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ANTI HISTAMINES Receptor Distribution Response H1 Smooth Muscle Endothelium Brain H2 Gastric Mucosa Cardiac Tissue Mast Cells Brain H3 Presynaptic: Brain, Myenteric plexus H4 Eosinophils, Neutrophils, CD4-T cell H 1 -receptor antagonists It has been discovered that these H 1 -antihistamines are actually inverse agonists at the histamine H 1 -receptor, rather than antagonists per se. All H1 antagonists are reversible, competitive inhibitors of histamine receptors. Some of the first-generation H1-receptor blockers (eg, diphenhydramine, clemastine, promethazine) are also potent competitive inhibitors of muscarinic receptors and may cause anticholinergic syndrome (eg, sinus tachycardia, dry skin, dry mucous membranes, dilated pupils, ileus, urinary retention, agitated delirium). H1-receptor blockers may disrupt cortical neurotransmission and block fast sodium channels. These effects can exacerbate sedation, but they also can result in seizure activity.
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Page 1: AntiHistamines

ANTI HISTAMINESReceptor Distribution Response

H1Smooth MuscleEndothelium Brain

H2

Gastric MucosaCardiac TissueMast CellsBrain

H3 Presynaptic: Brain, Myenteric plexus

H4 Eosinophils, Neutrophils, CD4-T cell

H1-receptor antagonists

It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se.

All H1 antagonists are reversible, competitive inhibitors of histamine receptors.

Some of the first-generation H1-receptor blockers (eg, diphenhydramine, clemastine, promethazine) are also potent competitive inhibitors of muscarinic receptors and may cause

anticholinergic syndrome (eg, sinus tachycardia, dry skin, dry mucous membranes, dilated pupils, ileus, urinary retention, agitated delirium). H1-receptor blockers may disrupt

cortical neurotransmission and block fast sodium channels. These effects can exacerbate sedation, but they also can result in seizure activity.

Page 2: AntiHistamines

First-generation Brand Name Dosis Indikasi KontraIndikasi Efek Samping

Page 3: AntiHistamines

ETHANOLAMINES

Carbinoxamine

Kenantist Tab.100mg

(Triamcinolone 1.25 mg, Carbinoxamine maleate 2 mg)

1-2 tab 3-4 x/hr. a.Dermatosis alergi, urtikaria, pruritus.

b. Asma bronkial.

c.Hay fever.

d. Rinitis vasomotor & konjungtivitis alergi

TBC aktif. Herpes simpleks okuler. Psikosis aktif. Ulkus peptikum. Glomerulonefritis akut. Infeksi akut. Divertikulitis. Anastomosis intestinal

baru. Tromboflebitis. Karsinoma metastasis. Osteoporosis.

Ggn sal cerna. Efek anti muskarinik. Reaksi alergi. Ggn darah. Ggn metabolisme. Penyembuhan luka terlambat, peningkatan kecenderungan

infeksi. Wajah spt bulan (moon face), hirsutisme, punuk kerbau (buffalo hump), kemerahan muka, luka memar, striae, akne. Amenorea, hiperhidrosis. Ggn neurologi.

Dimenhydrinate (salt of diphenhydramine)

Dramamine Tab.50mg Dosis awal : 30 menit sebelum bepergian.

Dws: 50-100mg (3-4x/hr)

(2-3x.hr) ≥12thn: 50mg 8-12thn : 25-50mg 6-8 thn : 12,5-25mg

To prevent and treat nausea, vomiting, dizziness, and vertigo associated with motion sickness.

Menganttuk

Diphenhydramine

Arcodryl®[vial 10mg/10 ml] (Diphenhydramine HCl) 10-50 mg IM daily.

Delladryl (Diphenhydramine HCl inj.10mg/ml x 10ml)

hay fever, allergic rhinitis,conjunctivitis, urticaria,angioedema, serum sickness,atopic & contact

dermatitis.

Premature or newborn infants.

Acute asthmatic attack.

Sedation. GI disturbances.Antimuscarinic effects. Hypotension, muscular weakness, tinnitus, euphoria, headache. CNS stimulation. Allergic reaction.

