SEQUIDOT transdermal patch estradiol/norethisterone acetate
What Is Sequidot, And What Sequidot Used For
Sequidot is a drug used for Hormone Replacement Therapy ( HRT ). Sequidot consists of two different patches – phase I (small rectangular patch with rounded corners) and phase II (round patches ) – which are attached to the skin at different times. It contains two female sex hormones; estrogen and progestogen. Sequidot is used for women whose menstruation has stopped ( menopause ) at least 6 months after their last natural menstruation.
Sequidot is used to:
Relieve symptoms during and after menopause
Sequidot is used to treat postmenopausal symptoms in women who have their uterus left. When menstruation ceases ( menopause ), a woman’s estrogen drops. It can cause problems such as
Sweating and hot flashes
- Sleep problems
- Irritability
- Dryness in the vagina
Sequidot relieves these symptoms after menopause. Sequidot should only be used if the problems cause problems in daily life.
Prevent osteoporosis
After menopause, some women suffer from osteoporosis. Discuss all possible options with your doctor.
If you have an increased risk of fractures (bone fractures) and other medicines that are not suitable for you, you can use Sequidot to prevent osteoporosis after menopause.
Estradiol or norethisterone acetate contained in Sequidot may also be approved for treating other conditions not mentioned in this product information. Ask your doctor, pharmacist, or another healthcare professional if you have further questions, and always follow their instructions.
What You Need To Know Before Using Sequidot
Medical background and regular check-ups
- The use of HRT involves risks that must be considered when deciding to start or continue an ongoing treatment.
- Experience is limited for treating women whose menstruation has stopped prematurely (when the ovaries have stopped working or the uterus has been operated on). If you belong to that group, HRT’s risks may differ. Talk to your doctor.
- Before starting treatment (or resuming treatment), your doctor will ask about your and your family’s medical background. Your doctor may do a general medical and gynecological examination, including an examination of your breasts.
- Once you have started treatment, you should go for regular medical check-ups at least once a year. During these check-ups, you should discuss with your doctor the benefits and risks of continued treatment.
- Perform regular examinations of the breasts according to the doctor’s recommendations.
- Do not use Sequidot
- If any of the following apply to you. If you are not sure, talk to your doctor before using Sequidot.
- Do not use Sequidot:
- If you have or have had breast cancer or there is a suspicion that you may have it.
- If you have or have had estrogen-dependent cancer, such as cancer of the uterine lining (endometrium), or if there is a suspicion of such cancer.
- If you have unexpected genital bleeding that a doctor has not investigated.
- If you have endometrial hyperplasia (severe thickening of the uterine lining) and are not being treated for it.
- If you have or have had a blood clot in a vein (venous thromboembolism ), in your legs (deep vein thrombosis ), or in your lungs ( pulmonary embolism ).
- If you have a coagulation disorder, a condition with an increased risk of blood clots (lack of protein C, protein S, or antithrombin). Suppose you have or have recently had a disease caused by a blood clot in the arteries, such as a heart attack, stroke, or angina.
- If you have or have had any liver disease and still have abnormal liver values
- If you have porphyria, a rare inherited blood disorder.
- If you are allergic to estradiol, norethisterone, or any of the other ingredients of this medicine (see section 6 Contents of the pack and other information).
If any of the above affects you the first time you use Sequidot, stop using Sequidot and contact your doctor immediately.
Warnings And Cautions
Talk to your doctor if you have or have had any of the following problems before starting treatment. They may recur or worsen during treatment with Sequidot. Should this occur, you should have more frequent check-ups with a doctor.
