Norgestrel/ Ethinyloestradiol

Registered South African indications:

• Contraception

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Previous or active thromboembolic disorders or those with a high risk of arterial or venous thrombotic diseases:
  • Patients who smoke and are over the age of 35 years
  • A history of, or current deep vein thrombosis (DVT), pulmonary embolism, or inherited thrombophilia
  • Patients with inherited or acquired hypercoagulopathies
  • Patients with cerebrovascular insufficiency or cerebrovascular disease
  • Patients with coronary artery disease. Norgestrel/ethinyloestradiol should be discontinued immediately if there is an onset of unexplained chest pain
  • Thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
  • Uncontrolled hypertension
  • Diabetes mellitus with vascular disease
  • Headaches with focal neurological symptoms or patients who have migraine headaches with an aura. Norgestrel/ethinyloestradiol should be discontinued immediately if migraine becomes focal, or if there is a loss of vision
  • Patients over the age of 35 with any migraine headaches
• Liver tumours (benign or malignant), liver disease, recurrent cholestatic jaundice
• Markedly impaired liver function
• History of or current hormone-dependent (estrogen or progestin-sensitive) neoplasms, or carcinoma of the breast
• Undiagnosed, abnormal vaginal bleeding
• Concomitant administration of hepatitis C medicine combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir, due to the potential for ALT elevations
• Depression not well controlled with treatment
• A history of depression with the use of hormonal contraceptives
• Patients known with inherited genetic mutations: BRCA 1 and BRCA 2 genes
• Early menstrual periods (before the age of 12 years)
• History of non-cancerous breast diseases (atypical hyperplasia or lobular carcinoma in situ)
• Previous treatment using radiation therapy to the chest or breast
• Previous exposure to diethylstilbestrol (DES)
• Pregnancy
• Lactation

Cautions

• Renal impairment
• Hypercholesterolaemia
• Familial hyperlipoproteinaemia
• Vaginal bleeding irregularities
• Cardiovascular disease
• Depression
• Chloasma
• Gallbladder disease
• Smokers
• Patients older than 40 years
• Periods of immobilisation
• Obesity

Forms avail. in SA and covered in this monograph: tab

Contraception

Norgestrel/ Ethinyloestradiol
500/50 (μg)

• Oral (tab): 1 tab, daily immediately after the evening meal or at bedtime, as nearly as possible at the same time each day for 21 days

THEN

Inactive tablets

• Oral (tab): 1 tab, dly for 7 days

Initiate 500μg norgestrel/50μg ethinyloestradiol tablet on day 1 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

Not indicated for use in premenarchal children

Contraindicated in early menstrual periods (before the age of 12 years)

Pregnancy

• Contraindicated
• Norgestrel/ oestrogen is contraindicated during pregnancy. Discontinue use of combination hormonal contraceptives (COCs) if pregnancy occurs. COCs use unintentionally, during early pregnancy has not been linked with  maternal or foetal adverse effects

Breastfeeding

• Contraindicated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated 

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Norgestrel : Probably porphyrinogenic (PRP)
• Oestrogen : Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Mood changes
• Cerebral haemorrhage
• Depression
• Dizziness
• Headache
• Migraine
• Nervousness

Cardiovascular Disorders 

• Coronary thrombosis
• Cerebrovascular accidents
• Myocardial infarction
• Venous thrombosis  
• Hypertension  
• Budd-Chiari syndrome
• Cerebral thrombosis
• Cerebrovascular accident
• Oedema
• Local thrombophlebitis
• Mesenteric thrombosis
• Pulmonary thromboembolism
• Retinal thrombosis

Gastrointestinal Disorders

• Gastrointestinal irritation
• Abdominal cramps
• Bloating
• Cholestasis
• Colitis
• Nausea and vomiting

Hepatobiliary Disorders

• Gall bladder disease
• Jaundice
• Benign hepatic tumours
• Cholestatic jaundice
• Hepatic adenoma
• Hepatic neoplasm (benign)

Genitourinary Disorders

• Amenorrhoea  
• Vaginal candidiasis
• Change in libido
• Breakthrough bleeding
• Breast hypertrophy
• Breast secretion
• Breast tenderness
• Change in cervical ectropion  
• Change in cervical secretions
• Cystitis-like syndrome
• Decreased lactation (postpartum)
• Spotting
• Transient infertility
• Vaginitis  
• Renal insufficiency

Endocrine and Metabolic Disorders

• Weight gain
• Decreased glucose tolerance
• Decreased serum folate level
• Hirsutism
• Increased serum triglycerides
• Increased sex hormone binding globulin
• Increased thyroxine binding globulin

Skin and Subcutaneous Tissue Disorders

• Skin pigmentation
• Acne vulgaris
• Allergic skin rash
• Chloasma
• Erythema multiform
• Erythema nodosum
• Loss of scalp hair
• Fluid retention  

Immune, Blood and Lymphatic System Disorders

• Decreased antithrombin III plasma level
• Hemolytic-uremic syndrome
• Hemorrhagic eruption
• Increased clotting factors VII, VII, IX, X
• Increased norepinephrine-induced platelet aggregation
• Prolonged prothrombin time

Sensory Disorders

• Ocular lesions
• Cataract
• Change in corneal curvature (steepening)
• Contact lens intolerance
• Optic neuritis

• Hepatitis C medicine combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir
• Antibiotic therapy
• Antiepileptic agents 
• Rifampicin
• Phenylbutazone

• Blood pressure

Specific cases may require

• Weight ₆
• Mental status
• Blood glucose level
• Lipid profile

Norgestrel and ethanol estradiol combination contraceptive acts by suppressing of gonadotropins, inhibiting ovulation and causing changes in the cervical mucus (which increases the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

COMBINATION PREPARATION

High-dose monophasic preparations

Norgestrel/ Ethinyloestradiol

Tablet 500μg/50μg

• Famynor (Mylan)
• Ovral (Pharmacare) originator