Ethinylestradiol + Gestodene

Oral
Oral contraception

Severe: Contraindicated.

May be taken with or without food.

Current or history of venous thromboembolism (VTE) (e.g. pulmonary embolism, DVT), known hereditary or acquired predisposition for VTE (e.g. APC-resistance, antithrombin-III deficiency, protein C or S deficiency), presence of multiple risk factors for VTE, conditions requiring prolonged immobilisation (e.g. major surgery); current or history of arterial thromboembolism (ATE) (e.g. stroke, MI) or prodromal conditions (e.g. angina pectoris, TIA), known hereditary or acquired predisposition to ATE (e.g. hyperhomocysteinaemia, anti-phospholipid antibodies), history of headache/migraine with focal neurological symptoms (e.g. aura), presence of multiple risk factors for ATE (e.g. severe hypertension, diabetes mellitus with vascular symptoms); current or history of pancreatitis associated with severe hypertriglyceridaemia, undiagnosed abnormal genital bleeding, breast or other estrogen-dependent neoplasms, current or history of hepatic adenoma or carcinoma. Severe hepatic impairment. Pregnancy. Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir (with or without ribavirin).

Patient with Crohn’s disease or ulcerative colitis, gallbladder disease, SLE, epilepsy, history of depression, hereditary angioedema, risk factors for CV disease (e.g. hypertension, dyslipidaemia), asthma. Obese patients, smokers (women >35 years). Renal and mild to moderate hepatic impairment. Lactation.

Significant: Chloasma, breakthrough bleeding, spotting, cholestasis, lipid changes, glucose intolerance, gallbladder disease, fluid retention, headache (e.g. migraine), optic neuritis, retinal vascular thrombosis.
Eye disorders: Intolerance to contact lenses.
Gastrointestinal disorders: Abdominal pain, nausea, vomiting.
Investigations: Increased or decreased weight.
Nervous system disorders: Dizziness, nervousness.
Psychiatric disorders: Altered or depressed mood.
Reproductive system and breast disorders: Amenorrhoea, dysmenorrhoea, breast tenderness, pain or enlargement; changes in libido, menstrual flow and cervical secretion or ectropion.
Potentially Fatal: VTE (e.g. DVT, pulmonary embolism), ATE (e.g. MI) or CV accident (e.g. stroke, TIA), hypertension, increased risk of breast, cervical, endometrial or ovarian cancer. Rarely, hepatic adenoma or carcinoma.

PO: X

Assess pregnancy status prior to therapy. Monitor weight, blood pressure during therapy; symptoms of VTE and ATE.

Symptoms: Nausea, vomiting, withdrawal bleeding. Management: Symptomatic treatment.

Ethinylestradiol: Reduced plasma concentration with hepatic enzyme-inducing drugs including antiretroviral agents (e.g. nevirapine), anticonvulsants (e.g. barbiturates, phenytoin), certain antibiotics (e.g. ampicillin, rifampicin) or antifungals (e.g. griseofulvin). Increased plasma concentrations with strong and moderate CYP3A4 inhibitors including azole antifungals (e.g. itraconazole), macrolide antibiotics (e.g. erythromycin); ascorbic acid, paracetamol, atorvastatin, etoricoxib. May increase the plasma concentrations of ciclosporin, theophylline, tizanidine. May decrease the plasma levels of lamotrigine.
Potentially Fatal: Concomitant use with the drugs containing ombitasvir/ paritaprevir/ritonavir and dasabuvir (with or without ribavirin) may increase the risk of ALT elevations.

Ethinylestradiol: Increased metabolism with St. John's wort.

May interfere with the measurement of sex hormone-binding globulin levels.

Description:
Mechanism of Action: Ethinylestradiol is a synthetic oestrogen while gestodene is a progestogen. Together, they inhibit ovulation by suppressing gonadotropin release. Other mechanisms such as changes in the cervical mucus (which increase the difficulty of sperm penetration into the uterus) and the endometrium (which reduce the likelihood of implantation) contribute to its contraceptive effect.
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract.
Ethinylestradiol: Bioavailability: Approx 45% (range: 20-65%). Time to peak plasma concentration: Approx 1-2 hours.
Gestodene: Bioavailability: 99%. Time to peak plasma concentration: Approx 1 hour.
Distribution: Enters breast milk (small amounts).
Ethinylestradiol: Volume of distribution: 2.8-8.6 L/kg. Plasma protein binding: >97%, mainly to albumin.
Gestodene: Volume of distribution: 0.7 L/kg. Plasma protein binding: 75-87% to sex hormone-binding globulin (SHBG); 13-24% to albumin.
Metabolism: Ethinylestradiol: Metabolised in the liver, initially via aromatic hydroxylation by the CYP3A4 isoenzyme, to form 2-hydroxyethinylestradiol and various conjugated metabolites which undergo enterohepatic recycling.
Gestodene: Metabolised in the liver via steroid metabolism pathways.
Excretion: Ethinylestradiol: Via urine and faeces (as metabolites) in a ratio of approx 4:6. Elimination half-life: 10-20 hours.
Gestodene: Via urine and faeces (as metabolites) in a ratio of approx 6:4. Elimination half-life: 12-15 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5991, Ethinylestradiol. https://pubchem.ncbi.nlm.nih.gov/compound/Ethinylestradiol. Accessed Apr. 27, 2022.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3033968, Gestodene. https://pubchem.ncbi.nlm.nih.gov/compound/Gestodene. Accessed Feb. 22, 2021.

Store below 25°C. Protect from light.

Oral Contraceptives

G03AA10 - gestodene and ethinylestradiol ; Belongs to the class of progestogens and estrogens in fixed combinations. Used as systemic contraceptives.

Aidulan 30/75 microgram Film-Coated Tablets (Lupin Europe Ltd). MHRA. https://products.mhra.gov.uk. Accessed 25/01/2021.

Anon. Ethinylestradiol [Ethinyl Estradiol] and Gestodene. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 25/01/2021.

Buckingham R (ed). Ethinylestradiol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 25/01/2021.

Buckingham R (ed). Gestodene. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 25/01/2021.

Femodene ED (Bayer PLC). MHRA. https://products.mhra.gov.uk/. Accessed 25/01/2021.

Joint Formulary Committee. Ethinylestradiol with Gestodene. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 25/01/2021.

Ministry of Health (Medsafe) Advice on the Use of Combined Oral Contraceptives. Medsafe. http://www.medsafe.govt.nz/. Accessed 25/01/2021.

Minulet (Pfizer). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 05/02/2021.