Trisequens ® Film-Coated Tablets

Trisequens ® is hormone replacement therapy (HRT) that is used:

• To relieve unpleasant symptoms of menopause like hot flushes, in postmenopausal women who still have their womb and with at least 6 months since their last natural period.
• As an adjunct therapy in prevention of osteoporosis (thinning of the bones), in postmenopausal women if they are at high risk of future fractures and are unable to take other medicines for this purpose.

Trisequens ® has no contraceptive effect. The experience of treating women older than 65 years is limited.

If any of the following applies to you. If you are not sure about any of the points below, talk to your doctor before taking Trisequens ®.

Do not take Trisequens ®:

• If you are pregnant or breastfeeding your baby.
• If you have, have had or suspect you have breast cancer, or you have a family history of breast cancer (mother, sister or grandmother).
• If you have, have had or suspect having any estrogen-dependent cancer, e.g. of the womb lining (endometrial cancer) or any other hormone dependent cancer.
• If you have or have ever had a liver disease and your liver function tests have not returned to normal.
• If you have or have ever had a blood clot in a vein (venous thromboembolism), such as in the legs (deep venous thrombosis) or the lungs (pulmonary embolism).
• If you have or previously have had a disease caused by blood clots in the arteries, such as a heart attack, stroke or angina.
• If you have any abnormal vaginal bleeding.
• If you have excessive thickening of the womb lining (endometrial hyperplasia) that is not being treated.
• If you have porphyria.
• If you have high blood pressure (hypertension).
• If you have a blood clotting disorder (such as protein C, protein S or antithrombin deficiency).
• If you are allergic (hypersensitive) to estradiol, norethisterone acetate or any other ingredients in Trisequens ® tablets (see section 6).
• If you have depression, which is not well controlled with treatment.
• If you have had depression with previous use of estrogen and/or progesterone/progestagen-containing medicines.

If any of the above conditions appear for the first time while taking Trisequens ®, stop taking it at once and consult your doctor immediately.

Before you use Trisequens ®, tell your doctor if:

• You are known to have inherited genetic changes called BRCA1 and/or BRCA2 genes.
• You started your menstrual periods early (before the age of 12 years).
• You have a history of non-cancerous breast diseases, such as atypical hyperplasia or lobular carcinoma in situ.
• You had any previous treatment using radiation therapy to the chest or breast.
• You have been treated or exposed while in your mother's womb to a medicine called diethylstilbestrol (DES).

Warnings and precautions

Take special care with Trisequens ®:

Tell your doctor if you have ever had of any of the following problems, before you start treatment with Trisequens ®, as these may return or become worse during treatment with Trisequens ®. If so, you should see your doctor more often for check-ups (at least once a year):

• Fibroids inside your womb.
• Growth of womb lining outside your womb (endometriosis) or a history of excessive growth of the womb lining (endometrial hyperplasia).
• Increased risk of getting an estrogen-sensitive cancer (such as having a mother, sister or grandmother who has had breast and/or endometrial cancer).
• A liver disorder, such as a benign liver tumour, or you have been diagnosed with a liver condition known as Dubin-Johnson syndrome or Rotor syndrome.
• Diabetes mellitus (high blood sugar) (with or without the involvement of blood vessels).
• Gallstones.
• Migraine or severe headaches.
• A disease of the immune system that affects many organs of the body (systemic lupus erythematosus, SLE).
• Epilepsy.
• Asthma.
• Heart failure.
• A disease affecting the eardrum and hearing (otosclerosis).
• High cholesterol (a very high level of fat in your blood (triglycerides)).
• Fluid retention due to cardiac or kidney problems.
• You are on treatment for depression.
• You have had depression with previous use of estrogen and/or progesterone/progestagen-containing medicines.
• You have a substance abuse problem.
• You have an underlying psychiatric disorder such as post-traumatic stress disorder or bipolar disorder.
• You have a family history of mental disorders.
• You have a history of physical or sexual abuse.

Estrogen and/or progesterone/progestagen containing medicines, including Trisequens ®, may cause mood changes and depression, which may be severe. Severe depression is associated with a higher risk of suicidal thoughts/behaviour (e.g., talking about suicide, withdrawing from social contact, having mood swings, being preoccupied with death or violence, feeling hopeless about a situation, increasing use of alcohol/drugs, doing self-destructive things, personality changes) and suicide.

Stop taking Trisequens ® and see a doctor immediately:

• If you notice any of the following when taking Trisequens ®:
• Any of the conditions mentioned in the “Do not take Trisequens ® section above.
• Yellowing of your skin or the whites of your eyes (jaundice), as these may be signs of a liver disease.
• A large rise in your blood pressure.
• Migraine-like headaches.
• If you become pregnant.
• If you experience mood changes and depression contact your doctor for advice.
• If you notice signs of a blood clot, such as:
• painful swelling and redness of the legs;
• sudden chest pain;
• difficulty in breathing.

Note: Trisequens ® is not a contraceptive. If it is less than 12 months since your last menstrual period or you are under 50 years old, you may still need to use additional contraception to prevent pregnancy. Speak to your doctor for advice.

