Elonva Solution for Injection

Generic Name: Corifollitropin alfa (rch)
Product Name: Elonva Solution for Injection

Indication

Elonva is a medication used by women who are trying to get pregnant using in vitro fertilisation techniques. The medication stimulates the ovaries to develop multiple oocytes (eggs) in a single menstrual cycle (normally, the ovaries only develop one oocyte per cycle). The multiple eggs developed using this medication can then be removed from the ovaries (known as oocyte retrieval) and fertilised in a dish (in vitro).

For more information on stimulationg oocyte production, see Ovarian Stimulation and Hyperstimulation.

Action

The active ingredient in Elonva belongs to a group of hormones known as gonadotrophins. These are hormones which influence the functions of reproductive organs, including the organs involved in menstruation and pregnancy. Elonva works in the same way as follicle stimulating hormone (FSH), which the body produces naturally during the menstrual cycle. FSH promotes the maturation of oocytes in ovarian follicles, which are located within the ovaries.

The body naturally produces enough FSH to support the maturation of one oocyte per menstrual cycle. In a natural menstrual cycle, when fully matured, the egg is released from the woman’s ovaries in the process known as ovulation.

When a woman takes Elonva, extra FSH is added to her body and there is a sufficient quantity of the hormone to support the development of more than one oocyte per menstrual cycle. Elonva is administered with a view to oocyte removal – that is, the surgical removal of the matured oocytes from the ovaries. It is taken in combination with other drugs that prevent the mature oocytes being released from the ovaries into the fallopian tubes, as they would be in a natural menstrual cycle.

Dose advice

Dose information

Medical supervision

Elonva should be used only under close supervision of a doctor who has special training in providing infertility treatment. You can administer the injection yourself (or have your partner or another person you trust administer the injection), but the person who injects Elonva for you must be trained how to do it. They must also follow the doctor’s advice about how much Elonva should be injected and when the injection should be given.

Before injecting the drug, it is important to look carefully at the solution. It should be clear and not have any solid particles in it (even if the particles are tiny). If the solution is discoloured or contains particles, it should not be injected and should be returned to the doctor or pharmacy.

Dose and administration

Elonva is usually administered as part of a combined Elonva and GnRH antagonist (a medicine that stops the secretion of reproductive hormones) regime, which means that after the Elonva injection, women also receive treatment with GnRH antagonists (usually one week afterwards).

When Elonva is taken in combination with a GnRH antagonist, the recommended dose depends on your body weight. Those who weight ≤ 60 kg should receive a single 100 μg dose. Those weighing > 60 kg should be given 150 μg. A single injection containing the correct dose of Elonva is administered once per treatment cycle. Your doctor will advise you on the dose most appropriate for you.

Elonva induces greater ovarian follicle development than other types of FSH used in assisted reproduction treatment cycles, and taking too much Elonva can be very dangerous. Always take the dose recommended by your doctor and ensure you return to the doctor at the scheduled time for an ultrasound to assess follicular development.

Elonva solution is packaged in glass syringes, containing 0.5 mL of solution. Each package contains a sterile needle for injection, which should be disposed of after use. Concentration is either 100 μg of corifollitropin alfa (100 μg / 0.5 mL) or 150 μg of corifollitropin alfa (150 μg / 0.5 mL). The medicine is injected subcutaneously (under the skin), usually into your abdominal wall.

Timing of administration in relation to other drugs used in assisted reproduction

Elonva administration

Elonva is administered in the early follicular phase of the menstrual cycle (the first phase of the menstrual cycle which begins with menstrual bleeding). Elonva increases the extent and number of ovarian follicles that develop in the follicular phase.

The day on which Elonva is administered becomes Day 1 of the ovarian stimulation cycle or assisted reproduction cycle. Following Elonva administration, ovarian follicles mature for 5–6 days and no other medicines are administered in this time.

GnRH antagonist administration

On Day 5–6 of the stimulation cycle, your doctor will use ultrasound to assess the extent to which ovarian follicles have developed. This assessment allows the doctor to determine the most appropriate time to administer a GnRH antagonist, which promotes final maturation of oocytes and prepares them for retrieval and fertilisation.

While the GnRH antagonist helps oocytes mature, it also prevents their release from their follicles (ovulation) by preventing levels of luteinisng hormone (LH) from rising. LH levels naturally rise in the luteal phase of the menstrual cycle to catalyse ovulation. Administering GnRH antagonist-containing medications allows ovarian follicles more time to mature, which increases the number of follicles that develop a mature oocyte per cycle and therefore the number of oocytes that can be retrieved for laboratory fertilisation.

