Kyleena (19.5mg levonorgestrel)

Study details

After 3 years, 89% said they were 'very satisfied' or 'somewhat satisfied' with Kyleena.*

Study design

In this Phase III study, 2885 nulliparous and parous women aged 18–35 years were randomized to LNG‐IUS 8 (Jaydess▼ 13.5mg levonorgestrel) or LNG-IUS 12 (Kyleena) for 3 years.

*Study dates: From August 2007 through May 2008.

Adapted from: Gemzell-Danielsson K, et al. Eur J Obstet Gynecol Reprod Biol, 2017;210:22–28. 

Study details

After 3 years, 89% said they were 'very satisfied' or 'somewhat satisfied' with Kyleena.*

Study design

85.1% of women stated that they would continue with Kyleena after study completion if given the choice

*Study dates: From August 2007 through May 2008.

Adapted from: Gemzell-Danielsson K, et al. Eur J Obstet Gynecol Reprod Biol, 2017;210:22–28.

Kyleena^® (19.5mg intrauterine delivery system levonorgestrel) is an intrauterine system (IUS) indicated as a contraceptive for the prevention of pregnancy for up to 5 years.^[8]

Of the IUS available with a 5-year contraception license, Kyleena^® has the smallest T frame (28 x 30 mm) and narrowest insertion tube (3.8 mm).^[8][2]

In a multicentre study, a survey showed that 48% of women aged 18-44, and in particular young women (18-24 - 57%) forgot to take their contraceptive pill in the last 3 months. Kyleena^® can be beneficial for women who struggle to adhere to contraceptive compliance, e.g. taking the pill at the same time every day.^[9]

In the same survey, 87% of women mentioned that a method not requiring daily, weekly or monthly dosing would make things easier and 80% would consider switching contraceptives to minimise oestrogen exposure.^[9]

Cross-sectional survey completed by 5120 women.

A recent study of more than 6,000 women showed that 73% across all age ranges (18–49) would consider long-acting reversible contraception (LARC) if provided with substantial information from their healthcare professional on this method (compared with 38% estimated by healthcare professionals).^[10]

In general, patients are more positive about the idea of an LNG-IUS such as Kyleena^® after they receive education about them vs those who have not. This highlights the importance of effective counselling to increase awareness and knowledge.^[11]

A patient may feel reticent to have a Kyleena^® (19.5mg intrauterine delivery system levonorgestrel) inserted, this could be due to the following myths and misperceptions:

• 'Fitting and removal will be painful'. 80% of women perceive the placement procedure as painful^[12]
  • Some patients may feel pain or have some bleeding during insertion or removal^[8]
• 'The IUS will perforate and end up somewhere other than my uterus without me knowing'.
  • Perforation occurs in less than 1 in 100 women and can be detected by severe pelvic pain and continued heavy bleeding for more than a few weeks after insertion^[13]
• 'I will suffer years of irregular bleeding'
  • The chance of irregular bleeding is highest in the first 3-6 months.

Women have other perceptions of IUS which it is important to counsel them around:

• 63% of women consider having low/no hormones to be important when choosing contraception^[12]
• 30% of women are opposed to having something like a hormonal coil inserted in their body^[12]
• 37% of women feel they don’t know enough about hormonal coils^[12]

However, a study by Whitaker et al showed that adolescents and young women reported a positive attitude towards intrauterine contraceptives before and after a 3-minute educational intervention counselling tool. This included information about intrauterine contraception (IUC) effectiveness, insertion and removal process, risks, benefits, costs, effect on fertility, menstrual effects, length of use, similarities and differences between types of IUC available. Attitudes before and after the education intervention were assessed by questionnaire.^[11]

Patients included in the study: N=506 including 105 LARC users.

Kyleena^® contains 19.5mg levonorgestrel and has a mainly local progestogenic effect in the uterine cavity.^[8]

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones, for example:^[8]

• Medicines used to treat epilepsy / anticonvulsants / sedatives (e.g. phenytoin, topiramate, barbiturates, primidone, carbamazepine and oxcarbazepine).
• Certain antibiotics (e.g. rifampicin)
• Antifungal medicines (e.g. griseofulvin)
• Products containing St John's wort (a herbal remedy)

It is advised that prescribing information of concomitant medications should be consulted to identify potential interactions. For a full list of medicinal interactions and contraindications, refer to the Summary of Product Characteristics.

The majority of patients experience changes in menstrual bleeding pattern after insertion of Kyleena^® (19.5mg intrauterine delivery system levonorgestrel). Women can experience shorter, lighter periods versus before Kyleena^® insertion, and can experience amenorrhoea over 5 years. Very common side effects (more than 1 in 10 women) include:^[8][14]

• headache
• abdominal/pelvic pain
• acne/greasy skin
• bleeding changes including increased and decreased menstrual bleeding, spotting, infrequent periods and absence of bleeding
• ovarian cysts
• inflammation of the external genital organs and vagina (vulvovaginitis)

Common side effects (up to 1 in 10 women) include:^[14]

• depressed mood/depression
• migraine
• feeling sick (nausea)
• upper genital tract infection
• painful menstruation
• breast pain/discomfort
• device expulsion (complete and partial)
• hair loss
• genital discharge
• decreased libido
• dizziness
• increased weight

Kyleena can cause serious side effects, including:

Ectopic pregnancy and intrauterine pregnancy risks. There are risks if you become pregnant while using Kyleena (see “What if I become pregnant while using Kyleena?”).

