450 3A (t½ 8 h). For systemic mycoses, ketoconazole (see Table 15.3) has been superseded by fluconazole and itraconazole on grounds of improved pharmacokinetics, tolerability and efficacy. Impairment of steroid synthesis by ketoconazole has been put to other uses, e.g. inhibition of testosterone synthesis lessens bone pain in patients with advanced androgen-dependent prostatic cancer.
Adverse reactions
include nausea, giddiness, headache, pruritus and photophobia. Impairment of testosterone synthesis may cause gynaecomastia and decreased libido in men. Of particular concern is impairment of liver function, ranging from a transient increase in levels of hepatic transaminases and alkaline phosphatase to severe injury and death.
Interactions
Drugs that lower gastric acidity, e.g. antacids, histamine H2-receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes, inhibiting their action and thereby increasing effects of oral anticoagulants, phenytoin and ciclosporin, and increasing the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole.
Other imidazoles
Miconazole is an alternative. Clotrimazole is widely used as an effective topical agent for dermatophyte, yeast and other fungal infections (intertrigo, athlete’s foot, ringworm, pityriasis versicolor, fungal nappy rash). Econazole and sulconazole are similar. Tioconazole is used for fungal nail infections, and isoconazole and fenticonazole for vaginal candidiasis.
Fluconazole
Fluconazole is absorbed from the gastrointestinal tract and is excreted largely unchanged by the kidney (t½ 30 h). It is effective by mouth for oropharyngeal and oesophageal candidiasis, and i.v. for systemic candidiasis and cryptococcosis (including cryptococcal meningitis; it penetrates the CSF well). It is used prophylactically in a variety of conditions predisposing to systemic candida infections, including at times of profound neutropenia after bone marrow transplantation, and in patients in intensive care units who have intravenous lines in situ, are receiving antibiotic therapy and have undergone bowel surgery. It may cause gastrointestinal discomfort, headaches, reversible alopecia, increased levels of liver enzymes and allergic rash, but is generally well tolerated. Animal studies demonstrate embryotoxicity and there have been reports of multiple congenital abnormalities in women treated with long-term high-dose fluconazole, therefore fluconazole should be avoided in pregnant women. High doses increase the effects of phenytoin, ciclosporin, zidovudine and warfarin.
Itraconazole
Itraconazole is available for oral (suspension and capsule) and i.v. administration (t½ 25 h, increasing to 40 h with continuous treatment). The intravenous preparation is not available in many countries. Absorption from the gut is about 55%, but variable. It is improved by ingestion with food, but decreased by fatty meals and therapies that reduce gastric acidity. Plasma concentrations should be monitored during prolonged use for critical indications. The oral suspension formulation has significantly improved bio-availability compared to the capsule formulation and is much less affected by gastric hypoacidity. Itraconazole is heavily protein bound and virtually none is found within the CSF. It is almost completely oxidised in the liver (by CYP 3A) and excreted in the bile; little unchanged drug enters the urine.
Itraconazole is used for a variety of superficial mycoses, as a prophylactic agent for aspergillosis and candidiasis in the immunocompromised, and i.v. for treatment of histoplasmosis. It is licensed in the UK as a second-line agent for Candida, Aspergillus and Cryptococcus infections, and it may be convenient as ‘follow-on’ therapy after systemic aspergillosis has been brought under control by an amphotericin preparation. It appears to be an effective adjunct treatment for allergic bronchopulmonary aspergillosis.
Adverse effects
are uncommon, but include transient hepatitis and hypokalaemia. Prolonged use may lead to cardiac failure, especially in those with pre-existing cardiac disease. Co-administration of a calcium channel blocker adds to the risk. Cyclodextrin (used as a vehicle for the i.v. formulation) accumulates and causes sodium overload in renally impaired patients, but the oral formulation avoids this problem.
Interactions
Enzyme induction of CYP 3A, e.g. by rifampicin, reduces the plasma concentration of itraconazole. Additionally, its affinity for several P450 isoforms, notably CYP 3A4, causes it to inhibit the oxidation of a number of drugs, including phenytoin, warfarin, ciclosporin, tacrolimus, midazolam, triazolam, cisapride and terfenadine (see above), increasing their intensity and/or duration of effect.
Voriconazole
Voriconazole (t½ 7 h) is more active in vitro than itraconazole against Aspergillus because of more avid binding of the sterol synthetic enzymes of filamentous fungi; it also appears to have synergistic activity against Aspergillus in combination with amphotericin. It is as active as the other triazoles against yeasts and is more reliably and rapidly absorbed than itraconazole by mouth, but cross-resistance between these agents is usual. It is more effective than conventional amphotericin in invasive aspergillosis, and probably equivalent to lipid-associated formulations. Oral absorption is not significantly reduced by gastric hypoacidity. CSF and brain tissue concentrations are at least 50% of those in the plasma, and are sufficient for effective therapy of fungal infections of the eye and CNS.
Adverse effects
Administration i.v. gives rise rapidly to transient visual disturbance in 30% of patients (blurring, alerted visual perception such as reversal of light and dark, visual hallucinations and photophobia). These often resolve after the first week of therapy, and almost all of those affected are able to continue with the course of treatment.
Accumulation of the cyclodextrin vehicle (see above) may cause sodium retention in renally impaired patients with i.v. use. Patients with hepatic cirrhosis should receive a standard loading, but only half of the daily maintenance dose. Transiently raised liver enzyme levels are seen in up to 20% of patients, but serious liver impairment is rare. Rashes and photosensitivity appear to be more common than with the other triazoles.
Extensive metabolism of voriconazole by the cytochrome P450 system (predominantly CYP 2C19) may lead to unwanted interaction with patients receiving rifampicin, ciclosporin or tacrolimus.
Posaconazole
Posaconazole (t½ 20 h) is structurally related to itraconazole and has similar in vitro antifungal activity to voriconazole. It is fungistatic against Candida spp. but fungicidal against Aspergillus spp., and is also active against a range of other filamentous fungi. It provides effective prophylaxis against invasive fungal infection in leukaemia and bone marrow transplant patients. The oral bio-availabilty is high (90%), especially when taken with a fatty meal. More than 75% of the dose is excreted in the faeces.