Blood disorder

Page 4: AntiHistamines

First-generation Brand Name Dosis Indikasi KontraIndikasi Efek Samping

ETHYLAMIDEDIAMINE

Tripelennamine

Tripel. cream 2% x

12.5g

(Tripelennamine HCl)

Oleskan jika

dibutuhkan

Alergi kulit, gatal,

gigitan serangga,

tersengat matahari

PIPERAZINE derivates

Hydroxyzine

Bestalin

(hydroxyzine HCl)

Tab.25mg.

Sir.10mg/5ml x 100ml

Dws:25mg(3x/hr)

[terbagi dlm 3-4 dosis

>6thn : 50-100mg/hr

<6thn : 50mg/hr

Pruritus krn alergi

(urtikaria kronik,

D.atopik&D.kontak),

meredakan ansietas.

Mengantuk

Cyclizine

Meclizine

ALKYLAMINES

Brompheniramine

Chlorpheniramine

Chlor-Trimeton,

CTM(Chlorpheniramine

maleat tab.4mg)

PHENOTHIAZINE derivate

Promethazine

Phenergan

(Promethazine HCl

tab.25mg)

Miscellaneous

Cyproheptadine Apeton (Kapl.salut selaput

4mg)

Rhinitis alergi,

urtikaria, angioudema.

Page 5: AntiHistamines

Cylat, Esprocy

(Kapl.4mg)

Ennamax, Poncohist

(Tab.4mg)

Glocyp, Heptasan

(Tab.salut selaput 4mg)

Pronicy (Kapl.salut gula

4mg)

Second-generation Brand Name Dosis Indikasi KontraIndikasi Efek Samping

PIPERIDINE

Fexofenadine Fenofenadine HCl

Telfast tab.salut

selaput 30 mg.

Telfast BD/OD/HD

Tab BD 60mg

Tab.salutslptOD120mg

Tab.salutslptHD180mg

Anak 6-11thn: 30mg

(2x/hr)

Dws&anak≥12thn :

BD 1tab.2x/hr.

OD&HD 1x1tab.

Rhinitis allergic

Rinitis alergik,

urtikaria idiopatik

kronik

Miscellaneous

Loratadine Tab.10mg Dws&anak≥12thn : 1tab/hr atau 2sdt/hr.

Anak 6-12 thn (BB>30kg : 1tab,2sdt) (BB<30kg : ½tab,1sdt) -1x/hr

Meringankan gejala rinitis alergi, spt bersin2,rinorhea, gatal pd hidung,, gatal&terbakar pd mata.

Hipersensitif thd loratadine

Tab.10mg [Alernitis, Allohex, Alloris, Clarihis, Lorapharm, Loratadine hexpharm

Tab.salut selaput 10mg [Anlos

Sir. 5mg/5ml x 60ml [Allohex, Loratadine hexpharm

Claritin/Claritin effervescent – loratadine micronized – tab.10mg, Sir. 5mg/5ml x 30ml (60ml), Tab. Effervescent 10mg

Page 6: AntiHistamines

Cetirizine Tab. 10mg 10mg/hari

Cetirizin diHCl

Tab.10mg [Betarhin,

Kapl.salut selaput 10mg [Cerini

Tab.salut selpaut 10mg[Cetirizine hexpharm, Cetirizin OGB, Cetrixal, Risina, Tiriz

Tetes 10mg/ml x 20ml - Tiriz

Sir.5mg/5ml x 60ml : Risina

Incidal OD – kaps.10mg, Sir.5mg/5ml x 60ml

Dosis : dws&anak≥12thn (1kaps atau 2sdt), anak 6-12thn (2sdt), 2-6thn – BB<30kg : 1sdt, 1-2thn (1/2 sdt). Semua dosis- 1x/hr.

H2 receptor antagonists tidak dibahas

block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells.

H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective proton pump inhibitors. In

the United States, all four FDA-approved members of the group—cimetidine, ranitidine, famotidine, and nizatidine—are available over the counter in

relatively low doses.

Pharmacology

The H2 antagonists are competitive antagonists of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells

and the meal-stimulated secretion of acid.

They accomplish this by two mechanisms: Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors, which

stimulate acid secretion; therefore, other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells

when the H2 receptors are blocked.

Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists.

