Antifungals

Question 1

Griseofulvin

1. Class
2. Indications
3. Dose range/ best time for admin/ frequency
4. Monitoring
5. Counselling

Answer 1

1. antifungal agent
2. Dermatophyte infection of skin (tinea corporis), scalp and hair (tinea capitis), nails (tinea unguium), feet (tinea pedis) and groin (tinea cruris) where topical treatment has failed or is inappropriate
   TX of choice for tinea capitis
3. Duration of treatment depends on thickness of keratin layer: skin and hair, 4–6 weeks; nails, up to 12 months.
   Tinea of skin, hair, groin - Oral, 500mg once D.
   Tinea of feet, nails - Oral, 1g once D.
   Child >2 years - Oral, 10-20mg/kg (max 1g) once D.
4. Lupus erythematosus—C/I.
   Men - May affect sperm; manufacturer advises men not to father a child during, and for 6 months after, tx despite no reports of adverse effects on the fetus.
   Hepatic - C/I in severe hepatic disease.
   Women - use additional non-hormonal contraception while taking and for 1 month after stopping griseofulvin.
   Pregnancy - Limited info, avoid use
   Breastfeeding - No data; avoid breastfeeding.
5. Take with food/milk to increase absorption.
   LABEL 8, 16
   Very occasionally effects such as increased HR and skin flushing may occur if you take alcohol during your griseofulvin course.
   Contraceptive pill will not be as effective while you are taking griseofulvin; you should use additional contraception, eg condoms, during treatment and for 4 weeks afterwards.
   Nail infections - This treatment needs to be taken until the infected nail has grown out.

Spectrum of activity is narrow and largely confined to dermatophytes, so an accurate diagnosis is desirable before starting a long course of treatment
monitor complete blood count during prolonged treatment

Question 2

Fluconazole (Diflucan One, Dizole One) cap, 150 mg

Miconazole oral gel, 20 mg/g, 15 g, 40 g, Daktarin
oral gel, 20 mg/g, 40 g, Decozol

Answer 2

1. Azoles
2. Vulvovaginal candidiasis where topical therapy has failed
   Candidiasis, oropharyngeal or oesophageal
3. 50-400mg daily.
   Vulvovaginal candidiasis: 150 mg as a single dose.
   Use the same dose for oral and IV administration.
4. Prolonged or high-dose treatment: monitor LIVE FN and serum K+.
   Renal fn- dose reduce
   MODERATE CYP3A4/5 INHIBITOR
   Prolong the QT interval
   MICON- Warfarin: possible increased anticoagulant effect (especially after use of the oral gel). Monitor INR.
5. LABELs: Capsule (multi-dose): 5, 21, A, D; capsule (single-dose): 5, 21, A; oral suspension: 5, 7a (14 days), 21, D, J

This medicine can cause nausea, diarrhoea, headaches and rash.
Tell dr if you develop yellowing of the eyes or skin, unusual tiredness, loss of appetite or a severe rash.
This does not apply to patients taking miconazole.
This medicine interacts with many drugs; tell your doctor and pharmacist that you are taking this medicine before starting or stopping any medicines, including herbal and over-the-counter products.

MICONAZOLE
LABELs: Cream/ointment/powder/shampoo/solution/tincture: E, J, K; oral gel: 5, D
A/Es= mild GI disturbances
Oral gel: Place the measured dose of gel on the tongue and hold in the mouth for as long as possible (30–60 seconds) before swallowing. Avoid eating or drinking for 1 hour after applying the gel.
If using in an infant or young child, place small amounts at the front of the mouth, or smear gel onto the affected areas, to avoid choking.
Dentures: apply gel to dentures after cleaning and leave overnight.Continue using the gel for several days after symptoms disappear.
Side effects:
Topical: this medicine can occasionally cause localised stinging or itching