Follicle stimulating hormone (FSH) administration

FSH, a hormone which is similar to the hormone contained in Elonva but does not have a sustained action and so works for only a day, may be administered seven days after Elonva (on Day 8 of the simulation cycle). Daily injections of FSH are continued until ovarian follicles have developed sufficiently for oocyte retrieval (when at least three ovarian follicles have grow to ≥ 17 mm). If ovarian follicles are already adequately matured from the effects of Elonva, FSH may not be administered.

The correct dose depends on how many ovarian follicles have begun to mature and how big they are. Typically, 150 IU of FSH is administered daily until adequate follicular development is observed, usually on Day 9 of the stimulation cycle (range 6–18 days).

Administration of human chorionic gonadotrophin (hCG)

When adequate oocyte maturation is achieved, 500–1,000 IU of human chorionic gonadotrophin (hCG) is administered in a single injection. hCG starts the final process of oocyte maturation and also prevents oocyte release from their ovarian follicles. In cases of excessive ovarian responsive, hCG administration may be omitted and the treatment cycle cancelled in order to avoid ovarian hyperstimulation syndrome (a potentially fatal condition that can arise following ovarian stimulation).

If you have any queries about the correct way to use Elonva, please ask your doctor.

Contraindications

Elonva should not be used under certain conditions. Tell your doctor if you have:

Tumours of the ovaries, breast, uterus, pituitary gland or hypothalamus;
Irregular vaginal bleeding, the cause of which has not been diagnosed;
Primary ovarian failure (your ovaries do not produce mature eggs and you do not ovulate);
Ovarian cysts or enlarged ovaries;
History of ovarian hyperstimulation syndrome;
Previously experienced excessive follicular growth (the growth of too many ovarian follicles) whilst undergoing ovarian stimulation. Excessive follicular growth is defined as the development of > 30 ovarian follicles ≥ 11 mm is size;
Uterine fibroids (benign tumours in the uterus) which mean that you cannot get pregnant;
Distortions of the reproductive organs which mean you cannot get pregnant (e.g. an abnormally shaped womb);
You are pregnant or breastfeeding;
You are allergic to the active ingredient or other ingredients in the solution.

Precautions

Before treatment

Before deciding on Elonva treatment, your doctor will need to assess the causes underlying your infertility to ensure Elonva is an appropriate medicine for your treatment. Your doctor will also inform you of the risks associated with assisted reproductive treatments. These risks are not specific to Elonva, but relate instead to all types of assisted reproduction. The discussion of risks and benefits may include:

Advice about the increased likelihood of achieving a multiple pregnancy in assisted reproduction, and the risks this creates for a mother and her foetuses;
The increased risk of congenital abnormalities associated with assisted reproductive techniques;
The increased risk of neoplasms of the reproductive organs in women who undergo multiple ovarian stimulation cycles. A causal relationship between ovarian stimulation drugs and reproductive neoplasms has not yet been established or ruled out.

When starting treatment

Special care needs to be taken when using Elonva under certain conditions. Tell your doctor if you have:

Conditions which may make pregnancy unsafe for you, including:
- Hypothyroidism (reduced hormone production by the thyroid gland);
- Adrenocortical deficiency (deficiency in hormones produced by the adrenal gland);
- Hyperprolactinaemia (excessive concentrations of the hormone prolactin in the blood); and
- Pituitary or hypothalamic tumours (tumours in the hormone producing glands of the brain);
Already taken Elonva in the current infertility treatment cycle. Elonva should only be administered once per treatment cycle;
Taken follicle stimulating hormone (FSH) in the same treatment cycle. FSH should not be administered within seven days of an Elonva injection (it is, however, sometimes administered in the same treatment cycle, more than seven days after the administration of Elonva);
Kidney disorder;
Polycystic ovarian syndrome (PCOS): There is no evidence that the drug is safe and effective for women with PCOS;
Risk of thromboembolism (blood clots): The risk of blood clots is increased with use of gonadotrophin therapies (including Elonva). Your doctor will need to carefully assess the risks and benefits of Elonva. Conditions which increase the risk of thromboembolism include:
- Personal history of thromboembolism;
- Family history of thromboembolism;
- Thrombophilia (excessive blood clotting);
- Severe obesity (BMI > 30 kg/m²);
Taken medications containing GnRH agonists: The development of ovarian follicles increases when the two medicines are taken together and there is a risk of ovarian hyperstimulation syndrome;
Ovarian hyperstimulation syndrome risk;
Treatment cycle: If you are undergoing your first assisted reproduction treatment cycle, your risk of ovarian hyperstimulation syndrome is unknown, and your doctor will need to monitor you ovarian response more closely in the two weeks following Elonva administration.