Clinical use

Peptic ulcer disease (PUD)

Gastroesophageal reflux disease (GERD/GORD)

Dyspepsia

Prevention of stress ulcer (a specific indication of ranitidine)

People that suffer from infrequent heartburn may take either antacids or H2-receptor antagonists for treatment. The H2-antagonists offer several advantages over antacids,

including longer duration of action (6–10 hours vs 1–2 hours for antacids), greater efficacy, and ability to be used prophylactically before meals to reduce the chance of

heartburn occurring. Proton pump inhibitors, however, are the preferred treatment for erosive esophagitis since they have been shown to promote healing better than H2-

antagonists.

H2 antagonists are, in general, well-tolerated, except for cimetidine, wherein all of the following adverse drug reactions (ADRs) are common. Infrequent ADRs include

hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhea, constipation, and rash.[1] In addition, cimetidine may also cause gynecomastia in

males, loss of libido, and impotence, which are reversible upon discontinuation.

H3 receptors anatgonist

H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine.

Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral

cortex. Consequently unlike the H1 antagonist antihistamines which are sedating, H3 antagonists have stimulant and nootropic effects, and are being researched as potential

drugs for the treatment of neurodegenerative conditions such as Alzheimer's disease.

Examples of selective H3 antagonists include clobenpropit, ciproxifan.

H4 receptors antagonist

Immunomodulator Antiinflamation & analgesic Thioperamide

Page 7: AntiHistamines

Fungal Nail Infections (Onychomycosis)

Fungal infection of the nails is most common. They crop up in places where heat,

humidity and activities require communal bathing.

Seen in approximately 45 per cent of the general population, and in nearly 50 per

cent in people over age 70. Nail infections are rare in children.

Did you know that toenails are seven times more likely to be involved than

fingernails?

Watch out for these top ten risk factors:

Communal bathing

Saunas

Spas

Sporting activities

Closed footwear

Damaged nails by trauma

Conditions changing nails e.g. Psoriasis

Genetic susceptibility

Diabetes

Peripheral vascular disease (damage or dysfunction near the surface of

arteries and veins)

What causes nail infections?

50 to 70 per cent are caused by Dermatophytes (T rubrum)a parasitic fungus

that affects the skin, hair, or nails

5 to 17 per cent is caused by a fungus called T mentagraphytes

Less than 5per cent are caused by parasitic fungi, such as Candida and

molds

Why do I keep getting Candida infections?

If you are sick, elderly, or very young, you are more prone to getting infection. Food

and debris in the mouth encourage Candida, as seen in Sjögren's disease, which

reduces saliva flow.

If you have the following you are at risk for Candida:

psoriasis and/or eczema

iron deficiency

using oral, topical or inhaled steroids

Diabetes and Cushing's disease

immunosuppressed with T-cell function depression such as HIV/AIDS

if you have any number of endocrine (relating to glands that secrete

hormones internally directly into the lymph or bloodstream) conditions

including Addison's disease, hypothyroidism and hypoparathyroidism

There is also a condition called Chronic Mucocutaneous Candidiasis that

allows growth of Candida.

Treatments for Skin, Nail and Hair Infections

Athletes foot

General advice as posted in the Prevention section

Topical antifungal creams once or twice a day for 2-4 weeks. Continue for at least 2 weeks after clearing and intermittently thereafter.

Anti-sweating treatment may be of value to those who sweat a great deal (e.g., Drysol® )

Page 8: AntiHistamines

Topical corticosteroid should only be used if there is a fast secondary eczematous (eczema-like) reaction, and used only in combination with the topical antifungal preparation.

