DAKTARIN Oral gel

- in patients with 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

- Use in combination with the following drugs that are subject to metabolism by CYP3A4.

- Substrates known to prolong the QT-interval for example, astemizole, bepridil,. cisapride, dofetilide, halofantrine, mizolastine, pimozide, quinidine, sertinodole and terfenadine

- Ergot alkaloids

- HMG-CoA reductase inhibitors such as simvastatin and lovastatin

- Triazolam and oral midazolam

Miconazole can inhibit the metabolism of drugs metabolized 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 drops that are subject to metabolism by CYP34.

 Substrates known to prolong the QT-interval for example astemizole, bepridil, cisapride, dofetilide, halofantrine, mizolastine, primozide, quinidine, sertinodole 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 must be used with caution because of a possible increase or prolongation of the therapeutic outcome and/or adverse effects.

If necessary, reduce their dosage and, where appropriate, monitor plasma levels:

 Drugs subject to metabolism by CYP2C9:

- Oral Anticoagulants such as warfarin

- Oral hypoglycemic such as sulfonylureas

- 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 immnosuppressive agents: cyclosporine, tacrolimus, sirolimus (rapamycin)

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

There are no adequate and well-controlled studies in pregnant women. 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 DAKTARIN during pregnancy unless the benefit of therapy to the patient is considered to outweigh the risks to the fetus.

If the concomitant use of DAKTARIN and an oral anticoagulant such as warfarin is planned, the anticoagulant effect must be carefully monitored and titrated.

It is advisable to monitor miconazole and phenytoin levels, if these 2 drugs are used concomitantly.

In patients using certain oral hypoglycemics such as sulfonylureas, an enhanced therapeutic effect leading to hypoglycemia may occur during concomitant treatment with miconazole and appropriate measures must be considered.

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.

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 is not to be applied to the back of the throat. Each dose is to be divided into smaller portions and applied into the mouth with a clean finer. Observe the patient for possible choking. Also due to the risk of choking, the el must not be applied to the nipple of a breast-feeding woman for administration to an infant.

miconazole possesses an antifungal activity against the common dermatophytes and yeasts as well as an antibacterial activity against certain gam-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.