Gestron
(Dydrogesterone Tablets USP)
COMPOSITION
Each film coated tablet contains
Dydrogesterone USP…….. 10mg. [USP Specs.]
Tablets
DESCRIPTION
GESTRON (Dydrogesterone) tablet is an orally-active progestogen which produces a complete secretory endometrium in an estrogen-primed uterus thereby providing protection against the increased risk for endometrium hyperplasia and/or carcinogenesis induced by estrogens.

INDICATIONS
Gestron is indicated for women with: Progesterone insufficiencies: Treatment of dysmenorrhoea, endometriosis, irregular menstrual cycles and pre-menstrual syndrome. Hormone replacement therapy: Dydrogesterone is used to supplement an estrogen treatment in non-hysterectomised women with symptoms due to natural onset of or surgically induced menopause. In the context of hormone replacement therapy, it counteracts the estrogen influence on the endometrium.
Dysfunctional bleeding or secondary amenorrhoea: The drug may be used with an estrogen in the management of these conditions.
DOSAGE AND ADMINISTRATION
The dosage, regimen and duration of treatment should be adjusted according to the severity of the symptoms and the clinical response.
Progesterone insufficiencies
Dysmenorrhoea: 10mg of dydrogesterone twice a day from day 5 to 25 of the cycle.. Endometriosis: 10mg of dydrogesterone two to three times daily from day 5 to 25 of the cycle, or continuously.
Irregular menstrual cycles: 10mg of dydrogesterone twice a day from day 11 to 25 of -the cycle.
Pre-menstrual syndrome: 10mg of dydrogesterone twice a day from day 12 to 26 of the cycle. The dosage may be increased if necessary.
Hormone replacement therapy: i.e. as supplement in estrogen treatment in non hysterectomised women with symptoms due to natural onset of or
surgically induced menopause
Continuous sequential therapy: continuous use of an estrogen; sequential supplementation of 10 mg dydrogesterone during the last 14 days of each 28 day cycle. Cyclical treatment: cyclic use of an estrogen with a treatment-free period, usually 21 days on and 7 days off treatment. For the last 12-14 days of estrogen use, 10mg of dydrogesterone is supplemented.
Depending on the clinical response, the dosage may be adjusted to 20mg dydrogesterone daily in the course of the treatment.
Dysfunctional uterine bleeding
When treatment is started to arrest a bleeding episode 10mg of dydrogesterone twice a day for five to seven days. For continuous treatment 10mg of dydrogesterone twice a day from day 11 to day 25 of the cycle. Withdrawal bleeding occurs if the endometrium has been adequately primed with either endogenous or exogenous estrogen.

Secondary amenorrhoea
10mg of dydrogesterone twice a day from day 11 to 25 to produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen. There is no relevant use for dydrogesterone before menarche. The safety and efficacy of dydrogesterone in adolescents aged 12-18 years has not been established.
Method of administration For oral use
When taking 1 film coated tablet daily, it is recommended to always take the daily dose at the same time of day, e.g. always in the morning or always in the evening. When taking 2 film coated tablets daily, it is recommended to take one in the morning and one in the evening.
-Contraindications for the use of estrogens should be taken into account when used in combination with dydrogesterone.
-Severe acute and chronic liver diseases as well as disorders in the metabolism of bile pigments (e.g. Dubin Johnson syndrome, Rotor syndrome). -Previous or existing liver tumours.
-Thrombophlebitis and thromboembolic diseases.
WARNINGS AND PRECAUTIONS
If dydrogesterone is prescribed for the treatment of irregular bleeding, the etiology of this bleeding should be clarified. Breakthrough bleeding and spotting may occur during the first months of treatment. If such bleeding occurs later in the course of the treatment or after the end of the treatment, the cause should be investigated and under some circumstances an endometrial biopsy should be performed to exclude endometrial malignancy.
Condition which need supervision
Patients should be closely monitored if any of the following situations or conditions are present or have previously been present or have worsened during pregnancy or previous hormone treatment. It should be considered that these situations or conditions may recur or worsen during therapy with dydrogesterone and discontinuation of treatment should be considered:
Porphyria – Depression – Pathological liver function values caused by acute or chronic liver disease – Cholestatic jaundice and/or pruritus.
Medical examinations/follow-up
Before starting or resuming HRT, a complete personal and family medical history should be obtained. The medical examination (including pelvic and breast examination) should be guided by information based on this medical history, as well as on the contraindications and precautions. Regular follow-up examinations are recommended during treatment, the frequency and nature of which are individual to each woman’s risk.
Endometrial hyperplasia and carcinoma
In women with an intact uterus the risk of endometrial hyperplasia and carcinoma is increased with long-term estrogen monotherapy. Adding a progestogen such as dydrogesterone cyclically for at least 12 days per month/28 day cycle or continuous combined estrogen-progestogen therapy in women with a uterus compensates for the additional risk posed by estrogen monotherapy.
Breast cancer
There is evidence of an increased risk of breast cancer in women receiving combined HRT with estrogen and progestogen or HRT containing estrogen alone, the risk depends on the duration of HRT.
Venous thromboembolism
HRT is associated with a 1.3-3-fold risk of venous thromboembolism (VTE), especially of deep vein thrombosis or pulmonary embolism. The Occurrence of such an event is much more likely in the first year of HRT use than later.
Ischemic stroke
Treatment with an estrogen-progestogen combination and estrogen alone is associated with up to a 1.5-fold increase in the risk of ischemic stroke. The relative risk is independent of age and the time elapsed since menopause. But since the baseline risk of stroke is highly depending on age, the overall risk of stroke in women under HRT will increase with age.

CLINICAL PHARMACOLOGY
Pharmacokinetics
Absorption: After oral administration, dydrogesterone is rapidly absorbed (Tmax between 0.5 and 2.5 hours). The absolute bioavailability of dydrogesterone (20mg orally versus 7.8mg by intravenous infusion) is 28%.
Distribution
After intravenous administration of dydrogesterone the steady-state volume of distribution is approximately 1,400 L. Dydrogesterone and DHD are more than 90% bound to plasma proteins.
Metabolism
Following oral administration, dydrogesterone is rapidly metabolized to DHD. The levels of the main active metabolite DHD peak about 1.5 hours post dose. The plasma level of DHD is substantially higher as compared to the parent drug. The ratios of DHD to dydrogesterone for AUC (area under the concentration-time-curve) and Cmax (maximum plasma concentration) are in the order of 40 and 25, respectively.
Elimination
After oral administration of labelled dydrogesterone, on average 63% of the dose is excreted into the urine. Total plasma clearance is 6.4 L/min.
CONTRAINDICATIONS
-Hypersensitivity to the active substance or to any of the excipients.
-Known or suspected progestogen-dependent tumours (e.g. meningioma) – Unexplained vaginal bleeding.
SIDE EFFECTS
The following are the side effects as described below. Common in the early phase of pregnancy: Loss of appetite, stomach pressure, nausea, oedema and weight gain, nervous restlessness, dizziness, worsening of mood and calf cramps. These complaints disappear when the treatment is stopped.
DRUG INTERACTIONS
In vitro data show that the pharmacologically active metabolite 200’61 dihydrodydrogesterone (DHD) is formed in the human cytosol by metabolic degradation by aldo-keto-reductase (AKR 1C). In addition to cytosolic metabolism, metabolic transformations occur via cytochrome P450 (CYP) isoenzymes – almost exclusively via CYP3A4, resulting in several secondary metabolites. The main active metabolite DHD is metabolically transformed by CYP3A4. Therefore, the metabolism of dydrogesterone and DHD may be increased when used concomitantly with substances known to induce CYP enzyme activity. These substances include anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine), preparations for the treatment of infections (e.g., rifampicin, rifabutin, nevirapine, efavirenz) and herbal preparations containing St John’s wort (Hypericum perforatum), sage or ginkgo biloba. Although ritonavir and nelfinavir are known to act as potent inhibitors of cytochrome enzymes, they have enzyme-inducing properties when used concomitantly with steroid hormones.
OVERDOSE
The available data with regard to overdose in humans are limited. Dydrogesterone has been well tolerated after oral administration (maximum daily dose in humans to date has been 360 mg). No specific antidotes are known. Treatment should be symptomatic. This information also applies to overdoses in children.
INSTRUCTIONS
Store below 30° C. Protect from heat, light and moisture. Keep out of the reach of children.
PRESENTATION: Gestron 10mg Tablets are available in pack sizes of 20’s.
ہدایات : ۳۰ ڈگری سینٹی گریڈ سے کم درجہ حرارت پر رکھیں۔ گرمی روشنی اور نمی سے بچائیں۔ بچوں کی پہنچ سے دور رکھیں ۔
Manufactured by:
NABIQASIM INDUSTRIES (PVT.) LTD.
PHARMA 17/24, Korangi Industrial Area, Karachi-Pakistan.