Nomegestrol Acetate/ Estradiol Hemihydrate

Registered South African indications: 

• Contraception

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Presence or history of venous thrombosis (deep venous thrombosis, pulmonary embolism)
• Presence or history of arterial thrombosis (myocardial infarction, cerebrovascular accident) or prodromal conditions (e.g. transient ischaemic attack, angina pectoris)
• History of migraine with focal neurological symptoms
• Presence of severe or multiple risk factors for venous or arterial thrombosis such as:
  • Diabetes mellitus with vascular symptoms
  • Severe hypertension
  • Severe dyslipoproteinaemia
• Major surgery with prolonged immobilisation
• Hereditary or acquired predisposition for venous or arterial thrombosis, such as activated protein C resistance, antithrombin-lll deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia, and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)
• Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia
• Presence or history of severe hepatic disease as long as liver function values have not returned to normal
• Presence or history of liver tumours (benign or malignant)
• Known or suspected sex steroid-influenced malignancies (e.g., of the genital organs or the breasts)
• Known or suspected pregnancy

Cautions

• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Hypertriglyceridaemia, or a family history thereof
• Jaundice and/or pruritus related to cholestasis
• Gallstone formation
• Porphyria
• Systemic lupus erythematosus
• Haemolytic uraemic syndrome
• Sydenham's chorea
• Children
• Herpes gestationis
• Otosclerosis-related hearing loss
• Hereditary angioedema
• Diabetes mellitus
• Inflammatory bowel disease
• History of chloasma gravidarum
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption 

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

Contraception

Nomesestrol/ Oestradiol Hemihydrate
Tablet 2.5/1.5mg

• Oral (tab): 1 tab, dly; Treatment duration: 24 days

THEN

Inactive tablets

• Oral (tab): 1 tab, dly; Treatment duration: 4 days

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Take at same time everyday

Continue following pack without a break

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Withdrawal bleeding usually starts on day 2-3 after the last active tablet 

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See additional prescribing points

Not established for use in children below 18 years

Pregnancy

• Contraindicated

Breastfeeding

• Caution; not recommended
• Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the breast milk, but there is no evidence that this adversely affects infant health
• Breastfeeding may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should not be recommended until the breast-feeding mother has completely weaned her child and an alternative contraceptive method should be proposed to women wishing to breastfeed

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Mild to moderate: Caution; no information available 
• Severe: Contraindicated

Elderly

• Caution; no information available

Porphyria Information

• Probably porphyrinogenic (PRP) 

Drugs in Sport 

• Permitted - No warnings

Central Nervous System Disorders

• Headache 
• Migraine
• Cerebrovascular accident
• Transient ischaemic attack
• Disturbance in attention
• Decreased libido
• Depression
• Depressed mood
• Altered mood 
• Increased libido
• Irritability

Cardiovascular Disorders

• Hot flush
• Venous thromboembolism

Gastrointestinal Disorders

• Nausea
• Abdominal distension

Hepatobiliary Disorders

• Cholelithiasis
• Cholecystitis
• Increased hepatic enzyme 

Genitourinary Disorders

• Abnormal withdrawal bleeding
• Metorrhagia
• Menorrhagia
• Breast pain
• Pelvic pain
• Hypomenorrhoea
• Breast swelling
• Galactorrhoea
• Uterine spasm
• Premenstrual syndrome
• Breast mass
• Dyspareunia
• Vulvovaginal dryness
• Vaginal odour
• Vulvovaginal discomfort

Endocrine and Metabolic Disorders

• Increased appetite
• Fluid retention
• Decreased appetite
• Dry mouth
• Increased weight

Musculoskeletal Disorders

• Sensation of heaviness

Skin and Subcutaneous Tissue Disorders

• Hyperhydrosis
• Alopecia
• Pruritus
• Dry skin
• Seborrhea
• Chloasma
• Hypertrichosis
• Oedema

Sensory Disorders

• Contact lens intolerance
• Dry eye

• CYP450 inducers
• CYP3A4 inhibitors
• Lamotrigine 

• Blood pressure
• Pregnancy test

Administration directions

No preceding hormonal contraceptive use

• Start tablet on first day of menstrual cycle 
• No additional contraceptive measures are necessary
• If starting on days 2-5, a barrier method of contraception is required until the patient has completed 7 days of uninterrupted active tablets

Changing from a combined hormonal contraceptive, vaginal ring or transdermal patch