Adverse effects
are uncommon, but include gastrointestinal disturbance, dizziness and fatigue, neutropenia (7% of patients) and transient disturbance of liver function. Dose adjustment is not required for renal or hepatic impairment.
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Antifungal agents
David W. Warnock, in Antibiotic and Chemotherapy (Ninth Edition), 2010
In addition to the systemic agents, numerous imidazoles are presently available for topical use. They include:
- •
-
Bifonazole. Used for the topical treatment of dermatophytoses and pityriasis versicolor.
- •
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Butoconazole. Used for the topical treatment of vaginal candidosis.
- •
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Clotrimazole. Used for the topical treatment of dermatophytoses, and oral, cutaneous and genital candidosis.
- •
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Econazole nitrate. Used for the topical treatment of dermatophytoses, and oral, cutaneous and genital candidosis. It has also been used to treat corneal infection.
- •
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Fenticonazole nitrate. Used for the topical treatment of vaginal candidosis.
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Isoconazole nitrate. Used for the topical treatment of dermatophytoses, and cutaneous and vaginal candidosis.
- •
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Miconazole nitrate. Used for the topical treatment of dermatophytoses, pityriasis versicolor, and oral, cutaneous and genital candidosis. (Formerly also available for intravenous use.)
- •
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Oxiconazole. Used for the topical treatment of dermatophytoses and cutaneous candidosis.
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Sertaconazole nitrate. Used for the topical treatment of dermatophytoses and vaginal candidosis.
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Sulconazole nitrate. Used for the topical treatment of dermatophytoses and cutaneous candidosis.
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Terconazole. Used for the topical treatment of dermatophytoses, and cutaneous and vaginal candidosis.
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Tioconazole. Used for the topical treatment of dermatophytoses (including nail infections), and cutaneous and vaginal candidosis.
Preparations and dosages
Bifonazole
Proprietary names: Amycor, Mycospor.
Preparation: Topical.
Dosage: For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Butoconazole
Proprietary name: Femstat.
Preparations: Pessaries, vaginal cream.
Dosage: Adults, pessaries, 100 mg per day for 3–6 consecutive days.
Widely available.
Clotrimazole
Proprietary names: Canesten, Gyne-Lotrimin, Lotrimin, Mycelex.
Preparations: Pessaries, vaginal cream, oral troche, topical.
Dosage: Adults, pessaries, 500 mg as a single dose, or 200 mg per day for 3 consecutive days, or 100 mg per day for 6 days. Oral troches, 10 mg five times daily for 2 weeks or longer. For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Econazole nitrate
Proprietary names: Ecostatin, Gyno-Pevaryl, Pevaryl, Spectazole.
Preparations: Pessaries, topical.
Dosage: Adults, pessaries, 150 mg per day for 3 consecutive days. For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Fenticonazole nitrate
Proprietary name: Lomexin.
Preparation: Pessaries.
Dosage: Adult, pessaries, 600 mg as a single dose or 200 mg per day for 3 consecutive days.
Widely available.
Isoconazole
Proprietary names: Fazol, Travogen, Travogyn.
Preparations: Pessaries, topical.
Dosage: Adult, pessaries, 600 mg as a single dose or 300 mg per day for 3 days. For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Miconazole nitrate
Proprietary names: Daktarin, Femeron, Gyno-Daktarin, Micatin, Micozole, Monistat.
Preparations: Pessaries, vaginal cream, oral gel, topical.
Dosage: Adults, pessaries, 200 mg per day for 7 consecutive days, or 100 mg per day for 14 days; oral gel, 125 mg every 6 h. Children 2–6 years, 125 mg every 12 h; infants <2 years, 62.5 mg every 12 h. For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Oxiconazole
Proprietary names: Oxistat, Oxizole.
Preparation: Topical.
Dosage: For fungal skin infections dosage and duration of treatment varies according to the condition being treated.
Widely available.
Sertaconazole nitrate
Proprietary name: Ertaczo
Preparation: Topical.
Dosage: For fungal skin infections dosage and duration of treatment varies according to condition.
Widely available.
Sulconazole nitrate
Proprietary name: Exelderm.
Preparation: Topical.
Dosage: For fungal skin infections dosage and duration of treatment varies according to the condition being treated.
Widely available.
Terconazole
Proprietary name: Terazol.
Preparations: Pessaries, vaginal cream.
Dosage: Adults, pessaries, 80 mg per day for 3 consecutive days.
Widely available.
Tioconazole
Proprietary names: Trosyd, Trosyl, Vagistat.
Preparations: Pessaries, nail solution, cream.
Dosage: Adults, pessaries, 300 mg as a single dose. For fungal skin and nail infections dosage and duration of treatment varies according to the condition being treated.
Widely available.
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In vitro and in vivo characterization of pharmaceutical topical nanocarriers containing anticancer drugs for skin cancer treatment
Vandana Gupta, Piyush Trivedi, in Lipid Nanocarriers for Drug Targeting, 2018
15.8.5.1 Tape stripping technique
The technique comprised of the standardized procedure of multiple applications and removal of adhesive tape on the skin surface, whereby successive layers of SC cells are sampled. As reported by Lademann et al. (2012) tape stripping is a standard method for the determination of the DPK of dermally applied isoconazole nitrate. These tape strips are appropriately applied and removed from the skin surface after application and permeation of topically applied components; accordingly, the layers of the SC and definite amount of topically applied components are removed. The amount of the components and the amount of corneocytes layers removed with the single tape strip is to be measured for calculation of the permeation profile. Dermal application of the components removed from the skin can be accordingly measured by various analytical techniques such as HPLC, Mass spectroscopy, and other spectroscopic measurements (Pople and Singh, 2013; Shah et al., 1998).
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Corticosteroids—glucocorticoids, topical, skin
In Meyler’s Side Effects of Drugs (Sixteenth Edition), 2016
General information
The local adverse effects of topical glucocorticoids [1,2] are listed in Table 1. They include transient local erythema, calcinosis cutis, cramps (due to injection of crystals into a vessel), amaurosis (a dubious report), depigmentation, skin atrophy, and skin necrosis [3].