Systemic therapy should be considered if the athletes foot infection features:

-   If your toe nails are also involved-   If its severe Moccasin type (fine scales on the soles of your feet with some redness)-   If you do not respond to topical therapy

Jock itch (groin infection)

General advice as posted in the Prevention section Topical antifungal cream is usually sufficient. Apply on the affected area and

4-6 cm on the surrounding skin Use for 2 weeks after the rash has gone Also treat your feet if there is evidence of fungus infection If the infection spreads to the buttocks and/or abdomen, topical applications

may prove difficult; consider oral antifungal drugs instead

Ringworm (skin infection)

Localized infection Topical antifungal cream is usually sufficient. Apply on the affected area and

4-6 cm on the surrounding skin Use for 2 weeks after the rash has gone If the infection is extensive, and therefore makes topical applications difficult,

oral antifungal drugs may be the best method If fungal culture indicates that the fungus is animal in origin, a veterinarian

should be consulted

Nail infection

If your nail changes are asymptomatic (you have no symptoms), you may decide against treatment after weighing the risks. In the past prolonged oral treatment was the only option. For early nail fungal infection a new penetrating antifungal lacquer has provided another alternative with no risk of systemic side effects.

Patients who have diabetes or peripheral vascular disease may be at increased risk of developing complications such as secondary bacterial skin infections from having persistent nail or skin fungal infection

Terbinafine is the oral treatment of choice. For the toenails a minimum of 3 months treatment is required, whereas 6 weeks may do for the fingernails. Severe liver reactions have been observed rarely with this drug. It is recommended that LFTs be measured before and one month into treatment. This drug can also alter your ability to taste.

Itraconazole is an alternative drug that can be used. It is effective if there is Candida or in the immunosuppressed patient with non-dermatphyte infection such as Aspergillus. Care must be taken with this drug in those at risk of heart failure, or in the elderly who are on negative inotropic drugs. Liver function tests are recommended if there is a history of liver disease or for treatment periods longer then 1 month . This drug can be taken daily for 1 week out of every month for 3 to 4 cycles.

Ciclopirox Nail Lacquer is a useful product in treating early nail fungus infection. It avoids the risks of oral medication, it is useful when the infection is limited to part of the nail, as well as for the superficial type of infection showing white nail changes. It has also been useful for treatment of chronic paronychia which causes the skin around the nail to become red and mushy, and can give the nail a green tinge

Scalp infection

If your child has a scalp infection, there is no need to stay away from school once they have started treatment

Shampoos containing antifungal ingredients such as Ketoconazole may be helpful in reducing risk of spreading infection.

Prevention of Fungal Infections

Check out these tips …

It's important to understand that although fungal infections are annoying and can cause some discomfort, you don't need to miss school or work. However, care should be taken to minimize skin-to-skin contact with others.

Page 9: AntiHistamines

What to do about skin, nail or hair infections?

Athletes foot

Wear flip-flops in changing areas. Use antifungal sprays or powders in shoes and feet. Dry the feet and between the toes last after a shower to prevent spread to

other parts of the skin. Avoid tight or closed footwear especially in warm climates. Change socks daily. Cotton socks keep the feet cooler. Wash towels daily.

Ringworm (skin infection)

Ringworm on the body can either spread from fungus elsewhere on the skin or from animals. It can also spread from contact with others.

Nail infection

An infected toenail is common but there won't always be symptoms. You may see a thickening of the nail, which can be uncomfortable when it

rubs against footwear. You may also see an infection of the skin, especially the web space between

the outer toes.

Jock itch (groin infection)

Wash the groin daily. Dry the skin carefully after bathing. Do not dry the feet before the groin to reduce the risk of spreading fungus

from the feet. Change underwear daily. Wash towels daily.

Scalp infection

An infection of the scalp would show an increase of fungus. It can be spread to others in the same family, or at school. There is no need to keep children out of school but combs and head wear

should not be shared with other children. There is always a risk of the infection being spread from pets.

Jock itch (groin infection)

Wash the groin daily. Dry the skin carefully after bathing. Do not dry the feet before the groin to reduce the risk of spreading fungus

from the feet. Change underwear daily. Wash towels daily.

