Gynoflor

Viable Lactobacillus acidophilus, estriol.

Each vaginal tablet contains viable Lactobacillus acidophilus 100 million and estriol 0.03 mg.
Gynoflor also contains the following excipients: Lactose, anhydrous disodium phosphate, microcrystalline cellulose, sodium starch glycolate and magnesium stearate.

Pharmacology: Pharmacodynamics: Lactobacillus acidophilus is one of the predominant microorganisms of the vaginal flora in healthy women. Lactobacilli are non-pathogenic bacteria and have a protective function in the vagina. It ferments glycogen stored in the vaginal epithelium to lactic acid. The resulting acidic environment (pH 3.8-4.5) provides unfavourable conditions for the colonisation and growth of pathogenic microorganisms and provides an optimal medium for the proliferation of the Lactobacilli. In addition to lactic acid, Lactobacilli produce hydrogen peroxide and bacteriocins which also inhibit the growth of pathogenic microorganisms.
Estriol is an endogenous estrogenic hormone which has a specific effect on the vagina but not on the endometrium. The purpose of the estriol in Gynoflor is to ensure proliferation and maturation of the vaginal epithelium. A proliferated and matured vaginal epithelium acts as physical barrier and stores glycogen, a nutritional substrate for Lactobacilli. In the case of hormonal disorders, more commonly observed at advanced age, the vaginal epithelium is disturbed and the glycogen content is decreased. Vaginal infections can also lead to a damaged vaginal epithelium.
Exogenous estriol, even in very low dose contained in Gynoflor, improves the proliferation and maturation of the epithelium and thus provides the optimal conditions for the restoration of the vaginal Lactobacilli flora.
Disturbance or elimination of the physiological vaginal flora can occur mainly as a result of local or systemic treatment with anti-infective agents, serious general illnesses, improper hygienic measures and vaginal infections. In a non-physiological vaginal environment, the Lactobacilli are reduced in number or even absent and the protective function is no longer assured.
The therapeutic concept of Gynoflor is based on the restoration of the vaginal flora through exogenous Lactobacilli and the improved proliferation and maturation of the vaginal epithelium by exogenous estriol, resulting in the reestablishment of the physiological equilibrium of the vaginal flora and the vaginal epithelium.
Lactobacillus acidophilus and estriol exert their actions locally within the vagina.
Lactose can also be fermented to lactic acid by the Lactobacilli. Reproduction of the Lactobacilli and re-colonisation of the vagina by these bacteria start after the 1st application of Gynoflor.
Pharmacokinetics: As soon as Gynoflor comes into contact with vaginal secretion, the tablet begins to disintegrate, and Lactobacilli as well as estriol are released. In vitro experiments have demonstrated that the Lactobacilli resume their metabolism and cause a reduction in pH within a few hours.
The positive estrogenic effect induced by estriol is also quickly initiated and the proliferation and maturation status of the vaginal epithelium improves progressively over the course of treatment (6-12 days).
The absorption of estriol from Gynoflor was investigated in healthy, postmenopausal women with atrophic epithelia. After a single intravaginal application of Gynoflor, there was an increase in the plasma concentration of unconjugated estriol (biologically active form) above the basal level and the maximum estriol concentration was reached after 3 hrs. After 8 hrs, the plasma concentration of unconjugated estriol was no longer elevated. However, after the 12th application at the end of the therapy with Gynoflor (once daily), the peak plasma level of unconjugated estriol was not elevated as compared to the basal level.
During the 12-day treatment, no accumulation of estriol was observed. The plasma concentrations observed after repeated application of Gynoflor were within normal range of the endogenous, postmenopausal plasma level of unconjugated estriol.
The plasma concentrations of estrone and estradiol are not affected by estriol therapy since estriol is their metabolic end-product. Estriol is eliminated rapidly in the urine, primarily in biologically inactive forms (glucuronides, sulphates).
Due to the low dose of estriol (0.03 mg), the local application and the limited duration of treatment (6-12 days), no accumulation of estriol occurs and systemic estrogen effects are very unlikely.
Toxicology: Preclinical Safety Data: Two toxicological aspects must be considered for drugs administered by the vaginal route, the local tolerance and the possibility of systemic toxicity due to absorption of the components.
Lactobacilli are the predominant microorganisms in the healthy human vagina and are regarded as non-pathogenic. For this reason, the introduction of these bacteria into the vagina is not expected to cause any local irritation or epithelial damage.
Results of animal experiments (Wistar rats) have demonstrated that only high doses of estriol can lead to a feminisation of the male foetus.
It should be noted that toxicological data obtained in rodents are of limited value and can not be extrapolated to man since estriol is specific for humans and does not occur in other mammalian species.
Considering the low dose of estriol in Gynoflor, no acute toxicity is to be expected.

For pathological vaginal discharge, restoration of the physiological Lactobacillus flora after local or systemic treatment with anti-infectives, vaginal infections caused by mixed flora, vaginal infections with Gardnerella vaginalis or Candida albicans (if antibacterial or antimycotic treatment is not absolutely necessary), atrophic vaginitis, pathological vaginal discharge during postmenopause eg, as co-medication accompanying estrogen substitution.