Table 1. Adverse reactions to topical glucocorticoids
| Effects on the pilosebaceous unit | Effects on the immune system |
| Perioral dermatitis [14] | Aggravation of pre-existing folliculitis |
| Steroid rosacea or rosacea-like dermatitis | Development of extensive, but unrecognized dermatophytic infections (“tinea incognito”) |
| Steroid acne | Perpetuation of masked infections with Candida albicans |
| Exacerbation of pre-existing rosacea | Conversion of scabies into the Norwegian type |
| Hypertrichosis of the face | Widespread lesions of molluscum contagiosum |
| Atrophic changes | “Galloping” impetigo |
| Cigarette-paper wrinkling of the skin | (Possibly) exacerbation or dissemination of viral skin infections |
| Telangiectasiae [15] | Generalized pustular psoriasis |
| Petechiae, ecchymoses | Generalized urticaria |
| Striae rubrae distensae, mainly in the inguinal and axillary regions (occlusion effect) | Spreading of malignant skin lesions |
| Skin lesions | Suppression of pruritus |
| Acne | Allergic contact dermatitis [17–19] |
| Hirsutism | Systemic adverse effects of topical administration |
| Ecchymoses | Cushing’s syndrome |
| Milia | Suppression of the hypothalamic–pituitary–adrenal axis |
| Granuloma gluteale infantum | Growth retardation [20] |
| Pseudocicatrices stellaires spontanées | Hyperglycemia |
| Eczema craquelatum after withdrawal | Benign intracranial hypertension after withdrawal |
| Elastoidosis cutanée nodulaire à cystes et à comedones Favre-Raacouchot | Subcapsular cataract |
| Erythrosis interfollicularis colli | Pancreatitis |
| Cutis punctata linearis colli or “stippled skin” | Bony avascular necrosis [15] |
| Hypopigmentation | Psychiatric symptoms |
| Hyperpigmentation | Fluid retention |
| Striae | Hypertension [21] |
| Susceptibility of the skin to minor trauma | Miscellaneous |
| Fragile skin in surgery | Tachyphylaxis to the vasoconstrictor effect of topical glucocorticoids |
| Delayed wound healing | |
| Worsening of existing ulceration | |
| Photosensitivity of atrophic skin | |
| Ocular effects | |
| Ocular hypertension | |
| Open-angle glaucoma [16] | |
| Uveitis | |
| Posterior subcapsular cataracts [15] |
The systemic adverse effects of topical glucocorticoids [4–7], which are those to be expected from systemic use, are also listed in Table 1. The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic–pituitary–adrenal axis suppression, leading to clinically significant adrenal insufficiency or Cushing’s syndrome, is infrequent. In most cases in which systemic adverse effects occur, misuse of a product can be blamed. For example, a 4-month old boy developed iatrogenic Cushing’s syndrome, which occurred when his mother used excessive amounts of clobetasol 17-propionate and hydrocortisone 17-butyrate cream for 2 months to treat a diaper rash [8]. Two patients developed adrenal suppression after the unregulated use of betamethasone dipropionate 0.05% ointment (about 80 g/week) or clobetasol 0.05% ointment (up to 100 g/week), obtained without prescription to treat psoriasis [9].
Sensory systems
Two patients developed central serous chorioretinopathy after prolonged treatment with glucocorticoids applied locally to the skin [10].
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A 32-year-old man complained of reduced vision and metamorphopsia in the right eye. Best-corrected visual acuity was 20/25 in right eye and 20/20 in left eye. The left fundus was normal but in the right eye there was a well-circumscribed, shallow, serous detachment of the sensory retina. The clinical appearance was consistent with central serous chorioretinopathy, and the diagnosis was confirmed by fluorescein angiography, which showed a leakage point at the superior macula, spreading slowly in an inkblot configuration into the subretinal space. He had seborrheic dermatitis involving the central face, eyebrows, eyelids, and scalp for 2 years treated with topical hydrocortisone acetate cream 1%. After the initial prescription, he used the cream without further medical consultation when his symptoms got worse and used it for 4 weeks, 3–4 times a day before developing central serous chorioretinopathy.
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A 37-year-old man developed blurred vision in the left eye. He had central serous chorioretinopathy in the contralateral eye 5 years before, for which he had been treated with laser photocoagulation. Best-corrected visual acuity was 20/20 in each eye. There were scars from previous laser photocoagulation at the superior macula in the right eye. In the left eye there was a well-delineated area of serous detachment temporal to the fovea and small yellowish precipitates at the posterior aspect of the detached retina. Fluorescein angiography showed a leakage point at the upper pole of the detachment. He had pityriasis versicolor, for which he had used local diflucortolone valerate cream 0.1% in combination with isoconazole nitrate 1%. He had used the cream occasionally but had used it for 3 weeks before the onset of symptoms. He also used diflucortolone valerate cream 0.1% during the first episode of central serous chorioretinopathy.
Three patients developed advanced glaucoma while using topical facial glucocorticoids. Two other patients developed ocular hypertension secondary to topical facial glucocorticoids [11]. Glaucoma and ocular hypertension have been reported after dermal application of glucocorticoids for facial atopic eczema [12]. Glaucoma has also been reported after the use of a glucocorticoid ointment in a young boy [13].
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A 6-year-old boy underwent a resection of levator palpebrae superioris for congenital blepharoptosis. Postoperatively, an ointment containing 0.1% dexamethasone and neomycin (Maxitrol) was applied to the operated eyelid three times a day to reduce lid edema. Four days later the surgical correction was satisfactory and there were no symptoms, but the intraocular pressure was raised to 44 mmHg in the operated eye, although normal in the other eye. The glucocorticoid was withdrawn and topical ocular hypotensive agents were prescribed. The intraocular pressure returned to normal the next day, and the antiglaucoma treatments were maintained for 1 week and tapered over the next 2 weeks. Subsequent follow-up confirmed normal intraocular pressure and no glaucomatous damage.
The ocular hypertensive response in this case could have been due to systemic absorption of glucocorticoid through the skin of the eyelid, especially when there was a surgical wound. Alternatively, a sufficient amount of ointment could have seeped over the eyelid margins, causing the rise in intraocular pressure, similar to the application of eye-drops.
Skin
Although glucocorticoids are used to treat eczema, they can sometimes cause or exacerbate it.