• Start on the day after the last active tablet of the previous combined oral contraceptive
• In the case of a vaginal ring or transdermal patch, start on the day of removal or when the next application would have been due

Changing from a progestogen-only method or from a hormone-medicated intrauterine system (IUS)

• May switch any day from the progestogen-only pill
• Treatment with Nomegestrol/ Oestradiol Hemihydrate can be started on the next day
• Nomegestrol/ Oestradiol Hemihydrate treatment can be started on the day of the implant or IUS removal
• Nomegestrol/ Oestradiol Hemihydrate therapy can be started on the day the next injection would have been due
• A barrier method of contraception is required until the patient has completed 7 days of uninterrupted active tablets

Following first trimester abortion

• Treatment with Nomegestrol/Oestradiol Hemihydrate may be started immediately
• No additional contraceptive method is required

Following delivery or second trimester abortion

• Start between day 21-28 after delivery or second trimester abortion
• A barrier method of contraception is required until the patient has completed 7 days of uninterrupted active tablets
• If intercourse has occurred within this 28 day period, pregnancy should be excluded or the patient should wait until her next menstrual period to start the therapy

Missed tablets

• If less than 12 hours since missing dose, the patient can take the tablet when she remembers it
• If more than 12 hours have elapsed after missing a tablet:

Active tablets

• During day 1-7: Take the last missed dose as soon as remembered, even if this means taking 2 tab at once. Continue to take tab as normal thereafter. An additional barrier contraceptive should be used for 7 days. If intercourse took place during the preceding 7 days the possibility of pregnancy should be considered
• During day 8-17: Take the last missed dose as soon as remembered, even if this means taking 2 tab at once. Continue to take tab as normal thereafter. Provided the tablets were taken correctly in the 7 days preceding, no additional contraceptive precautions need to be taken. However, if more than 1 tablet has been missed, use extra precautions until completed 7 days of uninterrupted active tablet-taking
• During day 18-24: Take the last missed dose as soon as remembered, even if this means taking 2 tab at once. Continue to take tab as normal thereafter, until the active tablets are used up. Discard the 4 placebo tablets from the last row and start the next blister pack immediately. Breakthrough bleeding or spotting may occur. No need for additional contraceptive measures provided the tablets were taken correctly in the 7 days preceding

OR

• Discontinue active tablet-taking from the current blister pack. Take placebo tablets from the last row for a maximum of 3 days such that the total number of placebo plus missed active tablets is not more than 4, and subsequently continue with the next blister pack
• If the woman missed tablets and subsequently has no withdrawal bleed in the placebo tablet phase, the possibility of a pregnancy should be considered

Placebo tablets

• Contraceptive protection is not reduced. Placebo tablets from the last row of the blister can be discarded, to avoid unintentionally prolonging the placebo tablet phase

Gastrointestinal disturbances

• If vomiting occurs within 3-4hrs after active tablet-taking, the tablet should be considered as missed and a new tablet should be taken as soon as possible. The new tablet should be taken within 24hrs of the usual time of tablet-taking if possible. The next tablet should then be taken at the usual time
• If 24 or more hours have passed since last tablet intake, the advice concerning missed tablets, as above, is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra active tablet(s) from another pack

Shifting or delaying a period

• Delaying a period: Continue with another blister pack without taking the placebo tablets from current pack. The extension can be carried on for as long as wished until the end of the active tablets in the second pack. Regular intake of is then resumed after the placebo tablets have been taken of the second pack. During the extension the woman may experience breakthrough bleeding or spotting
• To shift periods to another day of the week, shorten forthcoming placebo tablet phase with a maximum of 4 days. The shorter the interval, the higher the risk of no withdrawal bleed and may experience breakthrough bleeding and spotting during the subsequent pack

Nomegestrol acetate is a progestogen derived from, and structurally similar to, the naturally occurring steroid hormone, progesterone. Nomegestrol acetate has an affinity for the progesterone receptor and has anti-gonadotropic activity, moderate anti-androgenic activity, and is devoid of any oestrogenic, androgenic, glucocorticoid or mineralocorticoid activity. 17β-Estradiol, is a natural oestrogen identical to the endogenous human 17β-estradiol. During use of 2.5mg nomegestrol acetate and 1.5mg estradiol the average 17β-estradiol levels are comparable to the 17β-estradiol levels during the early follicular and late luteal phase of the menstrual cycle.

COMBINATION PREPARATIONS

Nomegestrol/ Oestradiol Hemihydrate

Tablet 2.5/1.5mg

• Zoely (MSD) originator