Daktarin Oral Gel

Oral treatment of candidosis of the oropharynx.

Miconazole gel is for use in adults, children and infants 4 months and older.

For oral administration.

The provided measuring device is equivalent to 122 mg for 5 ml.

Oropharyngeal candidosis

Infants: 4-24 months: 1.25 ml (1/4 measuring spoon) of gel, applied four times a day after meals. Each dose should be divided into smaller portions and the gel should be applied to the affected area(s) with a clean finger. The gel should not be applied to the back of the throat due to possible choking. 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: 2.5 mL (1/2 measuring spoon) of gel, applied four times a day after meals.

The gel should not be swallowed immediately, but kept in the mouth as long as possible.

The treatment should be continued for at least a week after the symptoms have disappeared.

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

Known hypersensitivity to miconazole, other imidazole derivatives or to any of the excipients listed in section 6.1.

In infants less than 4 months of age or in those whose swallowing reflex is not yet sufficiently developed (see section 4.4).

In patients with liver dysfunction.

Coadministration of the following drugs that are subject to metabolism by CYP3A4 (see section 4.5):
- 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

Miconazole is systemically absorbed and is known to inhibit CYP2C9 and CYP3A4 (see section 5.2) which can lead to prolonged effects of warfarin. Bleeding events, some with fatal outcomes, have been reported with concurrent use of miconazole oral gel and warfarin (see section 4.5 and section 4.8). If the concomitant use of miconazole oral gel with oral coumarin anticoagulants such as warfarin is planned, caution should be exercised and the anticoagulant effect must be carefully monitored and titrated (see section 4.5).

Patients should be advised that if they experience unexpected bleeding or bruising, nosebleeds, coughing up blood, blood in the urine, black tarry stools or coffee ground vomit, to stop treatment with miconazole and seek medical advice.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with miconazole (see section 4.8). If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued.

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).

Choking in infants and young children

Particularly in infants and young children (aged 4 months – 2 years), 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. Each dose should be divided into smaller portions and applied into the mouth with a clean finger. Observe the patient for possible choking. Also due to the risk of choking, the gel must not be applied to the nipple of a breastfeeding woman for administration to an infant.

It is important to take into consideration the variability of the maturation of the swallowing function in infants, especially when giving miconazole gel to infants between the ages of 4-6 months. The lower age limit should be increased to 5-6 months of age for infants who are pre-term, or infants exhibiting slow neuromuscular development.

Serious skin reactions (e.g. Toxic epidermal necrolysis and Stevens‑Johnson syndrome) have been reported in patients receiving miconazole (see section 4.8). It is recommended that patients be informed about the signs of serious skin reactions, and that use of miconazole be discontinued at the first appearance of skin rash.

If symptoms persist or get worse, or if new symptoms occur, stop use and consult a doctor.

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

This medicine contains 23 mg of alcohol (ethanol) in each 2.5 ml dose corresponding to 7.5 mg/g. The amount in each 2.5 ml dose is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will not have any noticeable effects.

This medicine contains benzyl benzoate which may cause allergic reactions.

This medicine contains 2.3 picograms of benzyl alcohol per gram. Benzyl alcohol may cause allergic reactions and mild local irritation. Benzyl alcohol has been linked with the risk of severe side effects including breathing problems (called “gasping syndrome”) in young children. Do not give to your newborn baby (up to 4 weeks old), unless recommended by your doctor. Do not use for more than a week in young children (less than 3 years old), unless advised by your doctor or pharmacist. Ask your doctor or pharmacist for advice if you are pregnant or breast‑feeding. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”). Ask your doctor or pharmacist for advice if you have a liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).

This medicine contains polysorbate which can cause allergic reactions.

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):
• 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):
• 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.

Pregnancy

At clinically relevant exposures, animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of miconazole during pregnancy unless the benefit of therapy to the patient is considered to outweigh the risks to the foetus.

Lactation

It is not known whether miconazole or its metabolites are excreted in human milk. Caution should be exercised when prescribing miconazole oral gel to nursing mothers.

Patients who are pregnant or breastfeeding should seek advice from a doctor before using miconazole oral gel.

It is not known if miconazole has an effect on the ability to drive or use machines.

The safety of miconazole 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 miconazole 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) adverse reactions 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.

Adult Patients

Based on the pooled safety data from the 4 clinical trials in adults, common adverse reactions 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 and section 4.4). The frequency, type, and severity of other adverse reactions in children are expected to be similar to that in adults.

Description of selected adverse reactions

Increases in INR and bleeding events such as epistaxis, contusion, haematuria, melaena, haematemesis, haematoma and haemorrhages have been reported in patients treated with oral anticoagulants such as warfarin in association with miconazole oral gel (see sections 4.4 and 4.5). Some events had fatal outcomes.

Table A includes all identified adverse reactions, including those 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).

Table A: Adverse Drug Reactions in Patients Treated with Miconazole Oral Gel

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms

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

Treatment

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

Keep out of reach of children. In the event of overdose, get medical help straight away.

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 oral administration. Administration of a 60 mg dose of miconazole 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%). The apparent volume of distribution in man is about 1400L.

Metabolism

Miconazole is metabolized in the liver to inactive metabolites. The absorbed portion of miconazole is largely metabolized; less than 1% of an administered dose is excreted unchanged in the urine.

Elimination

Miconazole is eliminated largely in the faeces and urines as inactive metabolites. Approximately 10% to 20% of the oral dose is excreted in the urine, however, only 1% of the administered dose is present as unchanged miconazole. About 50% of a dose taken orally is excreted in the faeces. Plasma miconazole has been described as having triphasic elimination pharmacokinetics with a short initial half-life of less than 1 hour, an intermediate half-life of 2 hours and a terminal half-life of 20 to 25 hours in most patients.

Renal Impairment

The elimination half-life of miconazole is similar in renally impaired patients.

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.

In animals, miconazole has shown no teratogenic effects but is fetotoxic at high oral doses. The significance of this to man is unknown.

Glycerol

Ethanol

Carbomers

Polysorbate 20 (E432)

Saccharin sodium (E954)

Sodium hydroxide

Cocoa flavour (contains benzyl alcohol, benzyl benzoate and ethanol)

Orange flavour

Purified water

None known

Before opening: 3 years.

After first opening: Discard once the treatment for one episode of fungal infection is completed

Do not store above 30°C

This medicine is a white, homogenous gel. It is packed in 15 g, 40 g or 80 g aluminium tubes and closed with a polypropylene screw cap.

Not all pack sizes may be marketed.

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

Not applicable