Pharmacokinetics in children

Premature age	Cmax (µg/ml)	Tmax (hours)	T½ (hours)	Cl (ml/min/kg)	Vd (l/kg)
1 day	5.5	2.2	88.6	0.18	1.18
7 days	12.8	1.6	67.5	0.33	1.84
13 days	10.0	1.6	55.2	0.52	2.25

T½ = 15-20 hours in children (> 3 months) and the VP is on average 0.95 l/kg (3 months to 12 years) and 0.70 l/kg (12 to 16 years) [Brammer 1994, Saxén 1993]. Children on ECMO: Vd = 1.5 l/kg, Cl = 0.28 ml/min/kg, t½ = 60 hours [Watt 2012]

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Mucosal candidiasis

Oral Neonaten 0 days up to 14 days Initial dose: Once on day 1 6 - 12 mg/kg/day in 1 dose Maintenance dose: (=half of the starting dose) 3 - 6 mg/kg per 72 hours in 1 dose Duration of treatment: The duration of treatment is based on the clinical and mycological response.   Neonates 14 days up to 28 days Initial dose: Once only on Day 1: 6 - 12 mg/kg/day in 1 dose    . Maintenance dose: (= half the initial dose) 3 - 6 mg/kg per 48 hours in 1 dose Duration of treatment: The duration of treatment is based on the clinical and mycological response. 1 month up to 12 years Initial dose: Once only on Day 1: 6 - 12 mg/kg/day in 1 dose. Max: 800 mg/day. Maintenance dose: (= half the initial dose) 3 - 6 mg/kg/day in 1 dose. Max: 400 mg/day. Duration of treatment: The duration of treatment is based on the clinical and mycological response. 12 years up to 18 years Initial dose: 400 mg/day in 1 dose Maintenance dose: 200 - 400 mg/day in 1 dose Raise the maintenance dose to 400 mg/day, depending on the clinical response.  . Duration of treatment: The duration of treatment is based on the clinical and mycological response. Only in exceptional and very severe infections: up to 20 mg/kg/day in a single dose, maximum 1600 mg/day.   Intravenous Neonates 0 days up to 14 days Initial dose: Once only on Day 1: 6 - 12 mg/kg/day in 1 dose Maintenance dose: (= half the initial dose) 3 - 6 mg/kg per 72 hours in 1 dose Duration of treatment: The duration of treatment is based on the clinical and mycological response. Neonates 14 days up to 28 days Initial dose: Once only on Day 1: 6 - 12 mg/kg/day in 1 dose Maintenance dose: (= half the initial dose) 3 - 6 mg/kg per 48 hours in 1 dose Duration of treatment: The duration of treatment is based on the clinical and mycological response. 1 month up to 12 years Initial dose: Once only on Day 1: 6 - 12 mg/kg/day in 1 dose. Max: 800 mg/day. Maintenance dose: (= half the initial dose) 3 - 6 mg/kg/day in 1 dose. Max: 400 mg/day. Duration of treatment: The duration of treatment is based on the clinical and mycological response. 12 years up to 18 years Initial dose: 400 mg/day in 1 dose Maintenance dose: 200 - 400 mg/day in 1 dose Raise the maintenance dose to 400 mg/day, depending on the clinical response.. Duration of treatment: The duration of treatment is based on the clinical and mycological response. Only in exceptional and very severe infections: up to 20 mg/kg/day in a single dose, maximum 1600 mg/day.

Systemic deep candidiasis, cryptococcal infections

Oral Neonates Gestational age < 30 weeks [22] [39] [41] [42] [43] [44] Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose Premature neonates Gestational age ≥ 30 weeks [22] [39] [41] [42] [43] [44] Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose In case of severe infection, the dose can be increased up to 20 mg/kg/day Term neonate [22] [39] [41] [42] [43] [44] Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose In case of severe infection, the dose can be increased up to 20 mg/kg/day 1 month up to 12 years Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose. Max: 800 mg/day. Maintenance dose: 12 mg/kg/day in 1 dose. Max: 400 mg/day. Duration of treatment: The length of treatment is based on the clinical and mycological response. 12 years up to 18 years Initial dose: 800 mg/day in 1 dose Maintenance dose: 400 mg/day in 1 dose Lower the maintenance dose to 200 mg/day, depending on the clinical response.. Duration of treatment: The length of treatment is based on the clinical and mycological response. Only in exceptional and very severe infections: up to 20 mg/kg/day in a single dose, maximum 1600 mg/day. Intravenous Premature neonates Gestational age < 30 weeks [22] [39] [41] [42] [43] [44] Initial dose: Once only on day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose Premature neonates Gestational age ≥ 30 weeks [22] [39] [41] [42] [43] [44] Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose In case of severe infection, the dose can be increased up to 20 mg/kg/day. Term neonate [22] [39] [41] [42] [43] [44] Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose Maintenance dose: 12 mg/kg/day in 1 dose In case of severe infection, the dose can be increased up to 20 mg/kg/day. 1 month up to 12 years Initial dose: Once only on Day 1: 25 mg/kg/day in 1 dose. Max: 800 mg/day. Maintenance dose: 12 mg/kg/day in 1 dose. Max: 400 mg/day. Duration of treatment: The length of treatment is based on the clinical and mycological response. 12 years up to 18 years Initial dose: 800 mg/day in 1 dose Maintenance dose: 400 mg/day in 1 dose Lower the maintenance dose to 200 mg/day, depending on the clinical response.. Duration of treatment: The length of treatment is based on the clinical and mycological response. Only in exceptional and very severe infections: up to 20 mg/kg/day in a single dose, maximum 1600 mg/day.

