DAKTARIN™ Oral Gel

Each gram of Daktarin Oral Gel contains 20 mg of miconazole.

For excipients, see 6.1.

Oral gel.

White gel with orange taste.

Oral treatment and prevention of fungal infections of the oropharynx and gastrointestinal tract, and of super infections due to Gram-positive bacteria.

For oral administration.

Dosage is based on 15 mg/kg/day (0.625 ml/kg/day).

Adults:

1-2 spoonfuls (5-10 ml) of gel four times per day.

Elderly:

As for adults.

Children aged 6 years and over:

One spoonful (5 ml) of gel four times per day.

Children aged 2-6 years:

One spoonful (5 ml) of gel twice per day.

Infants 4 months- 2 years:

Half a spoonful (2.5 ml) of gel twice per day. Each dose should be divided into smaller portions (see section 4.4)

The lower age limit should be increased by 1-2 months for infants who are pre-term, or infants exhibiting slow neuromuscular development.

For localised lesions of the mouth, a small amount of gel may be applied directly to the affected area with a clean finger.

For topical treatment of the oropharynx, the gel should be kept in the mouth for as long as possible.

Treatment should be continued for up to 2 days after the symptoms have cleared.

For oral candidosis, dental prostheses should be removed at night and brushed with the gel.

Known hypersensitivity to miconazole or to any of the excipients.

In infants less than 4 months of age or in those whose swallowing reflex is not yet sufficiently developed.

In patients with liver dysfunction.

Coadministration of the following drugs that are subject to metabolism by CYP3A4: (See Section 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction)

- Substrates known to prolong the QT-interval e.g., astemizole, cisapride, dofetilide, mizolastine, pimozide, quinidine, sertindole and terfenadine

- Ergot alkaloids

- HMG-CoA reductase inhibitors such as simvastatin and lovastatin

- Triazolam and oral midazolam

If the concomitant use of Daktarin and anticoagulants is envisaged, the anti-coagulant effect should be carefully monitored and titrated. (see section 4.5)

It is advisable to monitor miconazole and phenytoin levels, if these two drugs are used concomitantly.

In patients using certain oral hypoglycaemics such as sulphonylureas, an enhanced therapeutic effect leading to hypoglycaemia may occur during concomitant treatment with miconazole and appropriate measures should be considered (See Section 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction).

Particularly in infants and young children, caution is required to ensure that the gel does not obstruct the throat. Hence, the gel should not be applied to the back of the throat and each dose should be divided into smaller portions. Observe the patient for possible choking.

The lower age limit should be increased by 1-2 months for infants who are pre-term, or infants exhibiting slow neuromuscular development.

When using any concomitant medication the corresponding label should be consulted for information on the route of metabolism. Miconazole can inhibit the metabolism of drugs metabolised by the CYP3A4 and CYP2C9 enzyme systems. This can result in an increase and/or prolongation of their effects, including adverse effects.:

Oral miconazole is contraindicated with the coadministration of the following drugs that are subject to metabolism by CYP3A4 (See Section 4.3 Contraindications);

- Substrates known to prolong the QT-interval e.g., astemizole, cisapride, dofetilide, mizolastine, pimozide, quinidine, sertindole and terfenadine

- Ergot alkaloids

- HMG-CoA reductase inhibitors such as simvastatin and lovastatin

- Triazolam and oral midazolam

When coadministered with oral miconazole the following drugs should be used with caution because of a possible increase or prolongation of the therapeutic outcome and/or adverse events. If necessary, their dosage should be reduced and, where appropriate, plasma levels monitored:

Drugs subject to metabolism by CYP2C9 (see Section 4.4 Special Warnings and Precautions for Use);

- Oral anticoagulants such as warfarin

- Oral hypoglycaemics such as sulphonylureas

- Phenytoin

Other drugs subject to metabolism by CYP3A4;

- HIV Protease Inhibitors such as saquinavir;

- Certain antineoplastic agents such as vinca alkaloids, busulfan and docetaxel;

- Certain calcium channel blockers such as dihydropyridines and verapamil;

- Certain immunosuppressive agents: cyclosporin, tacrolimus, sirolimus (= rapamycin)

- Others: , carbamazepine, cilostazol, disopyramide, buspirone, alfentanil, sildenafil, alprazolam, brotizolam, midazolam IV, rifabutin, methylprednisolone, trimetrexate, ebastine and reboxetine.