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A 74-year-old man developed worsening eczema 24 hours after he applied clobetasol (Decloban) to treat chronic eczema of his external ear [22]. Twelve years earlier he had noted exacerbation of a cutaneous lesion after he had applied a topical glucocorticoid. He had also had generalized erythema after an intra-articular injection of paramethasone. Patch tests to a series of glucocorticoids were positive for all drugs except flupametasone, fluocortine, and tixocortol. In addition, intradermal tests were positive to hydrocortisone and prednisolone, despite negative patch tests.
The authors commented that most glucocorticoid-sensitized patients react to several of the same group and less frequently of different groups. No case of hypersensitivity to glucocorticoids of all four classes has previously been reported.
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Chronic lichenified eczema has been attributed to prolonged use of topical methylprednisolone aceponate and budesonide (strength and duration of therapy not stated) in a 26-year-old woman [23]. Patch tests were positive for methylprednisolone aceponate and budesonide cream, but negative for all other topical glucocorticoids.
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An 18-year-old woman presented with a pruritic eczematous eruption that developed after topically applying an ointment containing hydrocortisone acetate, neomycin sulfate, and Centella asiatica [24]. She was positive to all three ingredients of the ointment.
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Substances that affect the skin: Contact allergy
In Meyler’s Side Effects of Drugs (Sixteenth Edition), 2016
Anogenital contact allergy (Table 2)
Contact allergy should always be suspected in patients with anogenital dermatitis, especially if the perianal area is involved. In patients with other chronic inflammatory diseases of the anogenital region, for example lichen sclerosus, contact allergy should also be excluded, since long-term use of topical medicaments on compromised skin carries an increased risk of sensitization.
Table 2. The most frequent allergens among patients with anogenital complaints
| Allergen | Number tested | Number with a positive reaction (%)1 | Number with a positive reaction (%)2 | IVDK total 1992–7 (%)3 |
|---|---|---|---|---|
| Nickel sulfate | 962 | 86 (8.9) | 12.6 | 16–17 |
| Balsam of Peru | 962 | 74 (7.7) | 6.6 | 6.5–8 |
| Fragrance mix | 960 | 71 (4.7) | 7.2 | 10–13 |
| Cinchocaine HCl (dibucaine HCl) | 592 | 50 (4.8) | 7.4 | * |
| Thiomersal | 961 | 48 (5.0) | 5.6 | 5–7 |
| Methyldibromoglutaronitrile/2-phenoxyethanol | 958 | 39 (1.4) | 3.1 | 2–3 |
| Paraphenylenediamine | 959 | 39 (1.4) | 3.7 | 4–5.5 |
| (Chloro)methylisothiazolinone | 951 | 32 (3.4) | 3.7 | ~ 2.5 |
| Benzocaine | 962 | 31 (2.3) | 2.7 | ~ 1.5 |
| Phenylmercuric acetate | 736 | 28 (3.8) | 4.0 | 4–8 |
| Neomycin sulfate | 962 | 23 (2.4) | 2.1 | ~ 2.5 |
| Wool wax alcohol | 962 | 22 (2.3) | 2.1 | 2.5–4 |
| Amerchol L-101 | 561 | 21 (3.7) | 2.9 | * |
| Colophony (rosin) | 961 | 19(2.0) | 2.3 | 2.5–3.5 |
| Mercury amide chloride (ammoniated mercury) | 962 | 19(2.0) | 1.7 | ~ 2.5 |
| Propolis | 598 | 17(2.8) | 2.5 | * |
| Parabens mix | 962 | 17(1.8) | 1.6 | ~ 1.5 |
| Benzoylperoxide | 218 | 15(6.9) | 7.6 | * |
| Octylgallate | 560 | 15(2.7) | 2.8 | * |
| Methyldibromoglutaronitrile | 508 | 14(2.8) | 2.1 | * |
| Cobalt chloride | 960 | 13(1.4) | 2.0 | 4.5–5 |
| Propylene glycol | 744 | 12(1.6) | 1.5 | * |
| Formaldehyde | 961 | 12(1.2) | 1.5 | ~ 2 |
| Hexylresorcinol | 476 | 11 (2.3) | 2.1 | * |
| Para-tert-butylphenol | 955 | 11 (1.2) | 1.4 | ~ 1 |
| Formaldehyde resin (PTBP-FR) | ||||
| Thiuram mix | 961 | 11(1.1) | 1.1 | ~ 2.5 |
All allergens that led to positive reactions in more than 1% of the total population (that is 10 patients) are listed.
- 1
- Percentage of positive reactions.
- 2
- Age- and sex-standardized frequency of sensitization.
- 3
- Range of the age- and sex-standardized frequency of sensitization in all patients tested (n=54 500).
- *
- Allergens were tested in selected patients only; so a comparison in this way makes no sense.
Source: IVDK 1992–7 (n = 1008) [21].
In a survey of patch test results in 1374 patients with anogenital dermatoses, of whom 179 (13%) had previous or current atopic dermatitis, allergic contact dermatitis was diagnosed in 409 (30%) [19]. Patients with anal disease had significantly higher sensitization rates for bufexamac (9.4 versus 1.1%), fragrance mix I (8.7 versus 4.2%) and II (4.5 versus 2.6%), propolis (5.4 versus 1.9%), and methyldibromoglutaronitrile (6.3 versus 4.1%).
Patch tests in patients with anogenital eczema should include the standard series: cinchocaine HCl, propolis, bufexamac, and other ingredients of topical formulations according to the patient’s history. In cases of doubt, the repeated open application test (ROAT) is recommended. Patients should be advised to apply the suspected product three times a day for 3 days to an area of healthy skin on measuring 5 cm × 5 cm the flexural site of the forearm [20].
Anesthetics, local
Topical local anesthetics play an important role in anogenital contact allergy [21–25]. Cinchocaine is commonly used in topical antihemorrhoidal formulations and is a well-known sensitizer [26]. Although benzocaine is not as widely used in topical anesthetic formulations in Germany, patients with anogenital dermatitis were at higher risk of sensitization. Amide-type local anesthetics, like lidocaine HCl and tetracaine, are less potent sensitizers [27]. Contact allergy to local anesthetics is more often observed among patients with perianal complaints than patients with perianal and vulval or only vulval dermatitis [23].