Medical history and regular check-ups

The use of Trisequens ® carries risks which need to be considered when deciding whether to start taking it or whether to carry on taking it. Before you start taking Trisequens ®, your doctor will ask about your own and your family’s medical history. Your doctor may decide to examine your breasts and/or your abdomen and may do an internal examination. Once you’ve started on Trisequens ®, you should see your doctor for regular check-ups (at least once a year). At these check-ups, discuss the benefits and risks of continuing to take Trisequens ® with your doctor. Go for regular breast screening, as recommended by your doctor.

Do not share medicines prescribed for you with any other person. Always take Trisequens ® exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

If you are not switching from another hormone replacement therapy, you can start treatment with Trisequens ® on any convenient day. If you are switching from another hormone replacement therapy, ask your doctor when you should start treatment with Trisequens ®.

Take one tablet once a day, at about the same time each day. Each pack contains 28 tablets.

Days 1 – 12: Take one blue tablet every day for 12 days.
Days 13 – 22: Take one white tablet every day for 10 days.
Days 23 – 28: Take one red tablet every day for 6 days.

Take the tablets with a glass of water. The tablets can be taken with or without food and drink. Once you have finished the pack, start a new pack continuing the treatment without interruption. A menstruation-like bleeding usually occurs at the beginning of a new pack.

For further information on the use of the calendar-dial pack see “How to use the calendar dial pack” at the end of the package leaflet. Speak to your doctor if you think this dose is too strong or not strong enough. Talk to your doctor if you do not experience symptom relief after 3 months of treatment.

If you take more Trisequens ® than you should

If you have taken more Trisequens ® than you should, talk to a doctor or a pharmacist. An overdose of Trisequens ® could make you feel sick or vomit. In the event of overdosage, please consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre.

If you forget to take the/ missed a dose of Trisequens ®

Do not take a double dose to make up for a forgotten individual dose. If you forget to take a tablet one day, discard the tablet and continue treatment as before. Forgetting a dose may increase the likelihood of breakthrough bleeding and spotting.

If you stop taking Trisequens ®

If you would like to stop taking Trisequens ® talk to your doctor first, who will explain the effects of stopping treatment and discuss other possibilities with you. If you have any further questions on the use of Trisequens ®, ask your doctor or pharmacist.

Trisequens ® can have side effects. Not all side-effects reported for Trisequens ® are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking Trisequens ®, please consult your health care provider for advice.

If any of the following happens, stop taking Trisequens ® and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of your hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing; low blood pressure (paleness and coldness of skin, rapid heart beat), feeling dizzy, sweating;
• Rash, hives or itching;
• Fainting.

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to Trisequens ®. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Frequent side effects:

• Migraine, new or worse than before.

Less frequent side effects:

• Inflammation of a vein (superficial thrombophlebitis).
• Pulmonary embolism (blood clot).
• Inflammation of a deep vein associated with thrombosis (blood clot).

The following side effects have been reported but the frequency is not known:

• Heart attack and stroke.

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Frequent side effects:

• Breast pain or breast tenderness.
• Irregular periods or excessive bleeding during your periods.
• Headache.
• Weight gain.
• Vaginal inflammation.
• Vaginal infection with a fungus.
• Depression, new or worse than before.
• Nausea (feeling sick).
• Abdominal pain, swelling or discomfort.
• Enlargement or swelling of the breasts (breast oedema).
• Back pain.
• Leg cramps.
• Uterine fibroid (benign tumour), aggravation, occurrence or re-occurrence.
• Swelling of arms and legs (peripheral oedema).

Less frequent side effects:

• Bloating or flatulence.
• Acne.
• Hair loss.
• Male pattern hair growth.
• Hives (urticaria).
• Hyperplasia endometrial (excessive growth of the lining of the womb).
• Painful periods.
• Nervousness.
• Cancer of the lining of the womb (endometrial cancer).
• Increase in blood pressure or worsening of high blood pressure.
• Gall bladder disease, gall stones occurrence/recurrence or aggravated.
• Excessive secretion of sebum, skin eruption.
• Insomnia, dizziness, anxiety.
• Change in sexual desire.
• Visual disturbances.
• Decreased body weight.
• Vomiting (being sick).
• Heartburn.
• Vaginal and genital itching.

Other side effects of combined HRT:

The following side effects have also been reported after taking hormone replacement therapy.

• Various skin disorders:
• discolouration of the skin especially of the face or neck known as ‘pregnancy patches’ (chloasma).
• painful reddish skin nodules (erythema nodosum)
• rash with target-shaped reddening or sores (erythema multiforme).
• Probable dementia (brain disorder) in patients over the age of 65.
• Suicidal thoughts/behaviour and suicide.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: http://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of Trisequens ®.

Store at or below 25 °C. Do not refrigerate. Store all medicines out of reach of children. Do not use Trisequens ® after the expiry date which is stated on the label and carton. The expiry date refers to the last day of that month. Keep the container in the outer carton until required for use. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage system (e.g., toilets).