Ketoconazole

It was originally developed in the late 1970's in the oral form and granted FDA acceptance in 1981. Shortly after the topical formulations were undergoing trials and proven effective. The 2% cream and 1% shampoo are now available over the counter. It is effective against yeasts and dermatophytes, both systemically and topically. It is now mainly used systemically in treating life-threatening fungal infections

Trade Name:

Nizoral*   Janssen

Dosage Forms:

Topical: Cream: Ketoconazole cream 2% Nizoral* Shampoo: Ketoconazole shampoo 1% and 2% Nizoral Shampoo*

Page 10: AntiHistamines

Oral: Tablets: Ketoconazole tablets 200 mg Suspension: Ketoconazole oral suspension 100mg/5mL Nizoral*

Uses

Labeled Indications Off-Label Uses

Topical

Tinea corporis, cruris, pedis Pityriasis versicolor Cutaneous candidiasis Seborrehic dermatitis Dandruff

Systemic Tinea corporis, cruris, pedis, severe and unresponsive to Griseofulvin therapy

Chromomycosis Chronic mucoutaneous candidiasis Candidiasis, oropharyngeal

Other (selection)

Paracoccidiomycosis Candidiasis, systemic

Systemic

OnychomycosisParonychia # Leishmaniasis, cutaneous # Candidiasis, vulvo-vaginal #

# - not included in Canadian product labeling

 

Therapeutic Regimen

Adult Pediatric

Systemic

Pityriasis versicolor Ketoconazole 200mg po daily x5-10d

Other antifungal indications Ketoconazole 200-400mg po daily.

Therapy to be continued for 1-2 weeks in candidal infections; for 1- 8 weeks in dermatophytes; and for 6 months or longer in systemic mycoses

Systemic

Safety and efficacy have not been established for systemic use in children < 2 years of age

> 2 years of age

Ketoconazole 3.3-6.6 mg/kg po daily

Page 11: AntiHistamines

Topical

Dandruff Ketoconazole 1% shampoo every 3-4 days for up to 8 weeks

Seborrehic dermatitis

Ketoconazole 2% shampoo or cream twice a week for 2-4 weeks. Apply to the hair and scalp, leave for 5 minutes and wash off

Pityriasis versicolor

Ketoconazole 2% shampoo single application to the affected areas and surrounding skin. Leave for 5 minutes and rinse.

Tinea corporis, cruris, pedis and cutaneous candidiasis

Ketoconazole 2% cream applied to the affected areas, and surrounding skin once a day until clear.

Vulvovaginal candidiasis

Ketoconazole 5-10 mg/kg po daily yx5d

Paronychia

Ketoconazole 5-10 mg/kg po daily

Topical

Safety and efficacy have not been established for topical use

Safety Information

Concurrent use with cisapride, aztemizole and terfenadine is contraindicated. Ketoconazole cream contains sulfites to which some patients may be allergic Hepatotoxicity may occur and has led to reported deaths. Ketoconazole may increase serum digoxin concentrations and lead to toxicity.

Side Effects

Local cutaneous effects may include itching, stinging, irritation or contact dermatitis.

Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome

Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.

Hematologic effects may include agranulocytosis or thrombocytopenia.

Other effects may include headache, dizziness and drowsiness. Azospermia, impotence, decreased libido in menstrual irregularities may occur as a result of corticosteroid

and testosterone suppression.

Page 12: AntiHistamines

FDA Pregnancy Category C

Animal studies have shown teratogenicity and embryonic toxicity when given very high oral doses. Use of ketoconazole is not recommended during pregnancy or lactation.

Mechanism of Action / Pharmacokinetics

The azole antifungals interfere with cytochome P450 enzyme activity and inhibit demethylization of 14-alpha-methylsterolsterols to ergosterol. Since ergosterol is essential to the

fungal cell membrane, when it is depleted the fungal cells are destroyed.

Ketoconazole may also interfere with the conversion of lanosterol to cholesterol, affecting steroid hormone synthesis.

Systemic ketoconazole is well distributed, however it does not penetrate the CSF. Topical application does not result in significant systemic absorption.

 Clotrimazole

Azole: a broad spectrum antifungal developed in 1967. It was one of the first azoles to be developed. Formulations are now generic in a number of countries. It is effective against Candida albicans and the dermatophytes. Its action is fungistatic or fungicidal, depending upon the concentration used. This azole drug is available in a variety of dosage forms, including oral lozenges and vaginal formulations. It is also available in a variety of combinations with antibiotics and corticosteroids.