In animals, miconazole has shown no teratogenic effects but is foetotoxic at high oral doses. The significance of this to man is unknown. However, as with other imidazoles, Daktarin Oral Gel should be avoided in pregnant women if possible. The potential hazards should be balanced against the possible benefits.

It is not known whether miconazole is excreted in human milk. Caution should be exercised when prescribing Daktarin Oral Gel to nursing mothers.

Daktarin should not affect alertness or driving ability.

The safety of Daktarin Oral Gel was evaluated in 111 patients with oral candidiasis or oral mycoses who participated in 5 clinical trials. Of these 111 patients, 88 were adults with oral candidiasis or oral mycoses who participated in 1 randomised, activecontrolled, double-blind clinical trial and 3 openlabel clinical trials. The other 23 patients were paediatric patients with oral candidiasis who participated in 1 randomised, activecontrolled, openlabel clinical trial in paediatric patients (aged 1 month to 10.7 years). These patients took at least one dose of Daktarin Oral Gel and provided safety data.

Based on the pooled safety data from these 5 clinical trials (adult and paediatric), the most commonly reported (1% incidence) ADRs were nausea (6.3%), product taste abnormal (3.6%), vomiting (3.6%), oral discomfort (2.7%), regurgitation (1.8%), and dry mouth (1.8%). Dysgeusia was reported in 0.9% of patients.

Table A includes all identified ADRs, including those that that have been reported from post-marketing experience.

The frequency categories use the following convention: very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available clinical trial data).

Adult Patients

Based on the pooled safety data from the 4 clinical trials in adults, common ADRs reported included nausea (4.5%), product taste abnormal (4.5%), oral discomfort (3.4%), dry mouth (2.3%), dysgeusia (1.1%), and vomiting (1.1%).

Paediatric Patients

In the 1 paediatric clinical trial, the frequency of nausea (13.0%) and vomiting (13.0%) was very common, and regurgitation (8.7%) was common. As identified through post-marketing experience, choking may occur in infants and young children (See Section 4.3 Contraindications and Section 4.4 Special Warnings and Special Precautions). The frequency, type, and severity of other ADRs in children are expected to be similar to that in adults.

Table A: Adverse Drug Reactions in Patients Treated with DAKTARIN Oral Gel or Tablets

Symptoms:

In the event of accidental overdose, vomiting and diarrhoea may occur.

Treatment:

Treatment is symptomatic and supportive. A specific antidote is not available.

In the event of accidental ingestion of large quantities of Daktarin an appropriate method of gastic emptying may be used, if considered necessary (See Section 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction.)

ATC Code: A01A B09 and A07A C01

Miconazole possesses an antifungal activity against the common dermatophytes and yeasts as well as an antibacterial activity against certain gram-positive bacilli and cocci.

Its activity is based on the inhibition of the ergosterol biosynthesis in fungi and the change in the composition of the lipid components in the membrane, resulting in fungal cell necrosis.

Absorption:

Miconazole is systemically absorbed after administration as the oral gel. Administration of a 60 mg dose of miconazole as the oral gel results in peak plasma concentrations of 31 to 49 ng/mL, occurring approximately two hours post-dose.

Distribution:

Absorbed miconazole is bound to plasma proteins (88.2%), primarily to serum albumin and red blood cells (10.6%).

Metabolism and Elimination:

The absorbed portion of miconazole is largely metabolized; less than 1% of an administered dose is excreted unchanged in the urine. The terminal half-life of plasma miconazole is 20 to 25 hours in most patients. The elimination half-life of miconazole is similar in renally impaired patients. Plasma concentrations of miconazole are moderately reduced (approximately 50%) during hemodialysis. About 50% of an oral dose may be excreted in the faeces partly metabolized and partly unchanged.

Preclinical data reveal no special hazard for humans based on conventional studies of local irritation, single and repeated dose toxicity, genotoxicity, and toxicity to reproduction.

Purified water

Pregelatinised potato starch

Alcohol

Polysorbate 20

Sodium saccharin

Cocoa flavour

Orange flavour

Glycerol

None known.

3 years.

Do not Store above 30°C.

Aluminium tubes containing 5 g*, 15 g*, 30 g* 40 *g or 80 g gel.

A 5 ml plastic spoon, marked with a 2.5 ml graduation is provided.

* not marketed

Not applicable.

Janssen-Cilag Limited

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PL 0242/0048

Date of First Authorisation: 19 July 1977

Date of Renewal of Authorisation: 22 May 2008

15 September 2010