This slide is about Oral Griseofulvin, its pharmacology, adverse effects, dosage and administration, interactions and its role in management of dermatophytosis such as tinea corporis, tinea cruris, tinea capitis,

2. INTRODUCTION
Fungal infections
Superficial
Dermatophytosis
Non
dermatophyte
mould infections
Candidiasis
Pityriasis
versicolor
Subcutaneous Systemic Opportunistic
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytes are hyaline septate
molds
Infect keratinized tissues
Three genera, Trichophyton,
Microsporum and Epidermophyton
Classified into Tinea captis, tinea barbae,
tinea corporis, tinea cruris, tinea pedis,
tinea manuum, tinea unguium, tinea faciei

3. DERMATOPHYTOSIS
Tinea capitis
Based on
inflammation
Inflammatory
Kerion and
favus
Non
inflammatory
Grey patch,
black dot
types
Based on
spores
Ectothrix
Microsporum
Endothrix
T. tonsurans,
T. violaceum
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytic infection of scalp and hair

4. DERMATOPHYTOSIS
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Grey patch
• Circular patches
of hair loss with
broken off hairs
• M. audouinii
Black dot
• Brittle hair shaft
breaks at level of
scalp
• T. verrucosum, T.
mentagrophytes
Kerion
• Inflamed,
indurated, tender,
boggy swelling
with hair, vesicles
and pustules
• T. tonsurans, T.
violaceum, T.
soudanense
Favus
• Scutulum –
Yellow cup
shaped crust
composed of
dense mat of
mycelia and
epithelial debris
• T. schoenleinii, T.
violaceum, M.
gypseum

5. DERMATOPHYTOSIS
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytic infection of beard and mustache area
Commonest anthrophilic species – T. rubrum, Commonest zoophilic species – T. verrucosum
Inflammatory type
• Nodular and boggy like a
kerion
• Hair can be easily
epilated
Superficial or
sycosiform type
• Diffuse erythema with
perifollicular papules and
pustules resembling
bacterial folliculitis
• Commonly caused by
anthrophilic species
Circinate or
spreading type
• Identical to tinea of
glabrous skin
• Vesiculopustular lesions
at periphery and central
scaling

6. DERMATOPHYTOSIS
• Dermatophytic infection of
nonbeard regions of face
Definition
• T. mentagrophytes, T.rubrum
Etiology
• Erythematous scaly macule that
extends peripherally and
develops a raised border
• Atypical features are more
common in Tinea faciei than in
other forms of dermatophytosis
Clinical features
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.

7. DERMATOPHYTOSIS
• Dermatophyte infection of the skin
of the trunk and extremities,
excluding the hair, nails, palms,
soles and groin
Definition
• T. rubrum, T. mentagrophytes, M.
canis
Etiology
• Typical lesion is annular or polycylic
• Borders are erythematous and
vesicular or scaly, but center is
clear
Clinical features
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.

8. DERMATOPHYTOSIS
Introduction
• Variant of Tinea corporis
• Also known as Tokelau
Etiology
• T. concentricum
Clinical features
• Begin as squamous annular
concentric plaques, some with
erythema
• With time, they become lamellar as
they have abundant thick scales that
adhere to one side, giving
appearance of tiles, fish scales or
lace
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.

9. DERMATOPHYTOSIS
Definition
• Dermatophytic infection of groin
Etiology
• T. rubrum, T. mentagrophytes, E.
floccosum
Clinical features
• Well marginated raised border,
composed of multiple
erythematous papulovesicles
and a clear center
• Usually bilateral but
asymmetrical
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.

10. DERMATOPHYTOSIS
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytic infection of feet
Commonly caused by T. rubrum, T. mentagrophytes, E. floccosum
Chronic
intertriginous
•Fissuring, scaling or
maceration in
interdigital area
•May spread to sole but
seldom involve dorsum
Chronic
papulosquamous
•Inflammation and a
patchy or diffuse
moccasin like scaling
over soles
Vesicular or
vesiculobullous
•Small vesicles or
vesiculopustules
•Seen near instep and
on mid-anterior plantar
surface
Acute ulcerative
variant
•Maceration, weeping,
denudation and
ulceration
•Obvious white
hyperkeratosis and
pungent odor if
complicated by
bacterial infection

11. DERMATOPHYTOSIS
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytic infection of palmar skin
Commonly caused by T. rubrum and E. floccosum
Non inflammatory squamous
• Diffuse Hyperkeratosis of palms and
fingers
• Accentuation of flexural creases
Inflammatory/vesicular/dyshidrotic
• Clusters of multiloculated vesicles
• Annular or segmental pattern

12. DERMATOPHYTOSIS
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.
Dermatophytic infection of nail plate
Commonly caused by T. rubrum, T. mentagrophytes var intedigitale and E. floccosum
Distal and lateral subungual onychomycosis
• Most common type, T. rubrum
• Starts by invasion of stratum corneum of hyponychium of distal nail bed or lateral nail fold
Proximal subungual onychomycosis
• Early indicator of HIV infection, T. rubrum, T. mentagrophytes, T. tonsurans
• Initially whitish or brownish area on proximal part of nail plate, later involves entire nail
White Superficial onychomycosis
• T. mentagrophytes, T. rubrum
• Well circumscribed powdery white patches away from free edge of nail
Endonyx
• T. soudanense, T. violaceum
• Milky white discoloration of nail plate without surface change
Total dystrophic onychomycosis
• In above clinical variants, as infective process continues, invasion of nai plate results in gross
and total destruction of nail

13. DERMATOPHYTOSIS
Clinical
Wood’s lamp
Potassium hydroxide
mount
Fungal Culture
Antifungal
susceptibility testing

14. Griseofulvin acts by inhibiting
fungal cell replication

15. GRISEOFULVIN
Robertson DB, Maibach HI. Dermatologic Pharmacology. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical
Pharmacology. New York: The McGraw-Hills Companies Inc. 1066-7.
• Spiro-benzo[b]furan
• Insoluble in water
• Fungistatic drug
STRUCTURE

16. GRISEOFULVIN
1939
• Isolated from the mold Penicillium
griseofulvum Dierckx by Oxford
1958
• Started using from treatment of dermatophytic
infections (First significant oral agent)
Now
• Use is largely superseded by Terbinafine and
Itraconaze except for Tinea capitis
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.

17. GRISEOFULVIN
Absorption
• Poor
• Enhanced by fatty food and smaller particle size
Peak plasma levels
• 2 to 4 hours
Half life
• 9.5 to 22 hours
Protein binding
• 84%
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.

18. GRISEOFULVIN
Metabolism
• Hepatic
• Major metabolites: 6-demethyl-griseofulvin
and its glucuronide conjugate
Excretion
• Renal 50%
• 36% in feces
• 1% Excreted unchanged in urine
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.

19. GRISEOFULVIN
Micronizing
Ultramicronizing
Solubilizing
• Small particle size
• Standard preparation
• Smallest particle size
• Half the dose of
micronized is enough
• Polyethylene glycol
• Enhances absorption
further
Robertson DB, Maibach HI. Dermatologic Pharmacology. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical
Pharmacology. New York: The McGraw-Hills Companies Inc. 1066-7.

20. GRISEOFULVIN
Fungistatic action
Thus inhibiting fungal cell division
Causes arrest of mitosis (at metaphase
stage)
Binds to tubulin and prevents formation of
microtubules
Enters the fungal cell (Intracellular action)
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

21. GRISEOFULVIN
Robertson DB, Maibach HI. Dermatologic Pharmacology. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical
Pharmacology. New York: The McGraw-Hills Companies Inc. 1066-7.
Binds to keratin & protects skin from
new infection
Binding is not firm unlike itraconazole
Inhibits nucleic acid synthesis
Narrow spectrum of antimycotic
activity

22. GRISEOFULVIN
Tinea capitis*
Tinea unguium
Tinea corporis*
Tinea cruris*
Tinea pedis*
Tinea barbae*
Tinea
imbricata
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.
*Not justified for minor or trivial infections which
will respond to topical agents alone

23. GRISEOFULVIN
Trichophyton
• T.mentagrophytes
• T.interdigitalis
• T.verrucosum
• T.megnini
• T.gallinae
• T.crateriform
• T.sulphureum
• T.schoenleini
Microsporum
• M.audouini
• M.canis
• M.gypseum
Epidermophyton
• E.floccosum
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf

24. GRISEOFULVIN
Candidiasis
Pityriasis versicolor
Deep fungal infections
Bacterial infections
Actinomycosis
Nocardiosis
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

25. GRISEOFULVIN
Availability
• 250 mg tablets
• 500 mg tablets
Dose
• 10 to 20
mg/kg/day
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

26. INDICATIONS
SOURCE DOSE DURATION COMMENT
Rooks 10 mg/kg OD 6 weeks Used particularly for
Microsporum infections (Superior
efficacy than terbinafine)
20 mg/kg is considered in some
T. tonsurans and T. schoenleinii
Fitzpatrick 20-25 mg/kg OD 6-8 weeks
IADVL 5-25 mg/kg OD 8 week Griseofulvin continues to be the
treatment of choice for tinea
capitis where causative agent is
undetected
Continue for 2 weeks beyond
cure

27. GRISEOFULVIN IN TINEA CAPITIS
J Am Acad
Dermatol
2011;64:663-70
• Tinea capitis caused by
Trichophyton species:
Terbinafine > Griseofulvin
• Tinea capitis caused by
Microsporum species:
Griseofulvin > Terbinafine
Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the
treatment of tinea capitis. J Am Acad Dermatol. 2011;64:663–70

28. GRISEOFULVIN vs OTHERS
Cochrane library: Systemic antifungal therapy for tinea capitis in children (Review) 2016

29. GRISEOFULVIN vs TERBINAFINE FOR TINEA CAPITIS
Griseofulvin
• Effective for
Microsporum
• Approved for more
than 2 years
Terbinafine
• Effective for
Trichophyton
• Approved for more
than 4 years
Cochrane library: Systemic antifungal therapy for tinea capitis in children (Review) 2016

30. GRISEOFULVIN vs TERBINAFINE FOR TINEA CAPITIS
Treats ectothrix infections
(Microsporum) more effectively
Reach outside hair shaft (ecto)
Griseofulvin and azoles are
secreted in sweat
Treats endothrix infection (Trichophyton)
more effectively
But it incorporates into hair shaft
Terbinafine cannot reach ectothrix infection
Children have little sebum secretion prior to
puberty
Terbinafine is secreted in sebum
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.

31. GRISEOFULVIN vs AZOLES FOR TINEA CAPITIS
Cochrane library: Systemic antifungal therapy for tinea capitis in children (Review) 2016
• No evidence that griseofulvin was superior in
efficacy
• Limitation: Small trials
Azoles
• FDA approval only for children more than 12 years
of ageItraconazole
• Recommended as an alternative to terbinafine
• Optimal regimen unclearFluconazole
• Not recommended in children because of severe
hepatotoxicityKetoconazole

32. INDICATIONS
SOURCE DOSE FINGERNAIL
DURATION
TOENAIL
DURATION
Rooks 1 g OD 4 months 8 months
Fitzpatrick 0.75 to 1 g OD 4 months 6 months
IADVL 500 mg OD 6 months 12 months

33. INDICATIONS
SOURCE DOSE DURATION COMMENT
Rooks 1 g OD 4 weeks Second line treatment for
widespread disease
Much longer treatment required for
extensive disease
Fitzpatrick 500 mg OD 2-4 weeks
IADVL 500 mg OD 4-8 weeks

34. INDICATIONS
SOURCE DOSE DURATION
Rooks - -
Fitzpatrick 500 mg OD 2-4 weeks
IADVL 500 mg OD 2-4 weeks

35. INDICATIONS
SOURCE DOSE DURATION
Rooks - -
Fitzpatrick 1 g OD 6 weeks
IADVL 0.5 to 1 g OD 2-4 weeks

36. INDICATIONS
SOURCE DOSE DURATION COMMENT
Rooks - - -
Fitzpatrick - - -
IADVL 500 mg BD 4-8 weeks Higher doses for relapse
Chronic moccasin type due to T.
rubrum – 2 to 3 months
Not recommended when infection
is limited to toe cleft

37. INDICATIONS (OFF LABEL)
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.
SOURCE DOSE DURATION COMMENT
Wolverton 500 mg BD 4-6 weeks Requires concomitant topical
therapy

38. GRISEOFULVIN
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.
Hepatic impairment
Porphyria
Hypersensitivity to drug
Pregnancy
Lupus Erythematosus

39. SPECIAL POPULATION
Reports
• Several reports of conjoined
twins
Mechanism
• Interferes with chromosomal
distribution during cell division
Contraception
• Women need additional
contraception during and 1
month after use, men should
wait 6 months before fathering
child
Gupta AK. Systemic Antifungal Agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Amsterdam:
Elsevier Inc.; 2013. 98-120.
• Risk cannot be ruled out
– human studies are
lacking
• Animal studies may or
may not show risk
• Potential benefits may
justify potential risk
CATEGORY

40. SPECIAL POPULATION
>2 years
• FDA approved
• Acceptable first
line treatment
<2 years
• Limited data
• In practice,
used frequently
with few side
effects and
high efficacy
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

41. SPECIAL POPULATION
Safety has not been
formally evaluated in
trials
However, studies
including elderly
population did not
show increased
incidence of
adverse effects in
elderly
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

42. GRISEOFULVIN
Gastrointestinal effects
• Most common
• Nausea, vomiting and
dyspepsia
CNS effects
• Most common
• Headache, dizziness, insomnia
Hematological toxicity
• Leukopenia
Hepatotoxicity
Cutaneous effects
• Photosensitivity and
Photolichenoid eruptions
• Precipitate lupus
erythematosus
• Precipitation of acute
intermittent porphyria
• Erythema multiforme
• Steven-Johnson
syndrome
• Urticaria and Angioedema
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

43. GRISEOFULVIN
• Griseofulvin decreases anticoagulant property of
warfarin
• By CYP3A4 induction
Warfarin
• Griseofulvin decreases effectiveness of OCP
• By CYP3A4 induction
Oral Contraceptive
Pills
• Phenobarbitone reduces blood levels of
GriseofulvinPhenobarbitone
• Disulfiram like reaction
• Severe nausea and vomitingAlcohol
Shenoy MM, Shenoy MS. Superficial Fungal Infections. In: Sacchidanand S, Oberai C, Inamadar AC, editors. IADVL Textbook
of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. 459-516.

44. GRISEOFULVIN
• KOH
• Fungal Culture
• Histology
Documentation of positive
tests
No specific baseline
investigations
Jacob R, Konnikov N. Oral Antifungal Agents. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors.
Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: The McGraw-Hill Companies Inc.; 2012. 2804-5.

45. GRISEOFULVIN
Prolonged
Therapy
> 8 weeks
CBC
LFTRFT
Robertson DB, Maibach HI. Dermatologic Pharmacology. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical
Pharmacology. New York: The McGraw-Hills Companies Inc. 1066-7.

46. CONCLUSION
For
• First line therapy for
tinea capitis caused
by Microsporum
species
• Second line therapy
for Tinea corporis
Against
• Limited spectrum of
coverage
• Lengthy courses