- If you have any disease affecting the lining of the uterus, as well as muscle knots ( fibroids ), endometriosis, or have had endometrial hyperplasia (severe thickening of the uterine lining)
- If you have an increased risk of getting a blood clot (see below “Blood clots in a vein ( thrombosis )”)
- If a close relative has had breast cancer or other estrogen-dependent cancer
- High blood pressure
- Liver disease e.g. liver adenoma (benign tumour)
- Diabetes
- Gallstone disease
- If you get a migraine or severe headache
- If you have systemic lupus erythematosus ( SLE ) – an autoimmune disease that affects many organs in the body
- Epilepsy
- Asthma
- Otosclerosis (ossification of the middle ear leading to a hearing loss)
- Hypertriglyceridemia (elevated blood lipids)
- Fluid retention due to heart or kidney disease
- A condition called hypothyroidism (your thyroid gland does not produce enough thyroid hormone), and you are taking thyroid hormone as a replacement therapy.
- Hereditary and acquired angioedema.
You should contact a doctor immediately and discontinue treatment if any of the following occur:
- Some of the things mentioned in the section ‘Do not use Sequidot’
- If the skin or whites of the eyes turn yellow (jaundice); it may be a symptom of liver disease
- Swelling of the face, tongue, or throat and difficulty swallowing or hives, together with difficulty breathing, may indicate angioedema
- If your blood pressure rises sharply (symptoms may include headache, fatigue, or dizziness)
- If you are experiencing migraine-like headaches for the first time
- If you become pregnant
- If you get symptoms of a blood clot, such as
- Painful swelling and redness of the legs
- Sudden chest pain
- For breathing difficulties and more information, see below “Blood clots in a vein ( thrombosis )”
Note: Sequidot is not a contraceptive. If it is less than 12 months since your last period, or if you are under 50, you may still need to use contraception to avoid pregnancy. Consult your doctor.
HRT and cancer
Severe thickening of the uterine lining ( endometrial hyperplasia ) and cancer of the uterine lining (endometrial cancer)
Using HRT with estrogen alone increases the risk of severe thickening of the uterine lining and cancer of the uterine lining.
The progestogen in Sequidot protects you against this additional risk. Adding a progestogen for at least 12 days in each 28-day cycle greatly reduces this risk. Therefore, a progestogen is included in each phase II patch.
For women with a uterus left, who do not take HRT, an average of 5 out of 1,000 women aged 50–65 will be diagnosed with endometrial cancer.
For women aged 50-65 who have the uterus left and who take HRT with estrogen alone, between 10 and 60 women out of 1,000 users will be diagnosed with endometrial cancer (i.e. between 5 and 55 extra cases), depending on the dose of one and how as long as it is taken.
Unexpected bleeding
You will have bleeding once a month (so-called dropout bleeding) when you use Sequidot. However, if you experience unexpected bleeding or splashing in addition to your monthly bleeding, and these:
- Lasts longer than 6 months
- Starts after using Sequidot for 6 months
- Continues after you have stopped using Sequidot
you should see a doctor as soon as possible.
- Breast cancer
- Data show that hormone replacement therapy ( HRT ) with a combination of estrogen-progestogen or with estrogen alone increases the risk of breast cancer. The increased risk depends on how long you use HRT. The increased risk is seen within 3 years. When treatment is stopped, the increased risk decreases over time, but it can persist for 10 years or more if you have used HRT for more than 5 years.
- Comparison
- Of 1,000 women aged 50 to 54 who do not take HRT, an average of 13 to 17 will be diagnosed with breast cancer over 5 years.
- In women who are 50 years old and start taking HRT with estrogen alone for 5 years, 16-17 cases per 1,000 users (i.e. 0-3 extra cases) will occur.
- In women who are 50 years old and start taking HRT with estrogen-progestogen for 5 years, there will be 21 cases per 1,000 users (i.e. 4-8 different cases).
- Among women aged 50–59 who do not use HRT, an average of 27 out of 1,000 will be diagnosed with breast cancer over 10 years.
- In women who are 50 years old and start taking HRT with estrogen alone for 10 years, 34 cases per 1,000 users (i.e. 7 extra cases) will occur.
- In women who are 50 years old and start taking HRT with estrogen-progestogen for 10 years, 48 cases per 1,000 users (i.e. 21 extra cases) will occur.
