Sayana

/ Pfizer

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. For instructions on how to prepare SAYANA® before administration, and how to administer SAYANA®, see section 5.4 at the attached doctor’s leaflet.
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.
Further Doses: The second and subsequent injections should be given at 13-week intervals, as long as the injection is given no later than seven days after this time, no additional contraceptive measures (e.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.
If the patient is breast-feeding, the injection should be given no sooner than six weeks post partum, when the infant’s enzyme system is more developed.
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.
Switching from other Methods of Contraception: When switching from other contraception methods, SAYANA® should be given in a manner that ensures continuous contraceptive coverage based upon the mechanism of action of both methods (e.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. As SAYANA® largely undergoes hepatic elimination, it may be poorly metabolised in patients with severe liver insufficiency.
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.
Pediatric Population: SAYANA® is not indicated before menarche. Data in
adolescent females (12-18 years) is available for IM administration of MPA. 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.

SAYANA® is indicated for long-term female contraception. Each subcutaneous injection prevents ovulation and provides contraception for at least 13 weeks (+/-1 week). However, it should be taken into consideration that the return to fertility (ovulation) may be delayed for up to one year.
Since loss of bone mineral density (BMD) may occur in females of all ages who use SAYANA® longterm, a risk/benefit assessment, which also takes into consideration the decrease in BMD that occurs during pregnancy and/or lactation, should be considered.
Use in Adolescents (12-18 years): In adolescents, use of SAYANA® is only indicated when other contraceptive methods are considered unsuitable or unacceptable, due to unknown long-term effects of bone loss associated with SAYANA® during the critical period of bone accretion.
SAYANA® has not been studied in women under the age of 18 years but data are available for intramuscular depot-medroxyprogesterone acetate (DMPA-IM) 150mg in this population.

Patients with a known hypersensitivity to MPA or any of its excipients.
Pregnancy is known or suspected.
Women with known or suspected malignancy of the breast or genital organs.
Patients with undiagnosed vaginal bleeding.
Patients with severe hepatic impairment.
Patients with metabolic bone disease.
Patients with active thromboembolic disease and in patients with current or past history of cerebrovascular disease.

Weight Changes: Weight changes are common but unpredictable. In the phase 3 studies body weight was followed over 12 months. Half (50%) of women remained within 2.2 kg of their initial body weight. 12% of women lost more than 2.2 kg, and 38% of women gained more than 2.3 kg.
Fluid Retention: There is evidence that progestogens may cause some degree of fluid retention, and as a result, caution should be exercised in treating any patient with a pre-existing medical condition that might be adversely affected by fluid retention.
Return of Ovulation: Following a single dose of SAYANA®, the cumulative rate of return to ovulation as measured by plasma progesterone was 97.4% (38/39 patients) by one year after administration. After the 14-week therapeutic window, the earliest return to ovulation was one week, and the median time to ovulation was 30 weeks. Women should be counseled that there is a potential for delay in return to ovulation following use of the method, regardless of the duration of use. It is recognised, however, that amenorrhoea and/or irregular menstruation upon discontinuation of hormonal contraception may be due to an underlying disorder associated with menstrual irregularity, especially polycystic ovarian syndrome.
Psychiatric Disorders: Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use. Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
Protection against Sexually Transmitted Infections: Women should be counselled that SAYANA® does not protect against sexually transmitted infections (STIs) including HIV infection (AIDS) but equally, DMPA is a sterile injection and, used as directed, will not expose them to STIs. Safer sex practices including correct and consistent use of condoms reduce the transmission of STIs through sexual contact, including HIV.
The benefits of contraceptive options and their risks must be evaluated individually for each woman.
Carbohydrate/Metabolism: Some patients receiving progestogens may exhibit a decrease in glucose tolerance. Diabetic patients should be carefully observed while receiving such therapy.
Liver Function: If jaundice develops in any woman receiving SAYANA®, consideration should be given to not readminister the medication.
Hypertension and Lipid Disorders: Limited evidence suggests that there is a small increased risk of cardiovascular events among women with hypertension or with lipid disorders who used progestogen-only injectables. If hypertension occurs under SAYANA® treatment and/or the increase in hypertension cannot adequately be controlled by antihypertensive medication, treatment with SAYANA® should be stopped. Additional risk factors for arterial thrombotic disorders include: hypertension, smoking, age, lipid disorders, migraine, obesity, positive family history, cardiac valve disorders, atrial fibrillation.
SAYANA® should be used cautiously in patients with one or more of these risk factors.
Other Conditions: The following conditions have been reported both during pregnancy and during sex steroid use, but an association with the use of progestagens has not been established: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss.
If any of the conditions/risk factors mentioned is present, the benefits of SAYANA use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether SAYANA use should be discontinued.
Laboratory Tests: The pathologist should be advised of progestogen therapy when relevant specimens are submitted. The physician should be informed that certain endocrine and liver function tests, and blood components might be affected by progestogen therapy:
a) Plasma/urinary steroids are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).
b) Plasma and urinary gonadotropin levels are decreased (e.g., LH, FSH).
c) Sex-hormone-binding-globulin (SHBG) concentrations are decreased.
Excipients: As this product contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, it may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm. This medicinal product contains less than 1 mmol sodium (23 mg) per 104 mg/0.65 mL, i.e., essentially ‘Sodium-free’.
See prescribing information for full details.

The most frequently (>5%) reported adverse drug reactions were headache (8.9%), metrorrhagia (7.1%), weight increased (6.9%), amenorrhoea (6.3%) and injection site reactions (any type, 6.1%).
See prescribing information for full details.

No interaction studies have been performed with SAYANA®.
Interactions with other medical treatments (including oral anticoagulants) have rarely been reported, but causality has not been determined. The possibility of interactions should be borne in mind in patients receiving concurrent treatment with other drugs.
MPA is metabolized in vitro primarily by hydroxylation via the CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4 inducers or inhibitors on MPA have not been conducted and therefore, the clinical effects of CYP3A4 inducers or inhibitors are unknown.

Pregnancy: SAYANA is contraindicated in women who are pregnant. Some reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female fetuses. If SAYANA is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be warned of the potential hazard to the fetus.
Lactation: Low detectable amounts of drug have been identified in the milk of mothers receiving MPA. In nursing mothers treated with DMPA-IM (150 mg), milk composition, quality, and amount are not adversely affected. Neonates and infants exposed to MPA from breast milk have been studied for developmental and behavioural effects through puberty. No adverse effects have been noted.
However, due to limitations of the data regarding the effects of MPA in breastfed infants less than six weeks old, SAYANA® should be given no sooner than six weeks post partum when the infant’s enzyme system is more developed.
See prescribing information for full details.

No positive action is required other than cessation of therapy.