Life‐threatening infection. Life­‐threatening infection can occur within the first few days after Kyleena is placed. Call your healthcare professional immediately if you develop severe pain or fever shortly after Kyleena is placed.

Pelvic inflammatory disease (PID). Some IUD users get a serious pelvic infection called pelvic inflammatory disease. PID is usually caused by a sexually transmitted infection. You have a higher chance of getting PID if you or your partner has sex with other partners. PID can cause serious problems such as infertility, ectopic pregnancy or pelvic pain that does not go away. PID is usually treated with antibiotics. More serious cases of PID may require surgery including removal of the uterus (hysterectomy). In rare cases, infections that start as PID can even cause death. Tell your healthcare professional right away if you have any of these signs of PID: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal (stomach area) pain, painful sex, chills, fever, genital lesions or sores.

Perforation. Kyleena may go into the wall of the uterus (become embedded) or go through the wall of the uterus. This is called perforation. If this occurs, Kyleena may no longer prevent pregnancy. If perforation occurs, Kyleena may move outside the uterus and can cause internal scarring, infection, or damage to other organs, and you may need surgery to have Kyleena removed. Excessive pain or vaginal bleeding during placement of Kyleena, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with perforation. The risk of perforation is increased if Kyleena is inserted while you are breastfeeding, or if you have recently given birth.

Expulsion. Kyleena may come out by itself. This is called expulsion. Expulsion occurs in about 4 out of 100 women. Excessive pain or vaginal bleeding during placement of Kyleena, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with expulsion. You may become pregnant if Kyleena comes out. If you think that Kyleena has come out, avoid intercourse or use a non-hormonal back-up birth control (such as condoms or spermicide) and call your healthcare professional. The risk of expulsion is increased with insertion right after delivery or second-trimester abortion.

For a full list of potential side effects, refer to the Summary of Product Characteristics and Patient Information Leaflet .

Educational Risk Minimisation Materials can be downloaded here to help reduce the risks associated with using Kyleena^®.

If the patient does experience side effects, they should speak to a doctor, pharmacist or nurse. This includes any possible side effects not listed in the contraception package leaflet.

Reporting adverse events and quality complaints

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/. Adverse events should also be reported to Bayer plc.

If you want to report an adverse event or quality complaint, reports can be directed to: Tel: 01182063500 or email: pvuk@bayer.com

Further information is available on the “contact” tab at www.bayer.co.uk.

Weight gain has been reported as a common side effect in patients with Kyleena^®.^[14]

For Mirena^® (52mg intrauterine delivery system levonorgestrel), very common undesirable effects (occurring in more than 10% of users) include uterine/vaginal bleeding, such as spotting, oligomenorrhoea and amenorrhoea. Undesirable effects are more common during the first months after the insertion and subside during prolonged use.^[15]

For Kyleena^® (19.5mg intrauterine delivery system levonorgestrel), very common undesirable effects include headaches, abdominal/pelvic pain, acne/seborrhoea, ovarian cysts, vulvovaginitis and bleeding changes including increased and decreased menstrual bleeding, spotting, infrequent bleeding and amenorrhoea. Over time, the frequency of amenorrhoea and infrequent bleeding increases, and the frequency of prolonged, irregular and frequent bleeding decreases.^[8]

For further information on Kyleena^® and Mirena^® please visit the Summary of Product Characteristics.

Effects on the menstrual bleeding pattern are expected in most users of Kyleena^®.^[8]

Irregular bleeding and spotting are common in the first months of use. Thereafter, the strong suppression of the endometrium results in the reduction of the duration and volume of menstrual bleeding. Scanty flow frequently develops into oligomenorrhoea or amenorrhoea.^[8]

Patients may have bleeding and spotting between menstrual periods, especially during the first months.

Overall, patients are likely to have a gradual reduction in the amount and number of days of bleeding each month. Some women eventually find that periods stop altogether,^[4] with 23% experiencing amenorrhoea at the end of Year 5.^[8]

When the intrauterine system (IUS) is removed, the patient’s menstrual cycle should return to normal.^[8]

Both Mirena^® and Kyleena^® affect patients’ bleeding patterns.