Prophylaxis for candidiasis, prophylaxis for cryptococcal infections

Oral VLBW premature neonates Gestational age < 37 weeks and < 1000 g [8] [11] [13] [14] [15] [16] [22] [25] [40] [45] [47] 6 mg/kg/dose every 3 days. Duration of treatment: Prophylaxis is indicated as long as an intravenous administration route is present. Full-term neonates 0 days up to 14 days 6 mg/kg per 72 hours in 1 dose Full-term neonates 14 days up to 28 days 6 mg/kg per 48 hours in 1 dose 1 month up to 12 years 3 - 6 mg/kg/day in 1 dose. Max: 200 mg/day. 12 years up to 18 years 200 - 400 mg/day in 1 dose Intravenous VLBW premature neonates Gestational age < 37 weeks and < 1000 g [8] [11] [13] [14] [15] [16] [22] [25] [40] [45] [47] 6 mg/kg/dose every 3 days. Duration of treatment: Prophylaxis is indicated as long as an intravenous administration route is present. Full-term neonates 0 days up to 14 days 6 mg/kg per 72 hours in 1 dose Full-term neonates 14 days up to 28 days 6 mg/kg per 48 hours in 1 dose 1 month up to 12 years 3 - 6 mg/kg/day in 1 dose. Max: 200 mg/day. 12 years up to 18 years 200 - 400 mg/day in 1 dose

Prophylaxis for candidiasis in children on ECMO
Intravenous Term neonate [23] [24] Initial dose: Once only on Day 1: 12 mg/kg/day in 1 dose Maintenance dose: 6 mg/kg/day in 1 dose 1 month up to 18 years [23] [24] Initial dose: Once only on Day 1: 12 mg/kg/day in 1 dose Maintenance dose: 6 mg/kg/day in 1 dose This dosage recommendation should be applied with caution in children aged > 2 years; very little research has been done for this as yet.

Vaginal candidiasis
Oral 12 years up to 18 years [10] 150 mg/dose, once only. In the event of recurrences (> 4 episodes per year): 150 mg/week in a single dose for 6 months

Tinea capitis
Oral Term neonate [26] 6 mg/kg/day in 1 dose Duration of treatment: 4-8 weeks 1 month up to 18 years [26] 6 mg/kg/day in 1 dose Duration of treatment: 4-8 weeks

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2

Adjustment not necessary

GFR 30-50 ml/min/1.73 m2

Day 1: 100% of regular dose. Day 2 and further: 50 % of regular dose. Interval between two doses does not require adjustment
Dosage adjustment is not necessary in case of vaginal candidiasis (single administration or administration of 150 mg once a week).

GFR 10-30 ml/min/1.73 m2

5 percentage of single dose and dosing interval : uur Day 1: 100% of regular dose. Day 2 and further: 50 % of regular dose. Interval between two doses does not require adjustment
Dosage adjustment is not necessary in case of vaginal candidiasis (single administration or administration of 150 mg once a week).

GFR < 10 ml/min/1.73 m2

Day 1: 100% of regular dose. Day 2 and further: 50 % of regular dose. Interval between two doses does not require adjustment.
Dosage adjustment is not necessary in case of vaginal candidiasis (single administration or administration of 150 mg once a week).

Patients on dialysis

Give 100% of the recommended dose after every haemodialysis. On days that dialysis is not being done, a lower dose should be given based on the GFR (see above).

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Impaired hepatic function occurs more frequently in children. Hypersensitivity and anaemia are specific side effects that occur in children.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions

No information available on specific warnings and precautions in children.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Antibiotics
	Amphotericin B (parenteral, inhalation) Related Medicines Menu">	J02AA01

Triazole and tetrazole derivatives
	Itraconazole Related Medicines Menu">	J02AC02
	Voriconazole Related Medicines Menu">	J02AC03

Other antimycotics for systemic use
	Anidulafungine Related Medicines Menu">	J02AX06
	Caspofungin Related Medicines Menu">	J02AX04
	Flucytosine Related Medicines Menu">	J02AX01
	Micafungin Related Medicines Menu">	J02AX05

References

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4. Martínez Sesmero JM, et al, Fungal chemoprophylaxis with fluconazole in preterm infants, Pharm World Sci, 2005, 27, 475-7
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31. PFIZER PHARMA PFE, SmPC Diflucan Derm 50 mg Hartkapseln (28858.00.00), 11/2017
32. PFIZER PHARMA PFE, SmPC Diflucan® 40 mg/ml Pulver zur Herstellung einer Suspension zum Einnehmen (89459.00.00), 06/2017
33. EurimPharm Arzneimittel, SmPC Diflucan Trockensaft 10 mg/ml (52339.00.00), 03/2017
34. PFIZER PHARMA PFE, SmPC Fungata 150mg HKps (15824.00.00), 11/2017
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36. Aristo Pharma, SmPC Fluconazol Aristo ® 50 mg/100 mg/150 mg/200 mg Kapseln (52713.00.00 / 52713.01.00 / 52713.02.00 / 52713.03.00 ), 03/2017
37. Accord Healthcare Limited, SmPC Fluconazol Accord 50 mg | 100 mg | 150 mg | 200 mg Hartkapseln (84490.00.00 / 84491.00.00 / 84492.00.00 / 84493.00.00), 12/2017
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