Kliofem

What is Kliofem?

Kliofem is a continuous combined hormone replacement therapy (HRT). It contains two synthetic hormones: estradiol (2 mg) and norethisterone acetate (1 mg). Estradiol is chemically identical to the primary oestrogen (estradiol-17β) naturally produced by a woman's ovaries. Norethisterone acetate is a progestogen, which mimics the effects of the body's own progesterone.

Mechanism of Action: A Simple Analogy

Think of your body's hormone system like a delicate thermostat. During menopause, the "oestrogen thermostat" drops significantly, causing symptoms like hot flushes (the body's "heating system" misfiring) and bone thinning (like the structural framework weakening). Kliofem provides a low, steady supply of oestrogen to gently top up the thermostat, alleviating symptoms and protecting bones. The progestogen component acts as a protective lining for the womb, counteracting the oestrogen's stimulating effect on the uterine lining to prevent abnormal overgrowth (hyperplasia) and cancer.

Biological Pathway: Estradiol binds to oestrogen receptors throughout the body (e.g., brain, skin, bones, blood vessels), modulating gene expression and cellular activity. This helps stabilise the body's temperature regulation, maintain skin and vaginal moisture, and slow bone resorption. Norethisterone acetate binds to progesterone receptors, primarily in the uterus, inducing a secretory change in the endometrium and preventing the unopposed oestrogen-induced proliferation.

What is Kliofem Used For?

Kliofem is licensed for two main purposes in postmenopausal women who have not had a hysterectomy:

1. Relief of Oestrogen-Deficiency Symptoms: Such as:
   • Vasomotor symptoms: Hot flushes, night sweats
   • Urogenital symptoms: Vaginal dryness, discomfort during intercourse
   • Other symptoms: Sleep disturbances, mood swings (where primarily related to menopause)

   It is prescribed only when symptoms significantly impair quality of life.

2. Prevention of Postmenopausal Osteoporosis: For women at increased risk of fractures, when other treatments are not suitable. The decision should be based on an individual risk assessment.

Target Patient Population

• Gender & Status: Postmenopausal women with an intact uterus.
• Time Since Menopause: At least 1 year since last natural menstrual period.
• Age: Primarily women aged 50-59 for symptom relief. Experience in women over 65 is limited, and HRT is generally not recommended for primary prevention of chronic diseases in this age group.
• Not for use in: Men, premenopausal women, or women with a history of hysterectomy.

Before Using Kliofem

Initiating HRT requires a thorough medical assessment as per the official Summary of Product Characteristics (SmPC):

Medical History Assessment Checklist

Your doctor will discuss your personal and family history of:

• Cancer: Breast, endometrial, ovarian, or other hormone-sensitive cancers.
• Thromboembolic Events: Deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, heart attack.
• Liver Disease: Past or present liver disorders, liver function tests.
• Vaginal Bleeding: Any unexplained bleeding.
• Other Conditions: Endometriosis, uterine fibroids, hypertension, migraine, diabetes, gallbladder disease, systemic lupus erythematosus (SLE), epilepsy, asthma, hypertriglyceridaemia, porphyria, angioedema.

Required Baseline Tests & Evaluations

• Physical Examination: Including blood pressure measurement.
• Breast Examination: Clinical breast exam; referral for mammography as per NHS screening programme or if clinically indicated.
• Pelvic Examination: If indicated by symptoms (e.g., unexplained bleeding).
• Other tests may be ordered based on individual history (e.g., liver function tests, lipid profile).

Kliofem Contraindications

Special Population Considerations

• Elderly (≥65 years): Limited experience. Increased absolute risk of stroke and VTE with age. HRT is not recommended for primary prevention of dementia or chronic disease in this group.
• Renal Impairment: No dosage adjustment needed, but use with caution in severe impairment due to potential fluid retention.
• Hepatic Impairment: Contraindicated in active liver disease or if liver function tests have not returned to normal. Hormones are metabolised in the liver.
• Pediatric/Adolescent: Not applicable. Kliofem is for postmenopausal women only.

Kliofem and Other Medicines

Some medicines can interact with Kliofem, reducing its effectiveness or increasing side effects. For detailed information, refer to the BNF entry for estradiol with norethisterone.

High-Risk Medication Combinations

• Liver Enzyme Inducers (can reduce HRT efficacy, cause breakthrough bleeding):
  • Antiepileptics: Phenobarbital, phenytoin, carbamazepine
  • Antibiotics: Rifampicin, rifabutin (for TB)
  • Antivirals: Nevirapine, efavirenz (HIV)
  • Herbal: St. John's Wort (Hypericum perforatum)
• Medicines whose effects may be altered by HRT:
  • Lamotrigine (epilepsy): HRT may decrease lamotrigine levels, potentially increasing seizure frequency.
  • Cyclosporine (immunosuppressant): Kliofem may increase cyclosporine levels (monitoring required).

Always inform your doctor and pharmacist about all medicines you take, including over-the-counter and herbal products.

Pregnancy & Breastfeeding

Kliofem is absolutely contraindicated during pregnancy and breastfeeding.