Question 3

Itraconazole
cap, 50 mg, 15, 60, Lozanoc, PBS‑A[60]1
cap, 100 mg, 15, 28, 60, Sporanox, PBS‑A[60]1
cap, 100 mg, 60, Itracap, Itranoxa, PBS‑A1
oral liquid, 10 mg/mL, 150 mL, Sporanox

Posaconazole
tab, 100 mg (controlled release), 24, Noxafil, PBS‑A1

Ketoconazole

Voriconazole
tab, 50 mg, 56, Vfend, Vttack, Vzolea, PBS‑A1
tab, 200 mg, 56, Vfend, Vttack, Vzolea, PBS‑A1

Answer 3

1. Azoles
2. Vulvovaginal candidiasis where topical therapy has failed
   Candidiasis, oropharyngeal or oesophageal
3. 50–400 mg daily.
   POSA= 100-400mg once-TDS.
   VORI= 400mg 12-hourly for two doses, then 200mg 12-hourly.
4. Prolonged or high-dose treatment: monitor LIVE FN and serum K+.
   Renal fn- dose reduce
   STRONG CYP3A4/5 INHIBITOR
   Prolong the QT interval
   Negative inotropic drugs, eg calcium channel blockers—itraconazole has a negative inotropic action and may add to their effect.
   May precipitate or worsen existing HF
   ↓ gastric acidity/tx PPI—impairs absorption give w/COLA drink and monitor clinical response.
   Children and immunocompromised patients: TDM to assess dose requirements.
   Check 5–7 days after starting treatment or after changing dose.
5. LABELs: Capsule: 4b*, 5, B, D; oral solution: 3b, 5, D
   Sporanox caps/bioequivalents: take with FOOD (but not a rice meal) for best absorption.
   Oral liquid: take on an empty stomach, at least 1 hour before food.

This medicine can cause dizziness, headaches, nausea, indigestion, itch, and diarrhoea or constipation.
If you develop yellowing of the eyes or skin, unusual tiredness or loss of appetite, tell your doctor.

POSA= Oral liquid: take with or after a high-fat meal.
Tablet: swallow whole with food; do not crush or chew.

VORI= LABELs: Oral suspension: 3b, 5, 7a (14 days), 8, 12, 21, D, J; tablet: 3b, 5, 8, 12, 21, A, D
This medicine can cause fever, rash, nausea, vomiting, diarrhoea, abdominal pain and headaches.
You may experience some temporary changes to your vision (e.g. blurred vision, sensitivity to light). Consult your doctor if they become troublesome. Do not drive (especially at night) or operate machinery if you are affected.
If you develop a severe rash or bone pain, tell your doctor immediately.

VISION (e.g. altered/enhanced visual perception, blurred vision, colour changes, photophobia)
Prolong QT interval
LONGTERM MONITOR skin cancers

Question 4

Amphotericin B
lozenge, 10 mg, 20, Fungilin, PBS
Liposomal amphotericin B
inj, 50 mg (powder), 10, AmBisome
↑↓△

Answer 4

1. Polyene
2. Severe systemic fungal infections
   Treatment oral and perioral candidiasis (lozenge)
3. Oral candidiasis: one lozenge (10 mg) QID for 1-2 weeks.
   systemic= IV 3-5mg/kg OD; use the higher end of the dose range for CNS disease and fusariosis.
4. IV infusion: monitor renal and hepatic function, electrolytes and complete blood count.
   Pregnancy/breastf= safe to use orally as absorption from the GIT is minimal. Minimal systemic absorption following oral administration.
5. LABEL: D
   It is best to use the lozenge after (rather than before) a meal or drink. Continue to use them for several days after your symptoms disappear.
   Side effects:
   Lozenges: this medicine can cause mild nausea, vomiting and diarrhoea, and black discolouration of faeces.
   Remove dentures before sucking lozenge

Infusion reactions= fever, chills, hypotension, anorexia, nausea, vomiting, headache, malaise, muscle and joint pain; usually lessen with continued treatment.