Pathological Vaginal Discharge, Vaginal Infections and Restoration of the Physiological Lactobacillus Flora: Insert 1-2 tablets deeply into the vagina in the evening before going to sleep. Treatment should be interrupted during menstruation and resumed afterwards. Duration of Treatment: 6-12 days.
Atrophic Vaginitis and Pathological Vaginal Discharge During Postmenopause: Insert 1 vaginal tablet deeply into the vagina in the evening before going to sleep. Duration of Treatment: 12 days.

No case of overdose has been reported.

Hypersensitivity to the dequalinium chloride or to any of the excipients of Gynoflor.
Malignant changes (estrogen-dependent tumours) in the breast, uterus or vagina; endometriosis (suspected or manifest); severely inflamed, suppurated, infiltrated vaginitis; vaginal haemorrhage of unknown origin; females who are not yet sexually mature.

Gynoflor contains only a small amount of estriol, and of this, only very little is absorbed. In addition, as Gynoflor is used only for a short period of time, there is minimal risk in the case of serious liver, heart and kidney function disturbances, epilepsy or migraine (also when reported in the anamnesis), hypertonia, diabetes mellitus, porphyria and hyperlipidemia. There is also minimal risk for patients with serious itching, rash or worsening otosclerosis during early pregnancy, and for those with thrombophlebitis or thromboembolic disorders in the anamnesis. However, during long-term treatment with Gynoflor, regular clinical check-ups should be performed for patients with the previously mentioned disorders, as for higher-dosed estrogen preparations, for safety reasons.
In the event of worsening of the previously mentioned disorders, recurrence of the mentioned symptoms or occurrence of thrombosis or jaundice, therapy with Gynoflor should be discontinued.
If bleeding takes place, therapy should be discontinued and the cause of bleeding determined.
Effects on the Ability to Drive or Operate Machinery: Not relevant.
Use in pregnancy: Experiments on animals have shown that estriol has an adverse effect on the foetus. There are no controlled trials on humans. Under these circumstances, Gynoflor should only be used if the potential benefits outweigh the foetal risk.
Due to the facts that Gynoflor contains a very low dose of estriol and that estriol is only minimally absorbed, adverse effects on the foetus when the preparation is used during pregnancy are improbable. In spite of this, Gynoflor should be used for the treatment of vaginal infections or for restoration of the Lactobacillus flora after anti-infective therapy only if such treatment is strictly indicated.
There is no indication for treatment with estriol alone during pregnancy.
Inform the physician if patient becomes pregnant during therapy with Gynoflor.
Use in lactation: There is not enough data on the application of estriol during lactation to be able to estimate possible risks for the newborn infant. However, it is known that estriol enters the mother's milk and can reduce the production of milk. However, considering the low dose and the minimal absorption of estriol after vaginal application, adverse effects on the infant are improbable.

Use in pregnancy: Experiments on animals have shown that estriol has an adverse effect on the foetus. There are no controlled trials on humans. Under these circumstances, Gynoflor should only be used if the potential benefits outweigh the foetal risk.
Due to the facts that Gynoflor contains a very low dose of estriol and that estriol is only minimally absorbed, adverse effects on the foetus when the preparation is used during pregnancy are improbable. In spite of this, Gynoflor should be used for the treatment of vaginal infections or for restoration of the Lactobacillus flora after anti-infective therapy only if such treatment is strictly indicated.
There is no indication for treatment with estriol alone during pregnancy.
Inform the physician if patient becomes pregnant during therapy with Gynoflor.
Use in lactation: There is not enough data on the application of estriol during lactation to be able to estimate possible risks for the newborn infant. However, it is known that estriol enters the mother's milk and can reduce the production of milk. However, considering the low dose and the minimal absorption of estriol after vaginal application, adverse effects on the infant are improbable.

General Disorders and Administration Site Conditions: A mild stinging or burning (1.6%) may be experienced shortly after the administration of Gynoflor. In rare cases, intolerability reactions eg, redness and itching have been reported. In one case, an allergy to the Lactobacillus lyophilisate contained in Gynoflor was observed.
If Gynoflor is accidentally administered orally, no adverse effects are to be expected.

Lactobacillus acidophilus is sensitive to various anti-infective agents (local or systemic). Simultaneous treatment of such agents may lead to a reduction in the efficacy of Gynoflor.
Inform the physician or pharmacist if patient is taking or has recently taken any other medications including those not prescribed.
Incompatibilities: Not applicable.

Instructions for Use/Handling: Gynoflor contains excipients which do not dissolve completely such that remains of the tablet are occasionally found in the underwear. This is of no importance to the efficacy of Gynoflor.
In rare cases of very dry vagina, it is possible that the vaginal tablet does not dissolve and is discharged by the vagina as an intact tablet. As a consequence, the treatment is not optimal. However, this is not harmful to the vagina. 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 and should not use vaginal douches or rinses during treatment.

Store in a refrigerator at 2-8°C. Storage of Gynoflor at room temperature during the treatment period (1-2 weeks) does not affect its efficacy.
Shelf-Life: 36 months.

Preparations for Vaginal Conditions

G01AX14 - lactobacillus ; Belongs to the class of other antiinfectives and antiseptics. Used in the treatment of gynecological infections.

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