McNeil Healthcare (Ireland) Ltd

DAKTARIN 20mg/g Oral Gel

Each 5 ml contains 124 mg of miconazole.

Each gram contains 20 mg miconazole.

Exipients-contains Ethanol 96% 7.59 mg/g

For a full list of excipients, see 6.1.

Oral gel.

White homogeneous gel having an orange taste.

In the management, including prophylaxis, of fungal infections of the oral cavity and gastro-intestinal tract.

Miconazole is effective against some Gram positive bacteria, including Streptococcus pyrogenes, Staphylococcus aureus and Erysipelothrix.

For oral administration.

Infants: 6-24 months: 1.25ml (1/4 measuring spoon) of gel, applied four times a day. Each dose should be divided into smaller portions and the gel should be applied to the affected area(s). The gel should not be swallowed immediately, but kept in the mouth as long as possible.

Adults and children 2 years of age and older: 2.5ml (1/2 measuring spoon) of gel, applied four times a day. The gel should not be swallowed immediately, but kept in the mouth as long as possible.

The treatment should be continued for at least two days after the symptoms have disappeared.

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 6 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

The anticoagulant effect should be carefully monitored if Daktarin and oral anticoagulants such as warfarin are used at the same time.

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).

Caution is required, particularly in infants and young children, to ensure that the gel does not obstruct the throat. Each dose should be divided into smaller portions for application and the patient observed for possible choking. The gel should not be applied to the back of the throat.

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, bulsulfan 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 animal studies, miconazole has not shown teratogenic effects, but is foetotoxic at high oral doses. The significance of this in relation to man is not known.

Safety in human pregnancy has not been established and the drug should not be used in pregnant women unless considered absolutely essential by the physician. 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, active-controlled, double-blind clinical trial and 3 open-label clinical trials. The other 23 patients were paediatric patients with oral candidiasis who participated in 1 randomised, active-controlled, open-label 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

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 gasrtic 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, including (Staphylococcus and Streptococcus spp)..

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 (based on 19 patients with renal impairment). Plasma concentrations of miconazole are moderately reduced (approximately 50%) during hemodialysis.

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.

Pregelatinised potato starch

Ethanol

Polysorbate 20 (E432)

Sodium saccharin

Cocoa flavour

Orange flavour

Glycerol

Purified water

Not applicable.

3 years.

Do not store above 30°C.

An aluminium collapsible membrane tube, with polypropylene screw cap containing 40 g gel.

A 5 ml plastic spoon, marked with a ¼ and ½ spoon graduations (1.25 & 2.5 ml) is provided.

No special requirements.

McNeil Haeltcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

823/59/3

10 July 1979/10 July 2009

May 2010