Activelle Side Effects

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Answer the side-effect intent for activelle without diagnosing; distinguish common from serious reactions and give safe next-step/reporting guidance.

What is Activelle?

Activelle contains the active ingredient Estradiol.

• Active ingredient — Estradiol
• Registration number — Z/21.8.1/339
• Registration holder — Adcock Ingram Limited

It is approved for:

• EVOREL patches contain a synthetic estrogen called estradiol
• It belongs to a group of medicines called hormone replacement therapy (HRT)
• The patches come in 4 different sizes: EVOREL 25, EVOREL 50, EVOREL 75, and EVOREL 100
• What EVOREL is used for EVOREL patches are used for hormone replacement therapy (HRT) in the treatment of symptoms of the menopause

Common side effects of Activelle

Not everyone gets side effects. The effects below are those listed in the South African approved leaflet, grouped using the leaflet’s own frequency wording.

Frequent side effects

• Genital yeast infections
• Allergic reactions
• Headache
• Dizziness
• Abnormal heart beat
• Excess amount of gas in stomach Loose watery stools
• Itching
• Rash
• Muscle pain
• Joint pain
• Breast pain
• Breakthrough bleeding or spotting
• Painful menstruation
• Pain
• Swelling (whole body or legs)
• Increased weight
• Feeling sick
• Abdominal pain
• Application site rash
• Application site itching
• Application site redness
• Application site reaction
• Application site swelling

Less frequent side effects

• Breast cancer
• Epilepsy
• Blood clots in veins
• Cancer of womb lining
• Depressed mood
• Suicidal thoughts/behavior and suicide
• Stroke, migraine
• Heart attack
• Clots in the deep veins, especially of lower leg
• Blood clot in the lungs
• Bloating of the stomach
• Gall stones
• Swelling below surface of skin
• Breast enlargement If you react to the patch itself with skin rashes or irritation, remove the patch and ask your doctor for advice

Serious side effects and warning signs

This leaflet does not set out a separate list of serious side effects. The general warning signs below apply to any medicine.

General warning signs that apply to any medicine

How long can side effects last?

How long a side effect lasts depends on the effect, the product, how long it has been used, and the person. Some effects ease within days as the body adjusts. Others continue for as long as the product is used. A few can persist after stopping, and some need review rather than waiting.

• Settling effects — mild effects that ease over the first days or weeks of use
• Ongoing effects — effects that continue while the product is being used and improve after stopping
• Persistent effects — effects that continue after stopping and need medical review
• Delayed effects — effects that appear after weeks or months rather than immediately

Which of these applies to a particular effect is a clinical question. If a side effect is not settling, is getting worse, or is affecting your daily life, that is worth a conversation with a pharmacist or doctor regardless of how long it has been going on.

Factors that may affect side effects

The approved leaflet identifies the following cautions and factors.

Do not use it at all if

• You are allergic (hypersensitive) to any of the ingredients in EVOREL patches
• You had, have or suspect that you have breast cancer
• You have a family history of breast cancer
• You have or suspect other cancers known to be sensitive to estrogens (e.g. endometrial cancer) or pre-malignant tumours (e.g. untreated atypical endometrial hyperplasia)
• You have undiagnosed genital bleeding
• You are pregnant or breast feeding
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to return to normal
• You have or have had blood clots (thrombosis) or inflammation of veins (thrombophlebitis) or alternatively, a family history thereof
• You have a previous or current venous thromboembolism (blood clots of deep veins in legs, clots in the lungs)
• You have active or recent past arterial thromboembolic disease (e.g. stroke, heart attack)
• Porphyria
• You have depression, which is not well controlled with treatment
• You have had depression with previous use of estrogen containing medicines