Trade Name:

Canesten* Bayer Mycelex* Bayer Desenex* Novartis

Oral:

Lozenges: Clotrimazole 10 mg Mycelex* Topical: Cream: Clotrimazole 1% Desenex* Lotrimin*

        - Lotion: Clotrimazole 1% Desenex* Lotrimin*        - Solution: Clotrimazole 1% Desenex*

Used for

Tinea corporis Tinea cruris Tinea pedis Pityriasis versicolor Cutaneous candidiasis Nail and skin infections, fungal or gram positive

Page 13: AntiHistamines

Therapeutic Regimen

Adult Pediatric

Dermatomycoses

Clotrimazole 1% cream, solution, or lotion bid

x14-28d, apply in a thin layer to the affected

area and surrounding skin.

Topical preparations should not be used

in children < 2 years old

Vaginal preparations are not

recommended for children < 12 years

old

Lozenges should not be used in children

< 5 years old

Safety Information

Avoid applying dressings that seal the area Elevated liver function tests have been observed in patients using

Clotrimazole lozenges.

Side Effects

Local cutaneous effects may include irritation, hypersensitivity, burning, pruritus, erythema, fissuring, or swelling.

FDA Pregnancy Category COral formulation shows toxicity in animal trials. Use is not recommended during pregnancy or lactation.

Mechanism of Action / Pharmacokinetics

Clotrimazole damages the fungal cell wall and alters the permeability. It also inhibits the activity of intracellular enzymes, leading to a buildup of toxic concentrations of hydrogen peroxide within the fungal cell, causing death of the cell. Systemic absorption is minimal.

Ciclopirox

Antifungal, topical. Ciclopirox olamine is a hydroxypyridone antifungal that is

structurally unrelated to other antifungal agents.

It was first introduced in 1975 and has been accepted and used in Europe for many

years. It was approved by the FDA in 1982 for the treatment of superficial fungal

infections. A new lacquer formulation was approved in 1999.

Trade Name:

Penlac*   Dermik

Loprox*   Dermik

Dosage Forms:

Nail lacquer solution: Ciclopirox olamine 8% Penlac Nail Lacquer*

Topical Gel: Ciclopirox olamine 1% Loprox*

Cream: Ciclopirox olamine 1% Loprox*

Lotion: Ciclopirox olamine 1% Loprox*

The topical application of this drug was one of the first effective antifungals for

superficial dermatophyte, yeast, and fungal infections. The most recent formulation,

a lacquer, has made ciclopirox convenient in the treatment of nail infections.

Page 14: AntiHistamines

Used for

Tinea corporis Tinea cruris

Tinea pedis Tinea versicolor Candidiasis, cutaneous Nail lacuer- Onychomycosis

Therapeutic Regimen

Adult Pediatric

Ciclopirox 1% lotion, gel or cream applied to the affected areas twice a day.

Ciclopirox 8% nail lacquer to be applied daily as directed and removed once a week. Continue up to 48 weeks if necessary.

PediatricSafety and efficacy have not been established for children < 10 years of age.

Safety Information

Adverse Effects Cutaneous effects may include local irritation or burning when first applied.

FDA Pregnancy Category B Adequate human studies have not been completed. Animal studies have not shown adverse fetal effects. It is not known if ciclopirox is distributed in breast mi

Terbinafine Hydrochloride

Antifungal, allylamine -one of the first antifungals of the allylamine class, discovered

in 1974. It was approved for systemic use in the UK in 1991, and for topical use in the

USA in 1992.

Terbinafine is an antifungal effective against Dermatophytes, Aspergillus sp., and

Candida and Pityrosporum yeasts. Terbinafine is only fungistatic against Candida,

however cure is possible after 2-4 weeks of treatment (-).

It is available in systemic and topical formulations. Systemic treatment is usually

reserved for infections of the nails, extensive cutaneous infections or those, which have

not responded to topical therapy.

Trade Name:

Lamisil*   Novartis Lamisil DermGel*   Novartis Lamisil AT*   Novartis

Dosage Types;

Topical: Cream: Terbinafine hydrochloride 1% *Lamisil* and Lamisil AT

Solution: Terbinafine hydrochloride Lamisil

Oral: Tablets: Terbinafine hydrochloride tablets 250 mg Lamisil* Therapeutic Regimen

Page 15: AntiHistamines

Adult Pediatric

OralOnychomycosis

Lamisil 250 mg po daily x6 weeks for the fingernails, and x12 weeks for the toenails.

