SAYANA

2 Therapeutic indications SAYANA is indicated for long-term female contraception. Each subcutaneous injection prevents ovulation and provides contraception for at least 13 weeks (+/- 1 week). 4). 4), a risk/benefit assessment, which also takes into consideration the decrease in BMD that occurs during pregnancy and/or lactation, should be considered.

4). SAYANA has not been studied in women under the age of 18 years but data are available for intramuscular depot-medroxyprogesterone acetate (DMPA-IM) 150 mg in this population. 2 Posology and method of administration The prefilled syringe of SAYANA should be vigorously shaken just before use to ensure that the dose being given represents a uniform suspension.

The treatment should be initiated by a doctor or healthcare assistant and administered as a subcutaneous injection (SC) into the anterior thigh or abdomen. The medication should be injected slowly until the syringe is empty, which should take about 5-7 seconds.

6.

Step 1:

Choosing and preparing the injection area. Choose the injection area in either the upper thigh or abdomen, see shaded areas (Diagram 1). Avoid bony areas and the umbilicus. Upper thigh or abdomen Diagram 1 Use an alcohol pad to wipe the skin in the injection area you have chosen.

Allow the skin to dry. While continuing to hold the syringe barrel firmly, remove the protective plastic needle cover from the needle without twisting, making sure the needle is still firmly attached to the syringe (Diagram 2). Diagram 2 While holding the syringe with the needle pointing upward, gently push in the plunger until the medicine is up to the top of the syringe.

There should be no air within the barrel (Diagram 3).

Diagram 3 Step 2:

Injecting the dose. Gently grasp and squeeze a large area of skin in the chosen injection area between the thumb and fore-finger, pulling it away from the body. Insert the needle at a 45 degree angle so that most of the needle is in the fatty tissue.

The plastic hub of the needle should be nearly or almost touching the skin (Diagram 4). Diagram 4 Inject the medication slowly until the syringe is empty (Diagram 5). • This should take about 5-7 seconds. • It is important that the entire dose of Sayana is given Inject slowly (5-7 seconds) Diagram 5 When the entire dose is completely injected, gently pull the needle out of the skin.

Use a clean cotton pad to press lightly on the injection area for a few seconds. Do NOT rub the area.

Adults First Injection:

To provide contraceptive cover in the first cycle of use, an injection of 104 mg SC should be given during the first five days of a normal menstrual cycle. If the injection is carried out according to these instructions, no additional contraceptive measure is required.

g. barrier) are required. If the interval from the preceding injection is greater than 14 weeks (13 weeks plus 7 days) for any reason, then pregnancy should be excluded before the next injection is given. The efficacy of SAYANA depends on adherence to the recommended dosage schedule of administration.

Post Partum:

If the patient is not breast-feeding, the injection should be given within 5 days post partum (to increase assurance that the patient is not pregnant). If the injection is to be given at another time then pregnancy should be excluded.

6). There is evidence that women prescribed SAYANA in the immediate puerperium can experience prolonged and heavy bleeding. Because of this, the drug should be used with caution in the puerperium. Women who are considering use of the product immediately following delivery or termination should be advised that the risk of heavy or prolonged bleeding may be increased.

Doctors are reminded that in the non breast-feeding, post partum patient, ovulation may occur as early as week 4. g. patients switching from oral contraceptives should have their first injection of SAYANA within 7 days after their last active pill).

Hepatic impairment:

The effect of hepatic disease on the pharmacokinetics of SAYANA is unknown. 3 – Contraindications).

Renal impairment:

The effect of renal disease on the pharmacokinetics of SAYANA is unknown. No dosage adjustment should be necessary in women with renal insufficiency, since SAYANA is almost exclusively eliminated by hepatic metabolism. 1 Therapeutic Indications).

Data in adolescent females (12-18 years) is available for IM administration of MPA (see section

Events from clinical trials:

The table below provides a listing of adverse drug reactions with frequency based on all-causality data from clinical studies that enrolled 2053 women who received DMPA-SC for contraception. 1%). Adverse reactions are listed according to the following categories.

4) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

1 Pharmacodynamic properties). Other than concerns about loss of BMD, the safety and effectiveness of SAYANA is expected to be the same for adolescents after menarche and adult females. 1. • SAYANA is contra-indicated if pregnancy is known or suspected.