Monitoring ovarian follicular development

As a precaution against ovarian hyperstimulation syndrome, your doctor will monitor the development of your ovarian follicles after you have taken Elonva. This means you will have to have several ultrasounds. Your doctor will count the number of follicles developing within the ovaries and measure their size. Your doctor may also do a blood test to check for concentrations of oestrogen.

Women who develop > 18 ovarian follicles measuring ≥ 11 mm have an increased risk of developing ovarian hyperstimulation syndrome. Changes to the medications usually given in the week after Elonva administration may be needed to ensure these woman do not experience ovarian hyperstimulation syndrome. Women who develop over 30 ovarian follicles measuring ≥ 11 mm following Elonva administration have a particularly high risk.

When a woman has a high risk of ovarian hyperstimulation syndrome, the doctor may:

Withhold further gonadotrophin administration for three days: This is known as coasting. Your doctor will not give you FSH injections, which are usually given for several days after the Elonva injection starts to wear off (from Day 8 of the cycle). FSH promotes continued follicular development;
Decide not to administer hCG, usually given at least 7 days after Elonva, which stimulates the final maturation of oocytes and prepares the womb to receive a fertilised oocyte (which is replaced to the womb after fertilisation in the laboratory). In this case, the treatment cycle is cancelled and the oocytes are not removed from the ovaries in that treatment cycle. This occurs in situations where the woman has a very high risk of ovarian hyperstimulation syndrome;
Delay administration of hCG until blood oestrogen levels return to normal. In this case, there is a delay in the final maturation and retrieval of oocytes;
Administer a lower dose of hCG than they usually would;
Cryopreserve all embryos for use in a future treatment cycle, instead of administering additional medications which prepare the womb to receive a fertilised oocyte.

Precautions to take if you get pregnant following ovarian stimulation with Elonva

If you get pregnant after using Elonva as part of your assisted reproduction, you will need to return to your doctor for another ultrasound, so that the doctor can assess the location of the growing embryo. In all types of assisted reproduction there is an increased risk of extra-uterine pregnancy, which is pregnancy that occurs outside the womb (e.g. in the fallopian tubes).

Extra-uterine pregnancies are not viable, meaning that the fertilised egg cannot grow into a foetus or a baby. Extra-uterine pregnancies are very dangerous and must be terminated (if they do not result in spontaneous miscarriage, which in most cases they do). Ultrasound assessment allows the doctor to identify and terminate an extra-uterine pregnancy early, while the risks to your health are lowest.

Pregnancy

Elonva is a Pregnancy Category B3 medication. The drug should not be used by pregnant women.

Breastfeeding

Elonva should not be used by women who are breastfeeding.

Children

Elonva should not be used by children.

Schedule

Elonva is a Schedule 4 medication.¹

Common side effects

All medicines have side effects. Most commonly the side effects are minor; however, some can be more serious. Usually the benefits of taking a medication outweigh the associated side effects. Your doctor would have considered these side effects before starting you on Elonva.

Common side effects

Common side effects are those that occur in 1–10% of people given Elonva. These include:

Ovarian hyperstimulation syndrome (5.2%);
Pelvic pain (4.1%);
Discomfort (5.5%);
Headache (3.2%);
Nausea (1.7%);
Fatigue (1.4%); and
Breast complaints (including tenderness) (1.2%).

Uncommon side effects

Side effects that occur in less than 1% of people given Elonva are considered uncommon. People do not necessarily experience any of these side effects, so do not become alarmed by this list:

Dizziness;
Abdominal pain;
Vomiting;
Diarrhoea;
Constipation; and
Abdominal distention (swollen abdomen);
Ovarian torsion (twisting of the ovaries which restricts blood supply).

If you experience any of the listed side effects, or any other symptoms that appear abnormal or unusual, please tell your doctor.

References

Elonva [online]. St Leonards, NSW: MIMS Online. 21 July 2010 [cited 28 October 2010]. Available from: URL link
Elonva Consumer Medicine Information. North Ryde, NSW: Schering-Plough Pty Ltd; July 2010.