Tinea cruris, corporis and pedis

Lamisil 250 mg po daily x2-6 weeks

TopicalTinea corporis and cruris

Lamisil 1% 1-2x/d x1 week until significant improvement shows.

Treatment should not be continued after 4 weeks.

Tinea pedis

Lamisil 1% 2x/d x2 weeks until significant improvement shows.

Treatment should not be continued after 4 weeks.

Tinea versicolor.

Lamisil 1% 1-2x/d x2 weeks until significant improvement shows.

Treatment should not be continued after 4 weeks.

Cutaneous candidiasis

Lamisil 1% 1-2x/d x1-2 weeks until significant improvement shows.

Oral

Safety and efficacy have not been established

Topical

Safety and efficacy have not been established in children < 12 years of aged

Page 16: AntiHistamines

Treatment should not be continued after 4 weeks.

Patient Monitoring

Liver function tests are recommended before treatment and periodically during

therapy, in patients with hepatic impairment, alcoholism, and those taking

hepatotoxic drugs.

Adverse Effects

Local cutaneous effects may include mild burning, irritation, and erythema.

Cutaneous effects may include hypersensitivity reactions, including

Stevens-Johnson syndrome and toxic epidermal necrolysis.

Gastrointestinal effects may include nausea, dyspepsia, stomach pain,

reversible loss of taste and hepatitis.

Hematologic effects may include neutropenia and pancytopenia.

FDA Pregnancy Category B

Human tests have not been completed, but animal testing has not shown any adverse

fetal effects. Terbinafine is distributed in the breast milk. Treatment during

pregnancy and lactation is not recommended.

Major Drug Interactions

Concurrent use of terbinafine with caffeine, theophylline and naphtylline may

increase their toxicity; alcohol and hepatotoxic medications may increase the risk of

liver damage; drugs that induce the cytochrome P-450 system may increase the

clearance of terbinafine; drugs that inhibit the cytochrome P-450 system may

decrease the clearance of terbinafine.

Mechanism of Action / Pharmacokinetics

Terbinafine interferes with fungal ergosterol synthesis by inhibiting the enzyme

squalene epoxide in the fungal cell membrane.

This leads to fungal cell death by disruption of fungal membrane function and cell

wall synthesis. The oral dose is well absorbed from the gastrointestinal tract, and is

extensively distributed to the hair follicle, nail plate and sebum-rich skin.

It can be detected in nail clippings three weeks after the initiation of therapy.

Terbinafine undergoes first pass metabolism, involving a small percentage of the

total hepatic P450 capacity. Its elimination is primarily renal.

Topical terbinafine is minimally absorbed, less than 5% is detected systemically.

Topical terbinafine concentrates in the lipophilic stratum corneum

Page 17: AntiHistamines

Itraconazole

Itraconazole is an antifungal azole. It is a synthetic triazole analogue with a wide

spectrum of antifungal activity. It was first synthesized in 1980, and approved in

Europe in 1987.

It was approved by the FDA in 1992 for systemic mycoses, and then for

onychomycoses in 1995, and for use by pulse therapy in 1997. In 2000, itraconazole

was also approved to treat blastomycosis, histoplasmosis, and aspergellosis in

patients intolerant of amphotericin B.

Itraconazole is used effectively in the treatment of onychomycosis and candidal

infection.

It is lipophylic and quickly achieves high skin and mucous membrane

concentrations, and may still be found in the stratum corneum 4 weeks after

discontinuation of therapy.

Trade Name:

Sporanox*   Janssen

Dosage Types:

Oral: Capsules: Itraconazole 100mg Sporanox*

Solution: Itraconazole 100mg/10 mL Sporanox*

Uses

Labeled Indications Off-Label Uses

Dermatologic

Candidiasis, oropharyngeal

Dermatologic

Onychomycosis # Chromomycosis Paronychia # Leishmaniasis, cutaneous # Candidiasis, vulvo-vaginal # Candidiasis mucocutaneous # Tinea corporis # Tinea cruris# Tinea pedis# Tinea manum # Hirsutism #

# - not approved in Canada

 Therapeutic Regimen

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Adult Pediatric

Candidiasis, oropharyngeal

Itraconazole 100mg oral solution po daily x 3weeks

Onychomycosis

Itraconazole 200 mg twice a day po x1week, followed by 200 mg twice a day for the first week of each month. For toenail involvement, continue treatment x12 consecutive weeks

Safety and efficacy have not been established.

