Dienogest/ Estradiol Valerate

Registered South African indications:

• Contraception

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hepatic impairment
• Porphyria
• Current or history of venous thromboembolism
• Thrombophilia
• Major surgery with prolonged immobilisation
• Current or history of arterial thromboembolism
• Cerebrovascular disease
• Migraine with focal neurological symptoms
• Current or history of liver tumours
• Diabetes mellitus with vascular symptoms
• Severe hypertension
• Severe dyslipoproteinaemia
• Known or suspected sex-steroid influenced malignancies
• Undiagnosed vaginal bleeding

Cautions

• Breastfeeding
• Renal impairment
• Obesity
• Family history of venous thromboembolism
• Cancer
• Systemic lupus erythematosus
• Haemolytic uraemic syndrome
• Chronic inflammatory bowel disease
• Sickle cell disease
• Age over 35 years
• Smoking
• Positive family history of arterial thromboembolism
• Diabetes mellitus
• Hyperhomocysteinaemia
• Valvular heart disease
• Atrial fibrillation
• Hypertriglyceridaemia
• Conditions known to worsen during pregnancy
• Hereditary angioedema
• Depression
• Epilepsy
• Cardiac dysfunction
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

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

Contraception

Estradiol valerate
3mg

• Oral (tab): 1 tablet, dly for 2 days

THEN

Dienogest /Estradiol valerate
2/2 (mg)

• Oral (tab): 1 tablet, dly for 5 days

THEN

Dienogest/ Estradiol valerate
2/3 (mg)

• Oral (tab): 1 tablet, dly for 17 days

THEN

Estradiol valerate
1mg

• Oral (tab): 1 tablet, dly for 2 days

THEN

Inactive tablets

• Oral (tab): 1 tablet, dly for 2 days

Initiate with estradiol valerate 3mg tablet on day 1 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

See additional prescribing points

Not established for use in children below 18 years

Pregnancy

• Not indicated during pregnancy
• Dienogest/ Oestrogen should not be used during pregnancy
• If pregnancy occurs during use of this medicine, further intake must be stopped. However, extensive epidemiological studies with ethinylestradiol containing COCs have revealed neither an increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during pregnancy. Animal studies do not indicate a risk for reproductive toxicity
• The increased risk of VTE during the postpartum period should be considered when re-starting dienogest/ oestrogen

Breastfeeding

• Caution; not recommended
• Lactation may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should generally not be recommended until the breastfeeding mother has completely weaned her child. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk. These amounts may affect the child

Fertility

• Dienogest is indicated for the prevention of pregnancy

Renal Impairment

• Caution; no dose adjustment recommend

Hepatic Impairment

• Contraindicated

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Emotional disorders
• Insomnia
• Decreased libido
• Increased libido
• Mood change
• Aggression
• Anxiety
• Dysphoria
• Nervousness
• Nightmare
• Restlessness
• Sleep disorder
• Headache
• Dizziness
• Migraine
• Disturbance in attention
• Paraesthesia
• Fatigue
• Irritability

Cardiovascular Disorders

• Myocardial infarction
• Palpitations
• Hot flushes
• Hypertension
• Bleeding varicose vein
• Venous thromboembolism
• Arterial thromboembolism
• Hypotension
• Phlebitis superficialis
• Vein pain
• Oedema
• Chest pain
• Blood pressure changes

Respiratory Disorders

• Asthma
• Dyspnoea
• Epistaxis

Gastrointestinal Disorders

• Oral herpes
• Abdominal pain
• Nausea and vomiting
• Constipation
• Diarrhoea
• Dry mouth
• Dyspepsia
• Gastroesophageal reflux disease

Hepatobiliary Disorders

• Increased liver enzymes
• Focal nodular hyperplasia of the liver
• Chronic cholecystitis

Genitourinary Disorders

• Vulvovaginal mycotic infection
• Vaginal infection
• Candidiasis
• Pelvic inflammatory disease
• Urinary tract infection
• Bacterial vaginitis
• Urinary tract pain
• Amenorrhea
• Dysmenorrhoea
• Intracyclic bleeding
• Cervical dysplasia
• Dysfunctional uterine bleeding
• Dyspareunia
• Menorrhagia
• Menstrual disorder
• Ovarian cyst
• Pelvic pain
• Premenstrual syndrome
• Uterine leiomyoma
• Uterine spasm
• Vaginal bleeding
• Vaginal discharge
• Vulvovaginal dryness
• Abnormal withdrawal bleeding
• Cervical polyp
• Cervix erythema
• Coital bleeding
• Genital discharge
• Hypomenorrhea
• Delayed menstruation
• Ruptured ovarian cyst
• Vaginal odour
• Vulvovaginal burning sensation
• Vulvovaginal discomfort
• Abnormal cervical smear

Endocrine and Metabolic Disorders

• Increased appetite
• Increased weight
• Decreased weight
• Fluid retention
• Hypertriglyceridaemia
• Breast discomfort
• Breast enlargement
• Breast mass
• Fibrocytic breast disease
• Benign breast neoplasm
• Breast carcinoma 
• Breast cyst
• Breast discharge
• Galactorrhoea

Musculoskeletal Disorders

• Muscle spasms
• Back pain
• Sensation of heaviness

Skin and Subcutaneous Tissue Disorders

• Tinea versicolor
• Acne
• Alopecia
• Hyperhidrosis
• Pruritus
• Rash
• Allergic skin reactions
• Chloasma
• Dermatitis
• Hirsutism
• Hypertrichosis
• Neurodermatitis
• Pigmentation disorder
• Seborrhoea

Immune, Blood and Lymphatic System Disorders

• Lymphadenopathy
• Pyrexia

Sensory Disorders

• Ocular histoplasmosis syndrome
• Vertigo
• Contact lens intolerance
• Dry eye
• Eye swelling

• CYP450 inducers
• CYP3A4 inhibitors
• HIV protease inhibitors
• Non-nucleoside reverse transcriptase inhibitors
• Ciclosporin
• Lamotrigine

• Physical examination
• Pregnancy test
• Blood pressure

Specific cases may require

• Mental status
• Blood glucose
• Lipid profile
• Hepatic function

Initiating in special circumstances

• First trimester abortion: Can be initiated immediately (no additional contraception required)
• Postpartum or second trimester abortion: Initiate on day 21-28 postpartum/post-abortion; If initiating later than 28 days, additional non-hormonal contraception required for 9 days

Special circumstances requiring additional contraception

• Vomiting 3-4hrs after taking active tablet: Take addition, corresponding tablet from another blister pack

Missed dose

• Single tablet forgotten and less than 12hrs late: Take missed tablet as soon as remembered and take further tablets at their usual time
• Single tablet forgotten and more than 12hrs late: Take missed tablet as soon as remembered and take further tablets at their usual time. No more than 2 tablets to be taken on a given day. Additional advise as below:

This estrogen-progestogen combination acts by inhibiting ovulation by suppression of the mid-cycle surge of luteinising hormone, the inspissation of cervical mucus so as to constitute a barrier to sperm and the rendering of the endometrium unreceptive to implantation. Dienogest is a nortestosterone derivative with antiandrogenic activity

COMBINATION PREAPARATIONS

Multiphase preparations

Estradiol valerate/ Estradiol valerate/ Estradiol valerate/ Dienogest/ Dienogest

Tablet 1mg/2mg/3mg/2mg/3mg

• Qlaira (Bayer) originator