A phase 2, randomised, open-label study in 738 women compared the IUSs Jaydess^®▼ (13.5mg intrauterine delivery system levonorgestel)*, Kyleena^® and Mirena^® (with initial in vitro release rates of 12 μg/d, 16 μg/d and 20 μg/d respectively) and found that the bleeding profiles were similar in all groups, although total bleeding and spotting days decreased with increasing levonorgestrel dose.^[2]

^{*Jaydess®▼ (13.5mg intrauterine delivery system levonorgestel) Risk Minisation materials (RMM) Available online: https://www.medicines.org.uk/emc/product/5297/rmms}

The contraceptive efficacy of Kyleena^® (19.5mg intrauterine delivery system levonorgestrel) has been evaluated in a clinical study with 1,452 women aged 18–35 including 39.5% (574) nulliparous women of whom 84.0% (482) were nulligravid using Kyleena^®. The 1-year Pearl Index was 0.16 (95% confidence interval 0.02–0.58) and the 5-years Pearl Index was 0.29 (95% confidence interval 0.16–0.50). The failure rate was approximately 0.2% at Year 1 and the cumulative failure rate was approximately 1.4% at Year 5.¹

It is therefore, uncommon for a patient to become pregnant while using Kyleena^®, however, approximately half of the pregnancies that occur during Kyleena^®-use are likely to be ectopic.^[8]

The overall incidence of ectopic pregnancy in Phase II and III clinical trials with Kyleena^® was 0.2 per 100  women-years¹.

The possibility of an ectopic pregnancy must be carefully considered and evaluated. An ectopic pregnancy should be considered in the case of lower abdominal pain, especially in connection with missed periods or if an amenorrhoeic woman starts bleeding.^[8]

The use of a levonorgestrel-releasing intrauterine delivery system does not alter the course of future fertility. Upon removal of the intrauterine system, women return to their normal fertility.^[8]

It is uncommon for a woman to become pregnant while using Kyleena^®, however, approximately half of the pregnancies that occur during Kyleena^®-use are likely to be ectopic. If a patient does become pregnant while using Kyleena^®, ectopic pregnancy should be excluded and timely removal of the system is recommended, since any intrauterine contraceptive left in situ may increase the risk of miscarriage and preterm labour.

Women considering Kyleena^® should be counselled on the signs, symptoms and risks of ectopic pregnancy on an individual basis as an ectopic pregnancy may impact future fertility.

Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry an increased risk of ectopic pregnancy. 

If the patient wishes to continue the pregnancy and the system cannot be withdrawn, she should be informed about the risks and the possible consequences of premature birth of the infant. The course of such a pregnancy should be closely monitored.

The patient should be instructed to report all symptoms that suggest complications of the pregnancy, like cramping abdominal pain with fever.^[8]

For more information and a complete list of contraindications, refer to the Kyleena^® Summary of Product Characteristics

Insertion and removal of Kyleena^® (19.5mg intrauterine delivery system levonorgestrel) may be associated with some pain and bleeding. The procedure may precipitate a vasovagal reaction (e.g. syncope, or a seizure in an epileptic patient).^[8]

The National Institute for Health and Care Excellence guidelines for long-acting reversible contraceptives (LARC) recommends: ‘insertion of an IUS/IUD may cause pain and discomfort for a few hours and light bleeding for a few days, and patients should be informed about appropriate pain relief’.^[16]

Clinical guidance from the Faculty of Sexual and Reproductive Healthcare states that there is no evidence from current trials to support the use of topical lidocaine, misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) for improving ease of insertion or reducing pain during insertion of intrauterine methods. A discussion should be had on an individual basis on what pain relief may be required.

Managing your patient’s expectations with regards to pain is important and many healthcare professionals have found that talking to the patient throughout the fitting helps to reduce anxiety and makes them more comfortable. However, it is important to check with your patient if this would be helpful.

Kyleena^® (19.5mg intrauterine delivery system levonorgestrel), has a small T-frame (28 x 30 mm) placed using an inserter with narrow insertion tube (3.8 mm).^[2]

Kyleena^® may be suitable for women who would prefer a lower dose of levonorgestrel and do not require the added endometrial protection during oestrogen replacement therapy or treatment for menorrhagia. For an intrauterine delivery system that is licensed for these indications, refer to information on Mirena^® (52mg intrauterine delivery system levonorgestrel).

Kyleena^® and Jaydess^®▼ (13.5mg intrauterine delivery system levonorgestrel) are smaller (28 x 30 mm) than some other IUSs, for example Mirena^® (32 x 32 mm).

The IUS, Jaydess^®▼, contains 13.5mg levonorgestrel, Kyleena^®, contains 19.5mg levonorgestrel, a lower dose than Mirena^®, containing 52mg levonorgestrel.^[8][15][17] 

Kyleena^® is indicated as contraception for up to 5 years, compared with Jaydess^®▼, which is effective for 3 years and Mirena^® which is for up to 8 years. ^[8]

For more information about Bayer IUSs please visit the Risk Minimisation Materials.

Jaydess^®▼ prescribing information

Mirena^® prescribing Information

If the patient wishes to continue using the same method, a new system can be inserted at the same time (removal should be carried out at the same time. If pregnancy is not desired, removal should be carried out within 7 days of the onset of menstruation, provided the woman is experiencing regular menses. Kyleena can be replaced by a new system at any time in the cycle), in which case no additional protection is required provided the woman is experiencing regular menses.^[8]