Daktarin Oral Gel

Miconazole.

Each gram contains 20 mg of miconazole.
Excipients/Inactive Ingredients: The inactive ingredients of the oral gel are: alcohol, cocoa flavor, glycerol, orange flavor, pregelatinized potato starch, polysorbate, purified water, and sodium saccharin.

Pharmacotherapeutic Group: Antiinfectives and antiseptics for local oral treatment and Imidazole derivatives. ATC Code: A01A B09 and A07A C01.
Pharmacology: Pharmacodynamics: Mechanism of action: Miconazole possesses an antifungal activity against the common dermatophytes and yeasts as well as an antibacterial activity against certain gram-positive bacilli and cocci.
Miconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in the membrane, resulting in fungal cell necrosis.
Pharmacokinetics: 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: The absorbed portion of miconazole is largely metabolized; less than 1% of an administered dose is excreted unchanged in the urine.
Elimination: The terminal half-life of plasma miconazole is 20 to 25 hours in most patients.
Special populations: 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.
Toxicology: Non-clinical information: 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.

Treatment of candidosis of the oropharyngeal cavity and the gastrointestinal tract in adults and pediatric patients 6 months and older (see Contraindications and Precautions).

Oropharyngeal candidosis: Infants: 6-24 months: 1.25 mL (1/4 teaspoon) of gel, applied four times a day after meals. Each dose is to be divided into smaller portions and the gel applied to the affected area(s) with a clean finger. The gel is not to 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 teaspoon) of gel, applied four times a day after meals. The gel is not to be swallowed immediately, but kept in the mouth as long as possible.
Continue the treatment for at least a week after the symptoms have disappeared.
For oral candidosis, dental prostheses are to be removed at night and brushed with the gel.
Gastrointestinal tract candidosis: The gel may be used for infants (≥ 6 months of age), children, and adults who have difficulty swallowing tablets. The dosage is 20 mg per kg body weight per day, administered in 4 divided doses. The daily dose should not exceed 250 mg (10 mL Oral Gel) four times a day.
Continue the treatment for at least a week after the symptoms have disappeared.

Symptoms and signs: In the event of accidental overdose, vomiting and diarrhea may occur.
Treatment: Treatment is symptomatic and supportive. A specific antidote is not available.

DAKTARIN Oral Gel is contraindicated in the following situations: In patients with hypersensitivity to miconazole, another ingredient of the formulation, or other imidazole derivatives.
In infants less than 6 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: (See Interactions): Substrates known to prolong the QT-interval for example, astemizole, bepridil, cisapride, dofetilide, halofantrine, mizolastine, pimozide, quinidine, sertindole and terfenadine; Ergot alkaloids; HMG-CoA reductase inhibitors such as simvastatin and lovastatin; Triazolam and oral midazolam.
Use of miconazole oral gel in combination with the following drug that is subject to metabolism by CYP2C9 (see Interactions): Warfarin.

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 (see Interactions).
It is important to take into consideration the variability of the maturation of the swallowing function in infants.
Particularly in infants and young children (aged 6 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 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 breast-feeding woman for administration to an infant.
Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with DAKTARIN Oral Gel (see Adverse Reactions). If a reaction suggesting sensitivity should occur, the treatment should be discontinued.
Serious skin reactions (e.g. Toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported in patients receiving DAKTARIN Oral Gel (see Adverse Reactions). It is recommended that patients be informed about the signs of serious skin reactions, and that use of DAKTARIN Oral Gel be discontinued at the first appearance of skin rash.
Effects on Ability to Drive and Use Machines: DAKTARIN Oral Gel does not affect alertness or driving ability.

Pregnancy: 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 Oral Gel during pregnancy unless the benefit of therapy to the patient is considered to outweigh the risks to the fetus.
Breast-feeding: It is not known whether miconazole or its metabolites are excreted in human milk (see Precautions).

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of miconazole based on the comprehensive assessment of the available adverse event information. A causal relationship with miconazole cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of DAKTARIN Oral Gel was evaluated in 88 adult patients with oral candidiasis or oral mycoses who participated in one randomized, active-controlled, double-blind clinical trial and three open-label clinical trials. These patients took at least one dose of DAKTARIN Oral Gel and provided safety data.
Adverse reactions reported by DAKTARIN Oral Gel-treated adult patients in the four clinical trials are shown in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

The safety of DAKTARIN Oral Gel was evaluated in 23 pediatric patients with oral candidiasis who participated in one randomized, active-controlled, open-label clinical trial in pediatric patients aged ≤ 1 month to 10.7 years. These patients took at least one dose of DAKTARIN Oral Gel and provided safety data.
Adverse reactions reported by DAKTARIN Oral Gel-treated pediatric patients in the one clinical trial are presented in Table 2. (See Table 2.)

Click on icon to see table/diagram/image

Postmarketing Data: In addition to the adverse reactions reported during clinical studies and listed previously, the following adverse reactions have been reported during postmarketing experience (Table 3). In each table, the frequencies are provided according to the following convention: Very common ≥1/10; Common ≥1/100 and < 1/10; Uncommon ≥1/1,000 and <1/100; Rare ≥1/10,000 and <1/1,000; Very rare <1/10,000, including isolated reports.
In Table 3, adverse reactions are presented by frequency category based on spontaneous reporting rates. (See Table 3.)

Click on icon to see table/diagram/image

When using any concomitant medication, consult the corresponding label for information on the route of metabolism. 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 drugs that are subject to metabolism by CYP3A4 (see Contraindications): Substrates known to prolong the QT-interval for example, astemizole, bepridil, cisapride, dofetilide, halofantrine, mizolastine, pimozide, quinidine, sertindole and terfenadine; Ergot alkaloids; HMG-CoA reductase inhibitors such as simvastatin and lovastatin; Triazolam and oral midazolam.
Miconazole oral gel is contraindicated with the co-administration of the following drug that subject to metabolism by CYP2C9 (see Contraindications): Warfarin.
When co administered 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 (see Precautions): Oral hypoglycemics 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 immunosuppressive agents: cyclosporine, tacrolimus, sirolimus (rapamycin); Others: alfentanil, alprazolam, brotizolam, buspirone, carbamazepine, cilostasol, disopyramide, ebastine, methylprednisolone, midazolam IV, reboxetine, rifabutin, sildenafil, and trimetrexate.

Instructions for Use and Handling: To open the tube, unscrew the cap and pierce the seal of the tube using the pin on the top of the cap.
Incompatibilities: None known.

Store below 30°C.
Protect from light.
Shelf-Life: 3 years.

Oropharyngeal anti-infectives

A01AB09 - miconazole ; Belongs to the class of local antiinfective and antiseptic preparations. Used in the treatment of diseases of the mouth.

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