Check your breasts regularly. Contact a doctor if you notice changes such as:
- Indentations or pits
- Changes in the nipple
- Nodules you can see or feel
It is also recommended that you participate in a mammography examination when you are called to do so. At the mammogram, you must tell the nurse/healthcare professional who examines that you are using HRT, as this medicine may increase the density of the breasts. An increased breast density can make detecting lumps on mammography images more difficult.
- Ovarian cancer ( ovarian cancer )
- Ovarian cancer is rare – much rarer than breast cancer. Use of HRT with estrogen alone or combined estrogen-progestogen has been associated with a slightly increased risk of ovarian cancer.
- The risk of ovarian cancer varies with age. For example, the diagnosis of ovarian cancer will be made on about 2 women out of 2,000 aged 50 to 54 who do not take HRT for 5 years. For women who have taken HRT for 5 years, there will be about 3 cases per 2,000 users (i.e. about 1 extra case).
How HRT affects the heart and blood circulation
Blood clots in a vein ( thrombosis )
The risk of blood clots in the veins is 1.3–3 times higher for women who take HRT than those who do not, especially during the first year of treatment.
Blood clots can be serious. If a blood clot ends up in the lungs, it can cause chest pain, shortness of breath, collapse or even lead to death.
You are more likely to get a blood clot in a vein if the following apply to you. Tell your doctor if any of the following apply to you:
- You have not been able to walk or stand for a long time due to a major operation, injury or illness (see also section 3, “If you need surgery”)
- You are severely overweight ( BMI over 30 kg / m 2 )
- You have a coagulation disorder that requires long-term treatment with drugs that prevent blood clots.
- If a close relative has had a blood clot in the bone, lung, or another organ
- You have SLE (systemic lupus erythematosus)
- You have cancer
The symptoms of a blood clot are described in the section “You should contact a doctor immediately and stop the treatment.”
- Comparison
- For women in their 50s who do not take HRT, an average of 4-7 out of 1,000 people are expected to have a blood clot in a vein over 5 years.
- For women in their 50s who have taken HRT with estrogen-progestogen for more than 5 years, 9-12 out of 1,000 users are expected to get a blood clot in a vein (i.e. 5 cases).
- Whether varicose veins increase the risk of blood clots ( venous thrombosis ) is not known.
- Heart disease (heart attack)
- There is no evidence that HRT prevents heart attacks.
- For women over 60 who take HRT with estrogen-progestin, the risk of developing heart disease is slightly higher than those who do not take HRT.
- If you have had a heart attack or angina ( angina pectoris ), talk to your doctor about the benefits and risks of using Sequidot.
- Stroke
- The risk of stroke is about 1.5 times higher for those who take HRT than those who do not. The risk of stroke is age-dependent. Therefore, the number of stroke cases increases due to the use of HRT with increasing age.
- Comparison
- For women in their 50s who do not take HRT, an average of 8 out of 1,000 people are expected to have a stroke over 5 years.
- For women in their 50s who have taken HRT for more than 5 years, 11 out of 1,000 users are expected to have a stroke (i.e. 3 different cases).
Other conditions
- HRT can cause fluid to accumulate in the body ( edema ), especially in patients who already suffer from impaired heart or kidney function.
- HRT can cause an increase in blood lipid levels ( triglycerides ), which in women with elevated levels of blood lipids can lead to a risk of inflammation of the pancreas ( pancreatitis ). This can cause nausea, vomiting, upper abdomen pain, and fever.
- Using HRT does not prevent memory loss. The risk of memory loss may be slightly higher in women who start using HRT after age 65. Consult your doctor.
- All medicines used on the skin (such as patches ) can cause allergic skin reactions. Although it is rare, you should inform your doctor if you have severe allergic reactions to any ingredients in the Sequidot patch.