Question 5

Nystatin
tab, 500 000 units, 50, Nilstat Oral, PBS
cap, 500 000 units, 50, Nilstat Oral, PBS
oral liquid, 100 000 units/mL, 24 mL, 1, Mycostatin Oral Drops
oral liquid, 100 000 units/mL, 24 mL, 1, Nilstat Oral Drops
cream, 100 000 units/g, 15 g, Mycostatin
vaginal cream, 100 000 units/dose, 75 g, Nilstat

Answer 5

1. Polyene
2. Oropharyngeal candidiasis
   Tx of intestinal candidiasis
3. Adult/child= oral liquid 100,000units (1mL) QID for 7-14 days.
   Intestinal candidiasis
   Adult/child= tablet/capsule 500 000–1 million units TDS-QID.

TOPICAL= Adult/child= apply liberally to affected areas 2–4 times a day until infection resolved (at least 14 days).

VAGINAL= Insert 1 applicatorful (100 000 units) into the vagina daily at bedtime for 14 days.

4. Pregnancy/breastf= safe
   nystatin oral liquid is effective treatment for minor oral fungal infections
   treatment with oral itraconazole or fluconazole is often required in immunocompromised people (especially with HIV)

5. LABELs: Caps/tab: D; oral liquid: D, J; 
Oral= can occasionally cause nausea, vomiting and diarrhoea (more severe w/doses >5 million units daily).
Shake the bottle. Using the measuring syringe provided, place 1 mL of suspension into the mouth. Swirl the liquid around in the mouth for as long as possible (30–60 seconds) before swallowing.
For an infant, place half of the dose in each cheek.
Try to avoid drinking or eating for 1 hour after a dose.
Continue tx for as long as directed, or for 2 days after your symptoms disappear.
Oral drops (patients who wear dentures): remove dentures at night, and clean and soak as directed. Apply several drops of nystatin to the fitting surface of the dentures before re-inserting them into the mouth in the morning.

TOPICAL= LABELs=cream: E= For this treatment to be successful you have to use it regularly.
Continue using the treatment for 2 weeks after symptoms have gone.
S/Es= localised irritation, itching and a rash.

VAGINAL= LABELs=vaginal cream: D, L
Vaginal cream: your symptoms should start to improve within 1–3 days and should disappear within 1–3 weeks.
Topical cream: your symptoms should start to improve within 1–3 days.
Vaginal cream: can damage condoms and diaphragms; these contraceptive methods should not be used while using the cream.
Even on prolonged administration nystatin is virtually nontoxic, non-sensitising and well tolerated by all age groups.

Question 6

Terbinafine

tab, 250 mg (scored), 42, Lamisil, Tamsil, Tinasila, PBS‑A1/RPBS‑A1

https://amhonline-amh-net-au.ezproxy.lib.monash.edu.au/chapters/dermatological-drugs/drugs-skin-infections/other-antifungals-skin/terbinafine-skin

Answer 6

1. antifungal
2. Onychomycosis (tinea unguium)
   Dermatophyte infection of skin, groin, feet, when topical treatment is ineffective or inappropriate
3. 250mg OD (6 weeks for fingernails; 12 weeks (sometimes longer) for toenails).
4. Psoriasis, lupus erythematosus—may be exacerbated or precipitated by terbinafine.
   Renal fn= reduce dose
   LFTs at baseline; monitor these and blood count if treating for >6 weeks
   Stop tx if hepatotoxicity occurs or a rash worsens.
   Fewer drug interacts than azoles.
5. LABELs: Cream/gel/solution: K; tablet: 5, 8, 13, D
   Nausea, diarrhoea, dyspepsia, decreased appetite, abdominal cramps, headaches and rash.

Tell dr if you feel unusually tired, nauseous or are not eating; or if you notice dark urine, pale faeces or yellowing of the whites of your eyes or skin; or if you develop signs of an infection (e.g. fever, sore throat, mouth ulcers) or unusual bruising.

Nail infection: tx should cure your nail infection but the nail needs to grow out before it looks completely healthy. May take months.