• Pregnancy: If you become pregnant, stop taking Kliofem immediately and contact your doctor. The hormones could harm the developing fetus.
• Breastfeeding: Do not use Kliofem while breastfeeding. Hormones can pass into breast milk.
• Contraception: Kliofem is NOT a contraceptive. Women under 50 or within 12 months of their last natural period may still be fertile and should use non-hormonal barrier contraception (e.g., condoms) if pregnancy prevention is required.

Driving & Machine Operation

Kliofem has no known effect on the ability to drive or operate machinery. However, if you experience side effects such as dizziness, migraine, or visual disturbances, you should refrain from these activities until you feel well again.

Kliofem Ingredients

Active Ingredients (per tablet)

• Estradiol 2 mg (as estradiol hemihydrate) – The primary therapeutic oestrogen.
• Norethisterone acetate 1 mg – A progestogen to protect the uterine lining.

Other Ingredients (Excipients)

• Lactose monohydrate – A sugar used as a filler/binder. Important for patients with lactose intolerance.
• Maize starch, hydroxypropylcellulose, talc, magnesium stearate – Used in the tablet core.
• Film-coating: Hypromellose, triacetin, talc – Gives the tablet its smooth, coated finish.

How to Use Kliofem

Kliofem is designed for continuous daily use, without a break.

Kliofem Dosage Guidelines

Standard Adult Dose: One white 2 mg/1 mg tablet taken orally once daily, every day.

Treatment Initiation: Start on any convenient day. If switching from a sequential (cyclical) HRT that causes monthly bleeding, start Kliofem the day after the last active tablet of your previous regimen, or immediately after the bleeding phase ends.

Duration: Use the lowest effective dose for the shortest duration necessary. Re-evaluate the need for HRT annually with your doctor.

Administration Instructions

For detailed instructions, see the NHS guide on how and when to take continuous combined HRT.

1. Timing: Take your tablet at roughly the same time each day (e.g., with breakfast). This helps maintain steady hormone levels.
2. How to take: Swallow the tablet whole with a glass of water. It can be taken with or without food.
3. Using the Calendar Pack:
   1. Set the day reminder: Turn the inner disc to align the current day of the week with the small plastic tab.
   2. Take the first tablet: Break the plastic tab and tip out the first tablet.
   3. Move the dial daily: Each day, after removing the tablet, turn the transparent dial clockwise by one space (as shown by the arrow) to reveal the next tablet.
4. After finishing a pack (28 tablets), start a new pack immediately the next day without a break.

Missed Dose Management

Note: A missed dose may increase the chance of breakthrough bleeding or spotting.

Overdose Information

Accidental ingestion of several tablets at once is unlikely to cause serious harm, but may intensify side effects.

• Oestrogen overdose symptoms: Nausea, vomiting, breast tenderness, abnormal vaginal bleeding.
• Progestogen overdose symptoms: Feeling depressed, tired, acne, increased facial/body hair.

Action: If you take too many tablets, contact your doctor, pharmacist, or call NHS 111 for advice. There is no specific antidote; treatment is supportive.

Kliofem Side Effects

Like all medicines, Kliofem can cause side effects. The following lists are based on the official Product Information.

Serious Side Effects – STOP taking Kliofem and seek IMMEDIATE medical help if you experience:

• Signs of a severe allergic reaction (anaphylaxis): Swelling of face/tongue/throat, difficulty breathing/swallowing, hives.
• Signs of a blood clot (venous thromboembolism): Sudden severe chest pain, breathlessness, coughing up blood; or painful swelling/redness in one leg.
• Signs of a stroke: Sudden weakness/numbness on one side, slurred speech, severe headache.
• Signs of liver problems: Yellowing of skin/eyes (jaundice), dark urine, severe upper abdominal pain.
• Unexplained vaginal bleeding that starts or persists after being on treatment.
• Migraine-like headaches for the first time.

Other Side Effects (by frequency)

Very Common (≥1 in 10): Breast pain/tenderness, vaginal bleeding (especially in first 3-6 months).

Common (≥1 in 100 to <1 in 10): Headache, migraine, nausea, abdominal pain, weight gain, fluid retention, vaginal thrush, depression, back pain, leg cramps, uterine fibroid growth.

Uncommon (≥1 in 1,000 to <1 in 100): Acne, hair loss, abnormal hair growth, bloating, allergic skin reactions, nervousness.

Rare (≥1 in 10,000 to <1 in 1,000): Venous thromboembolism (DVT/PE).

Very Rare (<1 in 10,000): Endometrial cancer, endometrial hyperplasia, gallbladder disease, heart attack, stroke, angioedema, visual disturbances.

Reporting Side Effects: You can report suspected side effects via the MHRA Yellow Card Scheme.

How to Store Kliofem

• Keep out of sight and reach of children.
• Store in the original outer carton to protect from light.
• Do not refrigerate.
• Do not use after the expiry date printed on the pack.
• Disposal: Do not throw away via wastewater or household waste. Return any unused tablets to your pharmacy for safe disposal.

Kliofem Pack Information

• Pack sizes marketed in the UK: Calendar packs containing 1 x 28 tablets or 3 x 28 tablets.
• Marketing Authorisation Holder: Novo Nordisk Limited, Gatwick, UK.
• Manufacturer: Novo Nordisk A/S, Denmark.
• PL Number: [To be inserted based on specific product]

Where Can I Buy Kliofem Online in the UK