Other Medicines And Sequidot
Some medicines can affect the effect of Sequidot, which can lead to irregular bleeding. The following applies:
- Antiepileptic drugs (eg phenobarbital, phenytoin and carbamazepine)
- Medicines for tuberculosis (eg rifampicin, rifabutin)
- Medicines for HIV infection (eg nevirapine , efavirenz, ritonavir, telaprevir and nelfinavir)
- An herbal medicine containing St. John’s wort ( Hypericum perforatum )
- Other anti-infective drugs (e.g. ketoconazole, erythromycin)
- Medicines for hepatitis C virus ( HCV ) (such as the combination treatment ombitasvir/paritaprevir/ritonavir with or without dasabuvir as well as the treatment glekaprevir / pibrentasvir) may cause elevated liver function values in blood test results (increase in ALT liver enzyme) in women using combined hormonal contraceptives. Sequidot contains estradiol instead of Ethinyl estradiol. It is unknown whether an increase in ALT liver enzyme may occur when using Sequidot with this HCV combination therapy. Your doctor will advise you.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal remedies.
Results from blood tests analyze
If you need to take a blood sample, tell your doctor, or the person taking the blood sample, that you are using Sequidot, as it may affect the results of some tests.
Pregnancy And Breastfeeding
Sequidot is intended for women whose menstruation has stopped. If you become pregnant, stop using Sequidot and consult a doctor. Do not use Sequidot while breastfeeding.
Driving And Using Machines
No effects on the ability to drive and use machines have been reported with Sequidot.
You are responsible for assessing whether you can drive a motor vehicle or perform work requiring sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
How To Use Sequidot
Always use Sequidot exactly as your doctor has told you. Your doctor will strive to use the lowest dose, giving you symptom relief, and you should use Sequidot for the shortest time. Talk to your doctor if you do not get any relief from the symptoms or feel the dose is too high.
When to start treatment with Sequidot
- Suppose you do not have any other hormone replacement therapy ( patches or tablets) or have used continuous combined hormone replacement therapy (where estrogen and progestin are given continuously). In that case, you can start with Sequidot at the appropriate time.
- Suppose you are switching from a cyclic or sequential hormone replacement therapy (where progestin is given as a supplement for 12-14 days per treatment cycle). In that case, you can use the Sequidot Phase I patch the day after the end of the current treatment cycle. If you have menstrual bleeding at the end of each cycle, you can start with Sequidot on the first day of bleeding.
Treatment instructions for Sequidot phase I and phase II patches
- Each pack contains phase I patches (small rectangular with rounded corners) and phase II patches (round). Each treatment cycle is 4 weeks (two weeks with phase I and two weeks with phase II).
- Treatment begins with Sequidot Phase I patches (small rectangular). Use the Sequidot Phase I patch for the first 2 weeks. Change patches twice a week (every 3rd-4th day).
- After two weeks, change to Sequidot phase II patches in week 3 and continue throughout week 4. Also, change patches twice a week (every 3rd-4th day).
- It is best to always change the patch on the same day of the week each week (e.g. Monday and Thursday). Inside the Sequidot packaging, there is space to note down your dosing schedule. Select the two-day schedule that you intend to follow. Always change patches on the two days of the week you have marked.
- After completing the 4-week treatment cycle, start immediately on the next treatment cycle without interruption. It would help if you always had a patch on your skin.
Where should the Sequidot be attached?
Attach the patch to the lower abdomen below the waist. Avoid the waist, as the clothes can cause the patch to wear away.
You may need to try different places when you put on a new patch to find places that feel most comfortable and where clothes do not rub on the patch.
Never attach Sequidot to your breasts.
When changing patches, attach the new patch to another spot on the lower abdomen. Do not apply the patch in the same place twice in a row. It should take at least a week before the same skin surface is used again.
How Should Sequidot Be Attached?
If you store the patches in the refrigerator, allow the patch to reach room temperature before attaching it to the skin.
Before applying Sequidot, make sure the skin is:
- Clean, dry, and cool
- Free from powder, oil, moisturizer, or skin lotion
- Free from damage and irritation.
When changing patches, peel off the patch and fold it double with the adhesive side inwards. See section 5, “How to store Sequidot,” for instructions on safely disposing of the patch. Do not flush it down the toilet. If adhesive remains on the skin after removing the patch, you can remove it by gently rubbing it with an oil-based skin cream or lotion.