• SAYANA is contra-indicated in women with known or suspected malignancy of the breast or genital organs. • SAYANA is contra-indicated in patients with undiagnosed vaginal bleeding. • SAYANA is contra-indicated in patients with severe hepatic impairment.

• SAYANA is contra-indicated in patients with metabolic bone disease. • SAYANA is contra-indicated in patients with active thromboembolic disease and in patients with current or past history of cerebrovascular disease. • SAYANA is contra-indicated in patients with meningioma or history of meningioma.

4 Special warnings and precautions for use Loss of Bone Mineral Density: Use of depot-medroxyprogesterone acetate subcutaneous (DMPA-SC) reduces serum estrogen levels and is associated with significant loss of BMD due to the known effect of estrogen deficiency on the bone remodelling system.

Bone loss is greater with increasing duration of use, however BMD appears to increase after DMPA-SC is discontinued and ovarian estrogen production increases. This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion.

e. after menopause. A study to assess the BMD effects of DMPA-IM (Depo-Provera) in adolescent females showed that its use was associated with a statistically significant decline in BMD from baseline. 1). However, in some participants, BMD did not fully return to baseline during follow-up and the long-term outcome is not known in this group.

In adolescents, SAYANA may be used, but only after other methods of contraception have been discussed with the patients and considered to be unsuitable or unacceptable. A large observational study of predominantly adult female contraceptive users showed that use of DMPA-IM did not increase risk for bone fractures.

1 – Relationship of fracture incidence to use of DMPA-IM by women of reproductive age). In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out in those who wish to continue use for more than 2 years.

In particular, in women with significant lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be considered prior to use of SAYANA. 1. Adequate intake of calcium and Vitamin D, whether from the diet or from supplements, is important for bone health in women of all ages.

Menstrual Irregularities:

Most women using SAYANA experienced alteration of menstrual bleeding patterns. Patients should be appropriately counselled concerning the likelihood of menstrual disturbance and the potential delay in return to ovulation. As women continued using SAYANA, fewer experienced irregular bleeding and more experienced amenorrhea.

After receiving the fourth dose, 39% of women experienced amenorrhea during month 6. 5% of women experienced amenorrhea. The changes in menstrual patterns from the three contraception trials are presented in Figures 1 and 2. Figure 1 shows the increase in the percentage of women experiencing amenorrhea over the 12 month study.

Figure 2 presents the percentage of women experiencing spotting only, bleeding only, and bleeding and spotting over the same time period. In addition to amenorrhea, altered bleeding patterns included intermenstrual bleeding, menorrhagia and metrorrhagia.

If abnormal bleeding associated with SAYANA persists or is severe, appropriate investigation and treatment should be instituted. Figure 1. 5 0 10 20 30 40 50 60 70 80 90 100 1 Ns:1831 2 1854 3 1840 4 1729 5 1717 6 1689 7 1544 8 1550 9 1520 10 1413 11 1404 12 1273 Month Percent Figure 2.

Percent of SAYANA -Treated Women with Bleeding and/or Spotting per 30- Day Month Contraception Studies (ITT Population, N=2053) Cancer Risks: Long-term case-controlled surveillance of DMPA-IM 150 mg users found no overall increased risk of ovarian, liver, or cervical cancer and a prolonged, protective effect of reducing the risk of endometrial cancer in the population of users.

Breast cancer is rare among women under 40 years of age whether or not they use hormonal contraceptives. Results from some epidemiological studies suggest a small difference in the risk of having the disease in current and recent users compared with never-users.

Any excess risk in current and recent DMPA users is small in relation to the overall risk of breast cancer, particularly in young women (see below), and is not apparent after 10 years since last use. Duration of use does not seem to be important.

Possible number of additional cases of breast cancer diagnosed up […]

1. • SAYANA is contra-indicated if pregnancy is known or suspected. • SAYANA is contra-indicated in women with known or suspected malignancy of the breast or genital organs. • SAYANA is contra-indicated in patients with undiagnosed vaginal bleeding.

• SAYANA is contra-indicated in patients with severe hepatic impairment. • SAYANA is contra-indicated in patients with metabolic bone disease. • SAYANA is contra-indicated in patients with active thromboembolic disease and in patients with current or past history of cerebrovascular disease.

• SAYANA is contra-indicated in patients with meningioma or history of meningioma.