Fluomizin

Dequalinium chloride.

Each vaginal tablet contains 10 mg dequalinium chloride.
Dequalinium chloride is an antiinfective and antiseptic agent belonging to the class of quaternary ammonium compounds. This drug substance has a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts, and protozoa, including all relevant vaginal pathogens.
Excipients/Inactive Ingredients: Lactose monohydrate, Cellulose, microcrystalline (E460a), Magnesium stearate (E470b).

Pharmacotherapeutic Group: Gynaecological anti-infective and antiseptic, Quinolone derivatives. ATC Code: G01A C05.
Pharmacology: Pharmacodynamics: Dequalinum chloride is an anti-infective and antiseptic agent belonging to the class of quaternary ammonium compounds.
Mode of action: Dequalinium chloride is a surface-active substance. The primary mode of action is an increase in bacterial cell permeability and the subsequent loss of enzyme activity, finally resulting in cell death.
Dequalinium chloride exhibits a rapid bactericidal activity.
Dequalinium chloride in vaginal tablets exerts its action locally within the vagina.
PK/PD Relationship: No major PK/PD determinant of efficacy has been established for Fluomizin. As the bactericidal effect of dequalinium chloride occurs within 30 to 60 minutes, the maximum local concentration within the first hour after application is considered crucial for the efficacy.
Mechanism(s) of resistance: The mechanisms resulting in the inherent resistance of some pathogens are not known. No mechanisms of acquired resistance have been observed thus far.
Breakpoints: No Breakpoints for dequalinium chloride are available by any recommending body and no relationship between minimal inhibitory concentrations and the clinical efficacy has been established. Thus, the information on susceptibility in the table as follows is descriptive and is based on the concentrations achievable in the vagina (see Pharmacology: Pharmacokinetics as follows) and respective MIC data of the pathogens.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable. (See Table 1.)


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The in vitro activity of dequalinium chloride against the following vaginally important microorganisms was established and expressed as Minimum Inhibition Concentration (MIC). (See Table 2.)


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Pharmacokinetics: After dissolution of a Fluomizin vaginal tablet (10 mg dequalinium chloride) in an estimated 2.5 to 5 ml of vaginal fluid, the dequalinium chloride concentration in the vaginal fluid is 2000-4000 mg/l.
Preclinical data indicate that dequalinium chloride is absorbed only to a very small amount after vaginal application. Therefore, systemic exposure to Fluomizin is negligible and not further pharmacokinetic data are available.
Toxicology: Preclinical safety data: Systemic toxic effects of Fluomizin are unlikely on the basis of the negligible systemic exposure of dequalinium chloride administered intravaginally.
In vivo and in vitro studies with dequalinium chloride did not yield any indication of a potential to cause mutagenicity.
No reproduction toxicity studies have been conducted with dequalinium chloride.
A study in rabbits showed the good vaginal tolerance of Fluomizin.

Vaginal infections of bacterial and mycotic origin (e.g. bacterial vaginosis and candidiasis); trichomoniasis; achievement of asepsis before gynaecological operations and deliveries.

One vaginal tablet daily for six days.
The vaginal tablets should be inserted deeply into the vagina in the evenings before retiring. This is best performed in a reclining position with the legs slightly bent.
The treatment should be interrupted during menstruation and resumed afterwards.
Although relief of discharge and inflammation generally occurs within 24 to 72 hours, the treatment should be continued even when there is no subjective discomfort (itching, discharge, smell) anymore. A treatment less than six days could result in a relapse.
For use in women under 18 years and more than 55 years see Precautions.
Route of administration: vaginal use.

No case of overdose has been reported. However, use a higher daily dose might result in vaginal ulcerations.

Hypersensitivity to the active substance or to any of the excipients; Ulceration of the vaginal epithelium and portio vaginalis uteri; Young girls who have not yet had their first menstruation, and thus did not reach sexual maturity must not use Fluomizin.

To minimize exposure of the newborn to dequalinium chloride, vaginal tablets should not be used within 12 hours before birth.
There are no efficacy and safety data on the re-treatment of patients who did not respond to or relapsed immediately after initial therapy with Fluomizin.
Using a higher daily dose or increasing the recommended treatment duration might increase the risk of vaginal ulcerations.
No efficacy and safety data on the treatment of bacterial vaginosis in women aged 18 years or more than 55 years are available.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.

Pregnancy: Four clinical studies involving 181 pregnant patients did not demonstrate any adverse effect on the pregnancy or on the foetus/neonate. Furthermore, considerable post-marketing experience indicates no malformative or feto/neonatal toxicity of Fluomizin.
No reproductive toxicity studies have been conducted in animals because of the expected low systemic exposure to dequalinium chloride after vaginal administration.
The use of Fluomizin may be considered during pregnancy, if necessary.
Lactation: Systemic exposure of the breast-feeding women to Fluomizin is negligible. Therefore, no harmful effects on the breastfed newborn/infant are anticipated.
Fluomizin can be used during lactation if clinically needed.
To minimize exposure of the newborn to dequalinium chloride, vaginal tablets should not be used within 12 hours before birth.

In clinical trials, the following undesirable effects possible or probably related to dequalinium chloride have been reported.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table 3.)


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During post-marketing experience the following undesirable effects have been reported (frequency unknown): Reproductive system and breast disorders: ulceration and maceration of vaginal epithelium, uterine bleeding, redness, vaginal dryness.
Infections and infestations: cystitis.
General disorders and administration site conditions: fever, allergic reactions.

Anionic substances such as soaps, detergents and surfactants can reduce the antimicrobial activity of dequalinium chloride. Thus, concomitant intravaginal use of soaps, spermicides or vaginal douches (vaginal washes) is not recommended.
Fluomizin 10 mg vaginal tablets do not impair the functionality of latex condoms. There are no data on the interaction with non-latex condoms and other intravaginal devices such as diaphragms. Thus, concomitant use of non-latex condoms and other intravaginal devices is not recommended.

Special precautions for disposal <and other handling>: Fluomizin contains excipients which do not dissolve completely, such that remains of the tablet are occasionally found in the underwear. This is of no importance for the efficacy of Fluomizin.
In rare cases of a very dry vagina, it is possible that the vaginal tablet does not dissolve and is discharged by the vagina as intact tablet. As consequence, the treatment is not optimal. For prevention, the vaginal tablet can be moistened with a drop of water before insertion into a very dry vagina.
Patients should use a sanitary towel or panty liner. There is no change in colour of the underwear. Patients should be instructed to change their underwear and flannel daily and launder them at a temperature of at least 80°C.
Incompatibilities: Fluomizin is incompatible with soaps and other anionic surfactants.

Do not store above 30°C.
Shelf-Life: 3 years.

Preparations for Vaginal Conditions

G01AC05 - dequalinium ; Belongs to the class of quinolone derivative antiinfectives. Used in the treatment of gynecological infections.