Other important information
Bathing, swimming, showering, and exercising should not affect the patch if applied correctly. If the patch should come off, e.g. during a bath or shower, shake off the water. Let the skin dry and cool, and apply the patch again, but not on the same skin surface (see “Where should Sequidot be attached?”).
Choose a clean, dry, non-lubricated skin surface. A new patch can be applied if the patch does not adhere properly to the skin. Regardless of which day this occurs, according to the schedule, you should return to changing patches on the same weekdays as usual.
The patch should be covered if exposed to direct sunlight or tanning beds. When bathing, the patch can be placed under the bathing suit.
The patch should not be applied to sweaty skin or immediately after bathing or showering. Wait until the skin is dry and cool.
How long should Sequidot be used?
You will see your doctor regularly and discuss the benefits and possible risks associated with Sequidot and whether you still need treatment. It is important that you go on regular return visits and that Sequidot is used only as long as there is a need.
If You Use More Sequidot Than You Should
You will get an unlikely overdose on Sequidot (as the patches release drugs continuously). If you have taken too much medicine or if, e.g. a child has accidentally taken medicine, remove the patch and contact a doctor or hospital for risk assessment and advice.
If You Forget To Use Sequidot
If you have forgotten to change the patch, apply a new one as soon as possible. Regardless of which day this occurs, you must change the patch according to the regular schedule.
Do not use two patches to compensate for a forgotten patch.
If you need surgery
If you are going to have surgery, tell your surgeon that you are using Sequidot. You may need to stop using Sequidot for 4 to 6 weeks before surgery to avoid the risk of blood clots (see section 2, “Blood clots in a vein ( thrombosis )”). Ask your doctor when it is appropriate to start using Sequidot again.
If You Stop Using Sequidot
When treatment with Sequidot is stopped, breakthrough bleeding or splashing bleeding may occur. If you experience breakthrough bleeding or splashing bleeding after stopping treatment, you should contact your doctor as soon as possible for an investigation and rule out uterine cancer.
After a long interruption, you should consult your doctor before using the patches again.
If you have any further questions about the use of this product, ask your doctor or pharmacist.
Possible Sequidot Side Effects
The following diseases are more common in women who take HRT than those who do not:
- Breast cancer
- Severe thickening of the uterine lining ( endometrial hyperplasia ) or cancer of the uterine lining (endometrial cancer)
- Ovarian cancer ( ovarian cancer )
- Blood clots in veins in bones or lungs (venous thromboembolism )
- Heart disease
- Stroke
- Probable memory loss, if treatment with HRT is started after the age of 65
See section 2 for more information on these side effects.
This medicine can cause side effects like all medicines, although not everybody gets them.
The following side effects have been noted with Sequidot:
Very common (may affect more than 1 user in 10)
- Headache
- Skin reactions to which the patch is applied, including
- Irritation
- Burning
- Rash
- Dryness
- Bleeding
- Bruising
- Inflammation
- Swelling
- Skin pigmentation
- Hives
- Blisters
- Chest tightness and pain
- Menstrual pain
- Bleeding disorders
Common (may affect up to 1 in 10 people)
- Depression
- Nervousness
- Mood swings
- Difficulty sleeping
- Nausea
- Acid reflux
- Diarrhea
- Abdominal pain
- Flatulence
- Acne
- Rash
- Dry skin and itching
- Swollen breasts
- Heavy menstrual bleeding
- White-yellow vaginal secretions
- Irregular vaginal bleeding
- Uterine cramps
- Inflammation of the abnormal uterus growth of the uterine lining
- Pain (e.g. back pain, pain in the legs and arms)
- Feeling of weakness
- Fluid accumulation in the arms and legs
- Weight change
Uncommon (may affect up to 1 in 100 people)
- Migraine
- Dizziness
- High blood pressure
- Vomiting
- Discoloration of the skin
- Impaired liver function
Rare(may affect up to 1 in 1,000 people)
- An ant crawls
- Blood clots
- Gallstones
- Hair loss
- Muscle weakness
- Muscle knots in the uterus
- Fluid blisters near the fallopian tubes
- Polyps in the cervix, altered sexual desire, and allergic reactions (including rash, itching, and difficulty breathing).
