Klindaket
Composition:
Each Ovules (Pessaries) contains:
Clindamycin Phosphate USP 118.88 mg Equivalent to Clindamycin 100.00 mg Ketoconazole BP 400 mg
Ovules (Pessaries) base Q.S.
Excipient: Witepsol H-15
Pharmacotherapeutic group: Lincosamide and Imidazole derivatives ATC Code: J01FF01, J02AB02
Pharmacological properties:
Clindamycin phosphate mechanism of action: Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Ketoconazole mechanism of action: Ketoconazole is a steroidogenesis inhibitor. Ketoconazole is an imidazole derivative that is a potent inhibitor of cortisol synthesis resulting from its ability to inhibit several cytochrome P450 enzymes in the adrenal glands. Ketoconazole inhibits primarily the activity of 17α-hydroxylase, but it also inhibits 11-hydroxylation steps, and at higher doses the cholesterol side-chain cleavage enzyme. Therefore, ketoconazole is an inhibitor of cortisol and aldosterone synthesis. Ketoconazole is also a potent inhibitor of androgens synthesis, inhibiting the activity of C17-20 lyase in the adrenals and also in Leydig cells.
Pharmacokinetics: Clindamycin USP 100 mg and Ketoconazole BP 400 mg Ovules (Pessaries) is clindamycin plus ketoconazole in a formulation for vaginal administration in pessary, with both antibacterial and antifungal action, specially designed for the etiological treatment of vaginal infections more common in women, bacterial vaginosis, vaginal candidiasis and mixed vaginitis. Clindamycin is a semisynthetic derivative of lincomycin with antibiotic action against various strains of aerobic gram positive microorganisms such as Gardnerella vaginalis and Streptococcus viridians, microaerophilic gram-negative and anaerobic bacteria such as Bacteroides fragilis, Mobiluncus spp, Fusobacterium, within which are the germs responsible of bacterial vaginosis. Clindamycin phosphate is inactive until hydrolyzed to free clindamycin result, phosphatase enzymes in the vaginal mucosa rapidly hydrolyze the drug after topical application. Clindamycin has bactericidal action solely because it binds to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. When administered clindamycin ovule formulation of systemic absorption is reached on average 30%, compared with the vaginal cream that reaches only 4%. The distribution and elimination after intravaginal application have not been fully identified, however, the systemic half-life seems to be between 1.5 and 2.6 hours and is eliminated by self-cleansing mechanisms of the vagina. Ketoconazole is an antifungal azole group, a synthetic derivative of imidazole with fungistatic and fungicidal actions depending on the dose. Like others in this group antifungal, ketoconazole inhibits ergosterol synthesis by blocking the 14 alpha demethylase lanosterol-dependent cytochrome P-450 is necessary to convert lanosterol to ergosterol. Ergosterol is an essential component of the cytoplasmic membrane, by inhibiting its synthesis is altered membrane permeability leading to increased resulting in a loss of cellular components, producing a fungistatic action. At higher concentrations, ketoconazole may have a direct physicochemical action on the cell membrane mycetes, exerting a fungicidal action. Ketoconazole in vitro, prevents the formation of Candida pseudohyphae in facilitating the polymorphonuclear phagocytosis of the fungus. Ketoconazole is a broad spectrum of activity including yeasts and dermatophytes. Yeast: Candida albicans, C. tropicalis, Malassezia ovale. Dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouinii, M. gypseum and Epidermophyton floccosum Ketoconazole applied vaginally has minimal systemic absorption. Plasma concentrations in women receiving 400 mg of ketoconazole ranging from 4 to 20.7 ug / ml. Because ketoconazole applied vaginally hardly reaches the circulation, does not undergo biotransformation and is eliminated by self-cleansing mechanisms of the vagina.
Therapeutic indications:
Treatment of bacterial and fungal vaginal infection. Clindamycin USP 100 mg and Ketoconazole BP 400 mg Ovules (Pessaries) for antibiotic action is indicated for the treatment of bacterial vaginosis caused by Bacteroides spp, Gardnerella vaginalis, Mobiluncus spp, Mycoplasma hominis and other anaerobes. Because of its antifungal action is indicated for the treatment of vaginal candidiasis and mixed vaginitis. Instructions for use: Clindamycin USP 100 mg and Ketoconazole BP 400 mg Ovules (Pessaries) is administered through the vagina once a day preferably at night at bedtime for 7 consecutive days in pregnant patients and 5 days non pregnant patient, except better opinion of the treating physician.
Contraindications:
History of hypersensitivity to clindamycin, lincomycin, ketoconazole, azole antifungal and any components of the formula.
Special instructions and precautions:
Warnings: Sexual abstinence is recommended during treatment with this product, avoid douching, and tampon use. Use in Pregnancy and Lactation: No adequate and well controlled studies in pregnant women during the first quarter. Because animal reproduction studies are not always forecast the human response, this drug should not be used during the first trimester of pregnancy unless the doctor's opinion absolutely necessary. Lactation: It is not known whether clindamycin or ketoconazole are excreted in human milk after vaginal administration due to low absorption. However, with oral or parenteral, has detected the presence of clindamycin and ketoconazole in breast milk. Hence it is decided to discontinue nursing or treatment. Interaction with other drugs: Clindamycin shows cross-resistance to lincomycin in vitro and antagonistic effect with erythromycin.
Use during pregnancy and lactation:
Do not administer during the first quarter pregnancy or breastfeeding. Systemic absorption of clindamycin as both ketoconazole applied vaginally is minimal. It has been reported that ketoconazole and clindamycin administered vaginally are carcinogenic or teratogenic, they have no effect on fertility.
Effects on the ability to drive a vehicle and other potentially dangerous mechanisms:
Not available.
Side effects:
The administration of clindamycin vaginal has been linked to the following clinical manifestations: In genital tract: Cervicitis / vaginitis symptomatic candidiasis, vaginal trichomoniasis and vulvar irritation. With the administration of ketoconazole vaginal been reported few cases of local irritation, itching and burning, especially at the beginning of treatment. Systemic absorption of clindamycin as both ketoconazole applied vaginally is minimal and thus systemic adverse reactions are minimal.
Overdose:
There are no reports regarding the presence of overdose with this product.
Storage:
Store below 25°C. Store in a cool dry place and protected from light.
KEEP THE MEDICINE OUT OF REACH OF CHILDREN.
PRESCRIPTION ONLY MEDICINE
Manufactured for:
OPES HEALTHCARE UK LIMITED 71-75 Shelton Street, London, England, United Kingdom, WC2H 9JQ at OPES HEALTHCARE PRIVATE LIMITED Ahmedabad, Gujarat, India.