Antibiotics
Topical antibiotics are often used in the treatment of dermatitis with bacterial superinfection. However, in Germany sensitization to the aminoglycoside antibiotic neomycin was less frequent in patients with anogenital dermatitis [21] compared with the UK, where 15 of 79 patients with positive patch tests and anogenital complaints were positive to neomycin [23]. Framycetin contact sensitivity was frequent in the UK, partly through cross-reactivity with neomycin [22].
Antifungal drugs
Antifungal drugs are comparatively rare contact allergens in the anogenital region in relation to their widespread use. Clotrimazole and nystatin are preferred. In the study of the IVDK, patch tests with clotrimazole were performed in only 272 patients, leading to five positive reactions [21]. In the UK study on anogenital dermatosis, five women out of 201 patients tested had positive reactions to antifungal drugs, but was unfortunately not specified in the article [23]. If sensitization to nystatin is suspected, polyethylene glycol should be used as a vehicle for patch-testing [28]. Imidazoles can cross-react with one another and most cases of contact allergy occurred with miconazole, econazole, tioconazole, and isoconazole [29].
Condoms
Contact allergy from rubber additives in condoms is sometimes suspected, and there are anecdotal reports [30]. However, in a study of the IVDK, condoms were patch-tested in 17 patients without positive results [21].
Glucocorticoids
Glucocorticoid contact allergy is well known [31] and has to be particularly suspected in chronic conditions affecting the perianal area [23], after long-term topical medication, and in cases of failure to ameliorate dermatitis with glucocorticoids. Patch tests should then be performed both with the recommended markers, budesonide (0.1% petrolatum) and tixocortol pivalate (1% petrolatum), and with the patient’s own formulations.
Nickel
Although sensitization to nickel sulfate (also covered in a separate monograph) is common in patients with anogenital contact dermatitis and in patients with dermatitis in other body sites, the relevance to anogenital complaints of sensitization to nickel sulfate should always be doubted [21,22,32]. However, direct transmission of nickel from the hands to the anogenital region has to be taken into account, and food can be a rare source of nickel contact in the anogenital area. In these cases relevance can be proved by oral nickel provocation and a nickel-restricted diet for a limited period may be justified [33].
Non-steroidal anti-inflammatory drugs
Bufexamac, which has been used in hemorrhoidal formulations, is a non-steroidal anti-inflammatory drug that is a well-known sensitizer and sometimes elicits severe dermatitis [34]. Bufexamac should therefore always be included in patch tests for anogenital dermatitis.
Ointment bases
Ointment bases do not seem to cause contact allergy in the anogenital region too often, despite wide use. Wool wax alcohol and amerchol L-101 are the most important [21,23]. Contact sensitivity to balsam of Peru and fragrance mix is not infrequent and reflects the ubiquitous presence of these substances [22].
Topical remedies are very popular in self-treatment and patients will often not report this, since they do not regard them as medicaments. Furthermore, patients often do not suspect that “natural” remedies cause adverse reactions. Some substances lead to a considerable number of allergic reactions, for example chamomile extract and tincture of Arnica montana [21]. Propolis also has pronounced sensitizing capacity [35], and sensitization to aged tea tree oil is being reported with increasing frequency [36].
Preservatives
Moist toilet paper is a rare source of contact allergens. The most important allergens in moist toilet paper are preservatives, such as CMI/MI and dibromoglutaronitril + 2-phenoxyethanol (Euxyl K 400) [37–39]. These substances were also incriminated in the study of the IVDK (15) and are also found in body care products. In Germany, when CMI/MI was replaced by iodopropyl butylcarbamate (IPBC) in moist toilet paper, one case of contact allergy to IPBC was soon described [40].
Other sources of preservatives are topical medicaments and body care products. Parabens, chloracetamide, and formaldehyde-releasing preservatives, like diazolidinyl urea, imidazolidinyl urea, bronopol, and quaternium 15, should also be considered [21].
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Antifungal azoles and other antifungal drugs for topical use
In Meyler’s Side Effects of Drugs (Sixteenth Edition), 2016
General Information
All the topically used azoles can cause local irritation, burning, and, if used intravaginally, burning, swelling, and discomfort during micturition. There is cross-sensitivity between econazole, enilconazole, miconazole, and probably all other phenethylimidazoles.
Contact allergy to topical imidazoles is rare, considering how commonly they are used. The imidazole derivatives most often reported to be allergens are miconazole, econazole, tioconazole, and isoconazole. As far as cross-reactivity is concerned, in one review, there were statistically significant associations between miconazole, econazole, and isoconazole; between sulconazole, miconazole, and econazole; and between isoconazole and tioconazole [1].
Of 3049 outpatients who were patch-tested for contact dermatitis at the Department of Dermatology, Nippon Medical School Hospital from January 1984 to August 1994, 218 were patch-tested with topical antimycotic agents [2]. There were 66 positive tests with imidazole derivatives, of whom 35 were allergic to the active ingredients: 16 were allergic to sulconazole, 11 to croconazole, 3 to tioconazole, 3 to miconazole, 1 to bifonazole, and 1 to clotrimazole. Exposure to croconazole occurred after a significantly shorter time with less drug than with sulconazole. Of the 35 patients who were allergic to an imidazole, 21 cross-reacted to other imidazoles.
Azoles
Bifonazole
Bifonazole has a broad spectrum of activity in vitro against dermatophytes, molds, yeasts, dimorphic fungi, and some Gram-positive bacteria. It has been used in a strength of 1% in creams, gels, solutions, and powders, applied once a day to treat superficial fungal infections of the skin, such as dermatophytoses, cutaneous candidiasis, and pityriasis versicolor [3]. In a multicenter, double-blind, randomized, parallel-group comparison with flutrimazole cream 1% in the treatment of dermatomycoses in 449 patients the overall incidence of adverse effects (mainly mild local effects such as irritation or a burning sensation) was 5% [4].
Clotrimazole
Clotrimazole was the first oral azole. While it was effective in deep mycoses, its limited absorption and induction of liver microsomal enzymes after a few days, leading to accelerated metabolism of the compound, as well as its toxicity, preclude its use for systemic therapy. Clotrimazole is therefore currently only used for topical therapy of mucocutaneous candidiasis.