Patient Monitoring

Hepatic function tests should be monitored periodically during treatment. Serum potassium may be monitored as hypokalemia has lead to ventricular fibrillation in patients on itraconazole.

Drug Safety Information

!! Warnings & Contraindications !!

Concurrent use with cisapride, azemizole and terfenadine is contraindicated. Iatroconazole capsules not to be prescribed for onychomycosis in patients

with history of congestive heart failure. Hypokalemia has lead to ventricular fibrillation in patients on itraconazole

Adverse Effects

Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome

Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.

Other effects may include headache, dizziness and drowsiness.

FDA Pregnancy Category C Animal studies have shown itraconazole to be teratogenic and embryotoxic in dose-related studies. Iatroconazole is distributed in the breast milk.

Major Drug Interactions

Concurrent use of itraconazole anticholinergics, omeprazole, and antacids may reduce the absorption of itraconazole; with digoxin levels may be increased and should be monitored; lovstatin and simvastatin concentrations may be increased, and have been associated with rhabdomyolysis; Didanosene may decrease the absorption of itroconazole; antidiabetic agents can lead to hypoglycemia; cyclosporine and phenytoin plasma concentrations may be increased; triazolam and midazolam serum concentrations may be increased; isoniazid, rifampin metabolism may be affected; anticoagulant effects may be increased.

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Fluconazole

Fluconazole is an antifungal azole. It is a broad spectrum antifungal, first approved

in Europe in 1988 and then in America in 1990.

It was the first single dose treatment approved for vaginal candidiasis. Fluconazole is

an effective agent in the treatment and prophylaxis of Candidal infection

Trade Names:

Diflucan*   Roerig

Diflucan*   Pfizer

Dosage Types

Oral: Tablets: Fluconazole 50, 100, 150, 200mg Diflucan*

Capsules: Fluconazole 150mg Diflucan*

Suspension: Fluconazole for 10mg/mL or 40 mg/mL Diflucan

Parenteral: Fluconazole 200mg/100mL and 400mg/200mL Diflucan*

Uses:

Labeled Indications Off-Label Uses

Dermatologic

Candidiasis, vulvo-

vaginalCandidiasis,

Oropharyngeal

Dermatologic

Onychomycosis Candidiasis, cutaneous # Tinea corporis # Tinea cruris # Tinea pedis #

# - not included in Canadian labeling

 Therapeutic Regimen

Adult Pediatric

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Vulvovaginal candidiasis

Fluconazole capsules 150 mg po x1 dose

Oropharyngeal candidiasis

Fluconazole capsules 200 mg po x1,

followed by 100mg po daily x 2 weeks

Tinea pedis, cruris, corporis, versicolor (off label)

Fluconazole capsules 50 mg po daily x2-6

Dosage has not been established for infants

< 6 months old

> 6 months

Oropharyngeal candidiasis

Fluconazole oral suspension

3mg/kg x2 weeks

 

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Patient Monitoring

Hepatic function tests should be monitored periodically during treatment. Transient increases in transaminases have rarely led to hepatotoxicity in patients receiving fluconazole.

Safety Information

Dose adjustment may be required in patients with renal function impairment.

Side Effects

Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome

Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.

Hematologic effects may include agranulocytosis or thrombocytopenia.

Other effects may include headache, dizziness and drowsiness.

FDA Pregnancy Category C

Animal studies report rare fetal abnormalities. Not recommended during pregnancy or lactation.

Major Drug Interactions

Concurrent use of antidiabetic agents can lead to hypoglycemia; cyclosporine and phenytoin plasma concentrations may be increased; anticoagulant effects may be increased.

Mechanism of Action / Pharmacokinetics

Fluconazole inhibits ergosterol synthesis in the cell wall of yeast and other fungi.

In Candida albicans, fluconazole may also inhibit the transformation of blastospores into the invasive mycelial form. Fluconazole is absorbed quickly after oral administration and

is widely distributed