Use with care, and tell your doctor, if

• It is important that you have full and thorough physical and gynaecological examination and that your own family’s medical histories regarding thrombosis (blood clots) are taken before you start any Hormone Replacement Therapy (HRT)
• Repeated breakthrough bleeding, unexpected vaginal bleeding and changes noticed during breast examination require further evaluation
• You should receive regular full medical examinations whilst using EVOREL. Take special care with EVOREL. Before you use EVOREL, tell you doctor if:
• You are known to have inherited genetic changes called “BRCA1 and/or BRCA2 genes”
• You started your menstrual periods 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 diethylstilboestrol (DES)
• You are on treatment for depression
• You have had depression with previous use of estrogen and/or progesterone/progestogen containing medicines
• You have a substance abuse problem
• You have 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. If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, you should be closely supervised by your doctor as these conditions may recur or be aggravated during treatment with EVOREL, in particular:
• Leiomyoma (womb fibroids) or endometriosis
• Risk factors for blood clotting
• Risk factors for estrogen dependent tumours, e.g. first degree relative with breast cancer
• High blood pressure
• Liver disorders (including benign tumours of liver cells)
• Diabetes mellitus
• Gall stones
• Migraine or severe headache
• Systemic lupus erythematosus (lupus)
• A history of endometrial overgrowth (endometriosis)
• Epilepsy
• Breast tissue disease. Conditions which require monitoring by your doctor while on estrogen therapy:
• EVOREL may cause fluid retention. Heart or kidney abnormalities should be carefully observed
• Disturbances of liver function
• History of yellowing of the skin and or mucous membranes (jaundice)
• Pre-existing elevated blood fats, including triglycerides. Therapy should be discontinued in case a contraindication is discovered and in the following situations:
• Yellowing of skin (jaundice) or deterioration in liver function
• Increase in blood pressure
• New onset of migraine-type headache
• Pregnancy
• Epilepsy. EVOREL and breast cancer Breast cancer has been diagnosed slightly more often in women who use the Pill than in women of the same age who do not use the Pill. This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the 10 years after stopping use of the Pill. When you are using EVOREL, you must perform monthly breast self-examinations. Your doctor will advise you on when to report for breast examinations and any appropriate investigations. There is some evidence that HRT, such as EVOREL increases the risk of breast cancer in postmenopausal women receiving long-term HRT. You should discuss with your doctor for how long you should receive EVOREL treatment. If you have taken EVOREL for 5 years you should discuss with your doctor whether you should receive further HRT treatment. EVOREL and endometrial (womb) / ovarian cancer If you still have a womb (i.e. have not had a hysterectomy), taking EVOREL may increase the risk of overgrowth and cancer of the womb lining. You should discuss this with your doctor who could prescribe another hormone, progestogen, to take with the EVOREL since EVOREL in combination with a progestogen (for at least 12-14 days per cycle in non-hysterectomised women) reduces the risk. Long term use of estrogen-only HRT products such as EVOREL has been associated with an increased risk of ovarian cancer. EVOREL and heart disease / stroke / blood clots EVOREL does not protect against heart disease. Estrogen-only therapy such as EVOREL is associated with an increase in the risk of stroke. If you have had a blood clot in the leg or lung, a stroke or a heart attack or are immobile for any reason, such as after an operation, your doctor should decide on this and check you regularly if you do use it. If, while using EVOREL, you develop symptoms of a blood clot such as unexplained pains in the chest, abdomen or legs, the patch should be removed and your doctor should be contacted immediately. Depressed mood, depression and the risk of suicidality Estrogen containing medicines including EVOREL, may cause mood changes and depression, which may be severe. Severe depression is associated with a higher risk of suicidal thoughts/behavior (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. If you experience mood changes and depression contact your doctor for advice. Dementia There is some evidence of increased risk of deterioration of mental function (dementia) in women who start using continuous combined or estrogen-only HRT such as EVOREL. EVOREL should not be used for contraception. Children and adolescents EVOREL should not be used by children

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other health care provider for advice before using EVOREL
• You should not use EVOREL during pregnancy
• You should not breastfeed when using EVOREL
• If you fall pregnant whilst using EVOREL, stop treatment immediately and tell your doctor

Interactions and medicines to check

The approved leaflet names these interactions.

• Always tell your health care provider if you are taking any other medicine
• (This includes all complementary or traditional medicines.) Some medicines can alter the way EVOREL works, such as barbiturates, hydantoins, carbamazepine, meprobamate, phenylbutazone, rifampicin, rifabutin, bosentan, St
• John’s wort preparations (Hypericum perforatum) and certain non-nucleoside reverse transcriptase inhibitors, such as nevirapine and efavirenz, used in the treatment of HIV/AIDS
• Ritonavir and nelfinavir, used in the treatment of HIV/AIDS, may increase the metabolism of EVOREL and reduce plasma concentrations of estrogen
• Use of EVOREL with ritonavir and nelfinavir may result in a decrease in the effects and in unscheduled bleeding
• EVOREL may interfere with the plasma concentration of the anti-epileptic medicine lamotrigine
• This may have an effect on the control of your seizures
• If you have epilepsy and are taking medicines for this condition, inform your doctor as the dosage of your anti-epileptic medicine may need to be adjusted

What to do if you experience side effects

If you think you are having a side effect, the response depends on how severe it is. Use the warning signs above first — if any of those apply, treat it as urgent.

If the symptom is severe or frightening

Get medical help immediately. Call 10177 for an ambulance, or 112 from a mobile phone, or go to the nearest emergency department. Take the product and its packaging with you if you can.

If the symptom is mild but bothering you

• Write down what the symptom is, when it started, and how it relates to when you take the product
• Check the leaflet that came with the product to see whether the symptom is listed
• Speak to your pharmacist — for many questions this is the fastest route to a useful answer
• Contact the prescriber if the symptom is affecting your daily life or is not settling

You can also report a suspected side effect in South Africa. Reporting does not replace getting medical advice, and you do not need to be certain the product was the cause.

When to seek urgent medical help

Some symptoms need medical attention straight away rather than an appointment in a few days. Do not wait to see whether they settle.

Get same-day medical advice if you have

• A high fever, or a rash together with feeling generally unwell
• Yellowing of the eyes or skin, or unusually dark urine
• Unusual bruising or bleeding that you cannot explain
• Severe or persistent vomiting or diarrhoea, especially if you cannot keep fluids down
• A sudden change in mood, or thoughts of harming yourself
• Any symptom that is rapidly getting worse

How to report a suspected side effect in South Africa

South Africa has an official system for reporting suspected side effects, run by the South African Health Products Regulatory Authority (SAHPRA). Reports from the public and from healthcare professionals are how safety signals get detected after a product is already in use.

Who can report

Anyone can report — you do not have to be a healthcare professional, and you do not need to prove that the product caused the problem. A suspicion is enough. Patients, caregivers and family members can all submit a report.

What to have ready

• The name of the product, its strength and form, and the batch number if you have it
• Why it was being used, and when it was started and stopped
• What the suspected reaction was, when it began, and how long it lasted
• Any other medicines, supplements or remedies being used at the same time
• Basic details about the person affected — age and sex are usually enough

How to report

SAHPRA accepts adverse reaction reports through its e-Services reporting system and through the Med Safety mobile app. Healthcare professionals can also report through the same routes. Current forms and access points are published on the SAHPRA site.

• SAHPRA Health Products Vigilance — the main vigilance and reporting hub
• SAHPRA e-Services — current adverse reaction reporting access

For a fuller walkthrough see how to report an adverse drug reaction.

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