Comparisons of fluconazole 200 mg/day with clotrimazole 10 mg 5 times/day in the prevention of thrush in patients with AIDS showed little difference in the occurrence of undesirable effects and abnormalities in laboratory measurements but less efficacy of clotrimazole [5,6].
Local problems can occur, including hypersensitivity reactions [1]. In one case of contact allergy, patch-testing was positive with clotrimazole (5% in petroleum), itraconazole (1% in ether), and croconazole (1% in ether) [7]. The authors reviewed the possible cross-reactions between the subgroups of imidazoles.
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A 71-year-old woman had a severe exacerbation of vulval dermatitis for which she had been using Canesten (clotrimazole) cream [8]. There was a positive patch-test reaction with clotrimazole (1% in petrolatum) and patch tests with the other constituents of Canesten were negative.
Topical vaginal administration of even relatively high doses of clotrimazole did not result in systemic toxicity [9].
Croconazole
In one case of contact allergy, patch-testing was positive with clotrimazole (5% in petroleum), itraconazole (1% in ether), and croconazole (1% in ether) [7]. The authors reviewed the possible cross-reactions between the subgroups of imidazoles.
Econazole
Econazole is used topically on the skin and also intravaginally, after which about 3–7% is absorbed. It can cause pruritus [10] and vaginal burning [11].
Enilconazole
Enilconazole is used in 10% solution/cream. Contact dermatitis has been reported [12,13].
Isoconazole
Isoconazole is mainly used for vaginal infections with Candida albicans. Contact dermatitis has been reported [14], including an unusual case with a papulo-pustular reaction [15].
Itraconazole
In one case of contact allergy, patch-testing was positive with clotrimazole (5% in petroleum), itraconazole (1% in ether), and croconazole (1% in ether) [7]. The authors reviewed the possible cross-reactions between the subgroups of imidazoles.
Lanoconazole (latoconazole)
Used in a 1% cream, lanoconazole is effective against Tinea, and is more active than clotrimazole or bifonazole. Several cases of contact dermatitis have been reported [16–20].
Miconazole
See the monograph on miconazole.
Nimorazole
Nimorazole is believed to be active against Trichomonas vaginalis. No specific adverse effects have been described after local use.
Ornidazole
Complaints of dizziness [21], mild gastrointestinal symptoms [22], and headache [23] during treatment with intravaginal ornidazole have been reported, since ornidazole is relatively well absorbed after rectal and vaginal administration [23].
Terconazole
Terconazole is prepared in creams and ovules for intravaginal use. Besides local irritation it causes systemic reactions. Headache was reported in over a quarter of patients. Other effects include hypotension, fever, and chills. Terconazole is absorbed to a greater extent than other topical azoles [24].
Tioconazole
Tioconazole is mainly used for vaginal or inguinal Candida infections. It has fewer local adverse effects than some of the older imidazoles. Local irritation, burning, rash, erythema, and pruritus have been reported. In a few women there was marked burning on micturition; these women all had signs of vaginal epithelial atrophy [25].
Other topical antifungal drugs
5-Bromo-4-chlorosalicylamide (multifungin)
5-Bromo-4-chlorosalicylamide is one of a group of local antiseptics and fungistatics that can cause photosensitization [26]. There is cross-sensitization with bithionol, fenticlor, and tribromosalicylanide.
Buclosamide (N-butyl-4-chlorosalicylamide)
Photocontact dermatitis has been described with buclosamide [26]. There is cross-reactivity with a number of other drugs, notably oral hypoglycemic drugs, diuretics, and sulfonamides. Because of these reactions, buclosamide is not recommended for topical use.
Captan (Orthocide-406)
Captan is one of the older fungicides. It is used for pityriasis versicolor and is included in some soaps and cosmetics to provide bactericidal and fungicidal effects. It is allergenic. It is carcinogenic in mice, and in several countries control agencies have taken steps to prohibit its use in cosmetics and non-drug products [27].
Ciclopirox
Ciclopirox, a substituted pyridone unrelated to the imidazoles, is effective against a wide variety of dermatophytes, yeasts, actinomycetes, molds, and other fungi. Ciclopirox olamine is generally well tolerated locally, and reactions occur in only 1–4% of cases [28].
Clodantoin
Contact dermatitis has been rarely reported with clodantoin.
Fluonilide (4-fluoro-3′,5′-thiocarbanilide)
Contact dermatitis has been reported with fluonilide [29].
Gentian violet
Gentian violet [30] was at one time the treatment of choice for vaginal and oral candidiasis but is now obsolete. The main problem is staining and the messiness of the application, since the purple-colored fluid has to be brushed on to the skin.
Hachimycin (trichomycin)
Contact dermatitis has been reported with hachimycin.
KP-363
KP-363, a benzylamine derivative, is used in creams and solutions in concentrations of 0.1% and 0.6%. It is reported to cause less irritation than bifonazole and tolciclate [31].
Naftifine
Naftifine is one of a series of allylamine antifungal agents, derived from heterocyclic spironaphthalenes. It is usually sold in the form of a 1% cream for topical treatment of dermatomycoses, dermatophytes, and yeasts. It is claimed to be more effective than the imidazoles. Local irritation and a burning sensation, if they occur, are only mild [32,33].
Natamycin (pimaricin)
No cases of contact dermatitis were described in industrial workers in frequent contact with natamycin [34].
In the Hungarian Case–Control Surveillance of Congenital Abnormalities between 1980 and 1996, of 38 151 pregnant women who delivered infants without any defects (controls) and 22 843 who had fetuses or neonates with congenital abnormalities, 62 (0.27%) and 98 (0.26%) were treated with vaginal natamycin in the two groups respectively (crude OR = 1.1; 95% CI = 0.8, 1.5). There was thus no evidence of a teratogenic effect of natamycin.
Nifuratel
Contact dermatitis, with facial edema and a generalized erythema, has been described in the partner of a woman treated with nifuratel vaginal suppositories [35].
Niphimycin
Niphimycin, an antimycotic antibiotic derived from Actinomyces hygroscopicus, is effective against both dermatomycosis and onychomycosis, with a 16–26% success rate in the latter. Tolerance is reportedly good, but there is a notable lack of recent data [36].
Nystatin
See the monograph on Nystatin.