Very rare(may affect up to 1 in 10,000 people)
- Severe skin reaction
- Hives
- Impaired carbohydrate metabolism
- Involuntary movements of eyes, head, and neck
- Difficulty wearing contact lenses
- Signs of jaundice (yellowing of eyes and face)
- Pronounced hair growth
No known frequency (can not be calculated from the available data)
- Allergic skin inflammation
- Severe allergic reaction (including difficulty breathing, swelling of the face, tongue, throat or skin, dizziness and hives)
- Varicose veins
The following side effects have been reported with other HRTs:
- The disease of the gallbladder
- Various skin diseases:
- Dark skin spots, especially on the face and neck, so-called “pregnancy spots” (chloasma)
- Painful reddish-purple bumps on the skin (erythema nodosum)
- Annular redness or sore rash (erythema multiforme)
- Impaired memory and thought activity (possible dementia)
- Dry eyes
- Difficult to wear contact lenses
How To Store Sequidot
- Store in a refrigerator (2 ° C-8 ° C).
- The Sequidot can be stored at a maximum of 25 ° C for 6 months. Do not freeze.
- Store in the original packaging (sealed foil envelope). Use the patch immediately after opening.
- Both unused and used patches must be stored out of sight and reach of children.
- Do not use this medicine after the expiry date stated on the carton after EXP. The expiration date is the last day of the specified month.
- After the patch has been removed, it should be folded with the adhesive side inwards and stored safely so that children cannot access the patch. Return used or unused patches to pharmacies, preferably in the original packaging.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines that are no longer required. These measures will help to protect the environment.
Contents Of The Pack And Other Information
Content Declaration
- Phase I transdermal patch contains estradiol hemihydrate equivalent to 0.78 mg estradiol and releases approximately 50 micrograms of estradiol per 24 hours.
- Phase II transdermal patches contain estradiol hemihydrate equivalent to 0.51 mg estradiol and 4.80 mg norethisterone acetate and release approximately 50 micrograms of estradiol and 250 micrograms of norethisterone acetate per 24 hours.
- The active substance in Sequidot phase I transdermal patches is estradiol (as hemihydrate).
- The active substances in Sequidot Phase II transdermal patches are estradiol (as hemihydrate) and norethisterone acetate.
- Other ingredients in Sequidot phase I: Adhesive: Acrylic and silicone adhesive, oleyl alcohol, propylene glycol, povidone (E1201).Sequidot plaster film: Ethylene/vinyl acetate copolymer and vinylidene chloride/methyl acrylate copolymer laminate.Protective film (removed before application): Polyester film coated with a fluoropolymer.
- Other ingredients in Sequidot phase II: Adhesive: Acrylic and silicone adhesive, oleic acid, propylene glycol, and povidone (E1201).Patch film: Polyester film.Protective film (removed before application): Polyester film coated with a fluoropolymer.
What The Medicine Looks Like And The Contents Of The Pack
- Sequidot Phase I is a rectangular (5 cm 2 ) patch with rounded corners. The sequidot phase II patch is round (16 cm 2 ). Both patches contain a pressure-sensitive, adhesive layer that releases the active substances, with a translucent patch film on one side and a protective film on the other.
- Sequidot is supplied in cartons of 8 patches (4 phase I and 4 phase II) or 24 patches (12 phases I and 12 phases II).
- Not all pack sizes may be marketed.
Marketing Authorisation Holder:
Novartis Sverige AB, Box 1218, 164 28 Kista
Manufacturer:
Novartis Pharma GmbH
Roonstrasse 25
D-90429 Nuremberg
Germany
Novartis Pharmacéutica, SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain