Monograph: |
DIENOGEST
DESCRIPTION
DIENOGEST IS AN ORALLY-ACTIVE SEMISYNTHETIC PROGESTOGEN WHICH ALSO POSSESSES THE PROPERTIES OF 17?-HYDROXYPROGESTERONE. IT IS A DERIVATIVE OF 19-NORTESTOSTERONE AND HAS ANTIANDROGENIC PROPERTIES. IT IS PRIMARILY USED AS A CONTRACEPTIVE IN COMBINATION WITH ETHINYLESTRADIOL, OR IN OTHER COMBINATION FORM PILLS APPROVED IN UNITED STATES AND EUROPE HOWEVER IT IS NOT AVAILABLE IN THE US BY ITSELF. IN EUROPE, AUSTRALIA, MALAYSIA, SINGAPORE AND JAPAN, DIENOGEST SINGLE THERAPY IS AN APPROVED TREATMENT FOR ENDOMETRIOSIS TO ALLEVIATE PAINFUL SYMPTOMS OF ENDOMETRIOSIS AND REDUCE ENDOMETRIOTIC LESIONS . DIENOGEST IS COMMONLY MARKETED AS VISANNE, NATAZIA AND QLAIRA.
PHARMACOLOGY
INDICATION
INDICATED FOR USE AS THE TREATMENT OF ENDOMETRIOSIS ALONE AND AS A CONTRACEPTIVE IN COMBINATION WITH ETHINYLESTRADIOL.
ASSOCIATED CONDITIONS
路 HYPERMENORRHEA
路 PAIN
ASSOCIATED THERAPIES
路 ORAL CONTRACEPTION
PHARMACODYNAMICS
DIENOGEST EXHIBITS A VERY POTENT PROGESTAGENIC EFFECT IN THE ENDOMETRIUM, AND CAUSES ENDOMETRIAL ATROPHY AFTER PROLONGED USE . IT ALSO MEDIATES AN ANTIANDROGENIC EFFECT THAT IS EQUIVALENT TO APPROXIMATELY ONE THIRD THAT OF CYPROTERONE ACETATE . A DOSE OF 2 MG INHIBITS THE GROWTH OF OVARIAN FOLLICLES AT 10 MM AND MAINTAINS THE CONCENTRATION OF PROGESTERONE AT A LOW LEVEL, BUT HAS A WEAK INHIBITORY EFFECT ON FSH AND LH. 1MG/KG OF DIENOGEST ALSO DIRECTLY INHIBITS OVULATION . IN CLINICAL TRIALS COMPOSING OF PATIENTS WITH ENDOMETRIOSIS, DIENOGEST THERAPY EFFECTIVELY REDUCED PAINFUL SYMPTOMS AND ENDOMETRIOTIC LESIONS ASSOCIATED WITH THE DISORDER . DIENOGEST DISPLAYS NO ANTIESTROGENIC ACTIVITY AS IT ACTIVATE NEITHER ESTROGEN RECEPTOR (ER) ? NOR ER? [A16570], AND CAUSES HYPOESTROGENIC EFFECTS INSTEAD AS IT IS SHOWN TO DECREASE THE RELATIVE EXPRESSIONS OF ER? AND ER? . IT HAS NO GLUCOCORTICOID OR MINERALOCORTICOID EFFECTS. IN COMBINED ORAL CONTRACEPTIVE PILLS (COCP) WITH ETHINYLOESTRADIOL, DIENOGEST CONJUCTION THERAPY EFFECTIVELY REDUCES THE SYMPTOMS OF ACNE AND HIRSUTISM, AS WELL AS IMPROVING EXCESSIVELY HEAVY OR PROLONGED MENSTRUAL BLEEDING .
MECHANISM OF ACTION
DIENOGEST ACTS AS AN AGONIST AT THE PROGESTERONE RECEPTOR (PR) WITH WEAK AFFINITY THAT IS COMPARABLE TO THAT OF PROGESTERONE BUT HAS A VERY POTENT PROGESTAGENIC EFFECT IN THE ENDOMETRIUM, CAUSING ENDOMETRIAL ATROPHY AFTER PROLONGED USE . IT PROMOTES ANTIPROLIFERATIVE, IMMUNOLOGIC AND ANTIANGIOGENIC EFFECTS ON ENDOMETRIAL TISSUE. DIENOGEST REDUCES THE LEVEL OF ENDOGENOUS PRODUCTION OF OESTRADIOL AND THEREBY SUPPRESSING THE TROPHIC EFFECTS OF OESTRADIOL ON BOTH THE EUTOPIC AND ECTOPIC ENDOMETRIUM . CONTINOUS ADMINISTRATION OF DIENOGEST RESULTS IN HYPERPROGESTOGENIC AND MODERATELY HYPOESTROGENIC ENDOCRINE ENVIRONMENT, WHICH CAUSES INITIAL DECIDUALIZATION OF ENDOMETRIAL TISSUE . IT IS AN ANTAGONIST AT ANDROGEN RECEPTORS, IMPROVE ANDROGENIC SYMPTOMS SUCH AS ACNE AND HIRSUTISM [A16570].
ABSORPTION
DIENOGEST IS RAPIDLY ABSORBED FOLLOWING ORAL ADMINISTRATION, WITH 91% BIOAVAILABILITY. THE PEAK PLASMA CONCENTRATION OF 47 NG/ML IS REACHED AT ABOUT 1.5 HOURS AFTER SINGLE INGESTION OF 2 MG . THE STABLE CONCENTRATIONS OF THE DRUG ARE REACHED AFTER TWO DAYS OF INITIAL TREATMENT .
VOLUME OF DISTRIBUTION
THE APPARENT VOLUME OF DISTRIBUTION (VD/F) OF DIENOGEST IS 40 L .
PROTEIN BINDING
DIENOGEST IS 90% NONOSPECIFICALLY BOUND TO ALBUMIN. IT DISPLAYS NO BINDING TO SEX HORMONE BINDING GLOBULIN (SHBG) OR CORTICOID BINDING GLOBULIN (CBG) .
METABOLISM
DIENOGEST UNDERGOES COMPLETE METABOLISM THAT IS MAINLY MEDIATED BY CYP3A4. THE METABOLITES ARE PHARMACOLOGICALLY INACTIVE AND RAPIDLY ELIMINATED FROM THE PLASMA.
ROUTE OF ELIMINATION
THE RATIO OF RENAL ELIMINATION TO FECAL ELIMINATION OF DIENOGEST IS 3:1, WHERE DIENOGEST IS PREDOMINANTLY EXCRETED IN THE FORM OF INACTIVE METABOLITES. MOST OF ORALLY ADMINISTERED DRUG IS EXCRETED IN THE URINE WITHIN THE FIRST 24 HOURS OF INGESTION .
HALF LIFE
ELIMINATION HALF-LIFE OF DIENOGEST IS AROUND 9-10 HOURS. THE HALF-LIFE OF URINARY METABOLITES EXCRETION IS 14 HOURS .
CLEARANCE
THE METABOLIC CLEARANCE RATE FROM SERUM (CL/F) IS 64 ML/MIN .
TOXICITY
ORAL LD50 IN MOUSE IS 4 MG/KG MSDS . IN A LONG-TERM CARCINOGENICITY STUDY INVOLVING RATS AND MICE, EXPOSURE OF 10 TIMES THE DOSE OF MAXIMUM RECOMMENDED CLINICAL DOSE OF DIENOGEST RESULTED IN INCREASED INCIDENCES OF PITUITARY ADENOMAS, FIBROEPITHELIAL MAMMARY TUMOURS, STROMAL POLYPS OF THE UTERUS AND MALIGNANT LYMPHOMA . THESE TUMORS ARE THOUGHT TO ARISE FROM MARKED SPECIES DIFFERENCES IN THE OPTIMAL OESTROGEN:PROGESTOGEN RATIO FOR REPRODUCTIVE FUNCTION. IN RAT LIVER FOCI ASSAY, DIENOGEST DID NOT INDUCE TUMOR PROMOTION ACTIVITY . DIENOGEST DOES NOT DISPLAY GENOTOXIC POTENTIAL.
(R)-WARFARIN DIENOGEST MAY DECREASE THE ANTICOAGULANT ACTIVITIES OF (R)-WARFARIN.
(S)-WARFARIN DIENOGEST MAY DECREASE THE ANTICOAGULANT ACTIVITIES OF (S)-WARFARIN.
2,4-THIAZOLIDINEDIONE THE THERAPEUTIC EFFICACY OF 2,4-THIAZOLIDINEDIONE CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
4-HYDROXYCOUMARIN THE THERAPEUTIC EFFICACY OF 4-HYDROXYCOUMARIN CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
4-OXORETINOL THE THERAPEUTIC EFFICACY OF DIENOGEST CAN BE DECREASED WHEN USED IN COMBINATION WITH 4-OXORETINOL.
7-NITROINDAZOLE THE METABOLISM OF DIENOGEST CAN BE INCREASED WHEN COMBINED WITH 7-NITROINDAZOLE.
ABACAVIR ABACAVIR MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ABCIXIMAB DIENOGEST MAY DECREASE THE ANTICOAGULANT ACTIVITIES OF ABCIXIMAB.
ACARBOSE THE THERAPEUTIC EFFICACY OF ACARBOSE CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
ACECLOFENAC ACECLOFENAC MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ACEMETACIN ACEMETACIN MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ACENOCOUMAROL THE THERAPEUTIC EFFICACY OF ACENOCOUMAROL CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
ACETAMINOPHEN THE METABOLISM OF DIENOGEST CAN BE INCREASED WHEN COMBINED WITH ACETAMINOPHEN.
ACETAZOLAMIDE THE METABOLISM OF DIENOGEST CAN BE INCREASED WHEN COMBINED WITH ACETAZOLAMIDE.
ACETOHEXAMIDE THE THERAPEUTIC EFFICACY OF ACETOHEXAMIDE CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
ACETYLSALICYLIC ACID DIENOGEST MAY DECREASE THE ANTICOAGULANT ACTIVITIES OF ACETYLSALICYLIC ACID.
ACITRETIN THE THERAPEUTIC EFFICACY OF DIENOGEST CAN BE DECREASED WHEN USED IN COMBINATION WITH ACITRETIN.
ACLIDINIUM ACLIDINIUM MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ACRIVASTINE DIENOGEST MAY DECREASE THE EXCRETION RATE OF ACRIVASTINE WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ACYCLOVIR ACYCLOVIR MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ADEFOVIR ADEFOVIR MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ADEFOVIR DIPIVOXIL ADEFOVIR DIPIVOXIL MAY DECREASE THE EXCRETION RATE OF DIENOGEST WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
AICA RIBONUCLEOTIDE THE THERAPEUTIC EFFICACY OF AICA RIBONUCLEOTIDE CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
ALBIGLUTIDE THE THERAPEUTIC EFFICACY OF ALBIGLUTIDE CAN BE DECREASED WHEN USED IN COMBINATION WITH DIENOGEST.
ALBUTREPENONACOG ALFA DIENOGEST MAY DECREASE THE EXCRETION RATE OF ALBUTREPENONACOG ALFA WHICH COULD RESULT IN A HIGHER SERUM LEVEL.
ADDITIONAL DATA AVAILABLE
路 EXTENDED DESCRIPTION
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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路 SEVERITY
Severity
A severity rating for each drug interaction, from minor to major.
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路 EVIDENCE LEVEL
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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路 ACTION
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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FOOD INTERACTIONS
路 AVOID GRAPEFRUIT PRODUCTS. GRAPEFRUIT INHIBITS THE CYP3A METABOLISM OF DIENOGEST, WHICH MAY INCREASE ITS SERUM CONCENTRATION.
路 AVOID ST. JOHN'S WORT. THIS HERB INDUCES THE CYP3A METABOLISM OF DIENOGEST AND MAY REDUCE ITS SERUM CONCENTRATION.
路 TAKE AT THE SAME TIME EVERY DAY.
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