Pecilocin (Variotin)
Skin irritation has been reported in 2–6.5% of patients treated with pecilocin. Contact dermatitis has been described in a few cases [37,38]. Of 44 patients treated with pecilocin who were patch-tested with pecilocin, seven were allergic to it; in three of them the skin disease had been caused or exacerbated by pecilocin [39].
Pyrrolnitrin (miutrin, 3-chloro-4-(3-chloro-2-nitrophenyl) pyrrole)
Contact dermatitis with pyrrolnitrin and cross-reactivity with dinitrochlorobenzene has been reported in one case [40].
Salicylic acid 3% with benzoic acid 6% (Whitfield’s ointment)
Whitfield’s ointment, used for Trichophyton rubrum, has a keratolytic effect, and local irritation can occur [41].
Sulbentine (dibenzthion)
Photoallergic contact dermatitis has been described with sulbentine, probably through a breakdown product, benzylisothiocyanate [42].
Tolciclate
Tolciclate, a thiocarbamate, is active against most common dermatophytes. Contact dermatitis has been reported [43].
Tolnaftate
Tolerance of tolnaftate is good. Local erythema has been described, as has allergic dermatitis [44].
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URL:
https://www.sciencedirect.com/science/article/pii/B9780444537171003127
Dermatophytosis (Ringworm) and Other Superficial Mycoses
Roderick J. Hay, in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (Eighth Edition), 2015
Therapy
The usual approach to the management of dermatophyte infections is topical therapy if possible, but most nail and all hair infections and widespread dermatophytosis are best treated with oral drugs (Table 268-3).36
The main topical agents used for dermatophytosis are compounds with specific antifungal activity. The keratolytic agents such as Whitfield’s ointment (salicylic and benzoic acid compound) are sometimes used. Currently, a large group of specific antifungal agents are used in treatment of dermatophytosis, although some of these are largely confined to the treatment of tinea pedis. The most frequently used medications are the topical azole antifungal agents, which include miconazole, clotrimazole, econazole, tioconazole, ketoconazole, oxiconazole, bifonazole, and isoconazole.37 These are active against all the common skin fungi, and many can be taken once daily. Other potent topical antifungal agents used in the treatment of dermatophytosis are ciclopirox olamine, terbinafine, butenafine, and naftifine. It is difficult to choose between the different groups of these agents on the basis of well-constructed comparative studies. In addition, older preparations, such as chlorphenesin, undecylenate, and tolnaftate, are available in cream or, in some cases, powder form and are effective in uncomplicated cases.
In general, topical therapy for tinea pedis has to be continued for at least 2 and possibly 4 weeks. Topical terbinafine can be used to clear lesions of tinea pedis in 7 days and is also available as a single-dose film-forming solution applied to the soles of the feet. Tinea cruris usually responds within 2 or 3 weeks of the outset of treatment. Some of the azole agents can be used only once daily. Topical treatments for scalp and nail infections are generally ineffective, although cures of nail disease have been claimed for topically applied azoles. Three other preparations are of potential value in the management of nail disease. The first, a topically applied nail solution containing 28% tioconazole, has been found to produce some mycologic and clinical remissions. The second preparation is a combination of 40% urea and bifonazole. Urea is a potent hydrating agent and softens nails after application under occlusion. The 40% urea paste may be used to remove residual areas of infection after oral therapy for onychomycosis.38 This combination may also prove useful in addition to oral therapy for nail disease. Third, solutions with penetration enhancers, such as ciclopirox olamine and amorolfine, are more widely used as nail lacquers. They are effective in a proportion of early cases of dermatophyte and Candida nail infection. They are applied once or twice weekly and increasingly used as combination therapy with oral drugs in severe infections.39
The main oral antifungal agents used for dermatophytosis are terbinafine, itraconazole, and fluconazole. Griseofulvin is an older alternative treatment but is still used in some cases of tinea capitis. Terbinafine is given in dosages of 250 mg daily for 2 weeks for tinea cruris or corporis, 6 weeks for fingernail infections, and 12 weeks for toenail infections. It produces rapid and long-lasting remissions for dry-type dermatophytosis and other skin infections. Itraconazole can be given continuously in dosages of 200 mg daily and is curative for tinea cruris or corporis after 1 week. It is given as a pulsed treatment in toenail onychomycosis (see later). Fluconazole can also be used as a treatment for dermatophytosis, but current regimens entail 150 to 300 mg weekly for infections of the skin. All three drugs are well tolerated and involve a low risk for hepatic injury (<1 per 70,000); in rare instances, terbinafine causes disturbance or loss of taste. All show evidence of efficacy.40,41
Griseofulvin is given in dosages of 10 to 20 mg/kg daily for the microsize formulation in either tablet or syrup form and is still used in the treatment for tinea capitis. Adverse effects include headache, nausea, and abdominal discomfort. Less common reactions are urticaria, diarrhea, and photosensitivity. Newer triazoles such as posaconazole, voriconazole, pramiconazole, and albaconazole are still under assessment in dermatophytosis but are not widely used. Oral therapy is used for scalp ringworm and nail infections. Scalp infections take 6 to 12 weeks to respond to oral antifungal agents. It is often useful to use a topical azole cream or shampoo in addition and, if crusts are present, to remove these with saline soaks. Itraconazole and terbinafine are also effective in treating scalp disease, and pediatric formulations are available in some countries.42 Terbinafine is effective against Trichophyton scalp infections but less active against Microsporum, for which a double dosage is advised; treatment is for 4 weeks. It is important to attempt to identify the organism causing scalp infection because, if the infection is of human origin, it can spread to other contacts, and it may be necessary to screen classmates or members of the families of children with anthropophilic infections. Zoophilic infections do not usually spread from child to child, although several family members exposed to the same source of infection may develop scalp disease.
Onychomycosis caused by dermatophytes can be treated with oral therapy. Terbinafine and itraconazole have replaced griseofulvin for this indication. For instance, in 70% to 80% of patients, terbinafine produces cure in 6 weeks for fingernails and 12 weeks for toenails.43 Itraconazole is also effective against toenail infections at a dose of 200 mg daily for 3 months. However, for nail infections, it is usually administered as a “pulsed” treatment given for 1 week of each month at a dosage of 400 mg daily, the week’s course being repeated once more for fingernail infections (two pulses) and twice or three times for toenail disease (three or four pulses).44 Reported remission rates are above 60%. Intermittent regimens with fluconazole (300 and 450 mg weekly) are used in the treatment of onychomycosis.45 There have been no large comparative studies of fluconazole versus the other two treatments for nail disease. However, in one large double-blind study of patients with toenail onychomycosis, terbinafine, given continuously at 250 mg daily for 12 or 16 weeks, was compared with pulsed itraconazole, at 200 mg twice a day for 1 week each month repeated three or four times. The results revealed significantly better responses for both terbinafine groups than for itraconazole in both mycologic and clinical remission rates.46 To date, in vitro resistance to drugs used in dermatophytosis has not proved to be a significant problem.
The U.S. Food and Drug Administration has approved several short-pulse laser systems for treatment of onychomycosis. The intent is for near-infrared light given over 15 to 30 minutes to kill fungi in the nail and nail bed. One to four treatments are used, separated by several weeks. Treatment is expensive and relative efficacy not established.47
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Описание активного компонента
Фармакологическое действие
Противогрибковое средство для наружного и местного применения. Действует фунгистатически на дерматофиты, дрожжеподобные и плесневые грибы. Активен в отношении Corynebacterium minutissimum и некоторых грамположительных бактерий.
Показания
Все виды дерматомикозов, в т.ч. вторично инфицированные; кандидоз; эритразма. Инфекционно-воспалительные заболевания влагалища, вызванные чувствительными к изоконазолу возбудителями.
Режим дозирования
Наружно наносят на пораженные участки кожи 1 раз/сут. Курс лечения составляет не менее 4 недель. Во избежание рецидива необходимо продолжить лечение еще 2 недели после клинического выздоровления. Интравагинально применяют 1 раз/сут вечером перед сном.
Побочное действие
Редко: раздражение, легкое жжение, аллергические кожные реакции.
Противопоказания
Повышенная чувствительность к изоконазолу.
Особые указания
Следует избегать попадания изоконазола в глаза. Интравагинально не применяют в период менструации.
Травоген — инструкция по применению
Синонимы, аналоги
Статьи
ИНСТРУКЦИЯ
по медицинскому применению препарата
ТРАВОГЕН
П N014590/01
Торговое название: Травоген
Международное непатентованное наименование:
изоконазол
Химическое название: 1-[2,4-Дихлор-бета-[2,6-дихлорбензол)]-фенетил]имидазол
Лекарственная форма: крем для наружного применения 1%
Описание: Белый или слегка желтоватого цвета непрозрачный крем.
Состав:
В 1 г крема содержится:
активное вещество: изоконазола нитрат 10 мг,
вспомогательные вещества: сорбитана моностеарат, полисорбат 60, кетостеариловый спирт, жидкий парафин, светлый сухой парафин, вода очищенная.
Фармакотерапевтическая группа:
противогрибковое средство.
Код АТС D01АС05
Фармакологическое действие
Изоконазол – синтетическое производное имидазола. Оказывает местное противогрибковое и антибактериальное действие. Действует фунгистатически. Активен в отношении дерматофитов Trychophyton, Microsporum, Epidermophyton, плесневых, дрожжевых и дрожжподобных грибов, а также Corynebacterium minutissium — возбудителя эритразмы и некоторых граммположительных бактерий (сирептококки, стафилококки). При нанесении на кожу системная абсорбция незначительна.
Показания к применению
Грибковые поражения кожи, в том числе вторично инфицированные:
— дерматомикозы стоп и кистей, гладкой кожи, головы, крупных складок, области наружных половых органов
— эритразма
Противопоказания
Повышенная чувствительность к компонентам препарата.
Способ применения и дозы
Травоген наносят на поражённые участки и слегка втирают; процедуру проводят 1 раз в день. Курс лечения обычно составляет не менее 2-3 недель, а в рефрактерных к терапии случаях ( в частности , при поражении межпальцевых пространств) – до 4 недель. Возможно проведение и более длительного курса лечения. Для предотвращения рецидива после разрешения клинических проявлений лечение следует продолжить ещё в течение 2 недель.
Побочное действие
Обычно Травоген переносится хорошо , даже при нанесении на чувствительную кожу. Иногда может развиться раздражение (ощущение жжжения и зуда, эритема), в редких случаях – кожные аллергические реакции. Если после применения препарата возникнут побочные эффекты, которые не указаны в данной информации, то пациенту следует сообщить о них врачу.
До настоящего времени сведений о передозировке не имеется. В связи с низкой токсичностью изоконазола нет оснований ожидать риска острой интоксикации после разового применения препарата в высокой дозе или непреднамеренного приёма препарата внутрь.
Взаимодействие с другими лекарственными средствами
Клинические испытания и применение препарата в медицинской практике не выявили несовместимости или взаимодействия с другими лекарствами.
Рекомендуется информировать врача об одновременном лечении другими лекарственными препаратами.
Меры предосторожности и предупреждения
Препарат используется только для наружного применения. При отсутствии эффекта в указанные сроки терапии пациенту следует обратиться к врачу. При появлении первых симптомов, свидетельствующих о повышенной чувствительности или раздражении, препарат необходимо отменить.
Следует избегать попадания препарата в глаза.
Беременность и период кормления грудью
Клинический опыт использования содержащих изоконазол препаратов во время беременности не даёт указаний на то, что они вызывают риск тератогенности у человека. Маловероятно, что при накожном применении изоконазол в эффективных количествах может попадать в грудное молоко.
Применение в педиатрии
Детям до двухлетнего возраста препарат назначают только по строгим показаниям и под контролем врача.
Форма выпуска:
Крем для наружного применения 1% в тубах по 20г
Условия хранения
В сухом. защищеном от света месте при температуре не выше 30°С.
Хранить в местах, недоступных для детей.
Срок годности
5 лет.
Не использовать по истечении срока годности
Условия отпуска из аптек
По рецепту врача.
Производитель
Интендис ГмбХ, Германия, произведено, Интендис Мануфэкчуринг СпаА, Италия
10589, Берлин, Макс Дорн Штрассе 10, Германия
Ул. Э.Шеринга, 21 20090 Сеграте Милан, Италия
Дополнительную информацию можно получить по адресу: .107113 Москва, 3-я Рыбинская ул., д.18., стр. 2.
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