Infertility Drug Summary

Drug	Dosage	Remarks
Danazol	200-800 mg PO 24 hourly x 3-6 months	Adverse Reactions Dermatologic effects (acne, oily skin, mild hirsutism, hair loss, rash); CNS effects (nervousness, headache, vertigo, emotional lability, backache, skeletal muscle spasm); Other effects (flushing, breast size reduction, voice changes, nausea, weight gain) Special Instructions Use with caution in patients with cardiac, renal or hepatic dysfunction, epilepsy, migraine Avoid use in pregnant or breastfeeding patients, patients with undiagnosed abnormal genital bleeding or marked hepatic impairment

Drug	Dosage	Remarks
Cetrorelix	For controlled ovarian stimulation in conjunction with gonadotropins: 3 mg SC given on stimulation day 7 (when serum estradiol level shows appropriate stimulation response)  If hCG is not administered within 4 days after injection, continue 0.25 mg at 96-hour intervals until hCG is administered or 0.25 mg SC on day 5 or morning of day 6 and continued daily until hCG is administered	Adverse Reactions CNS effect (headache); Hormonal effect (OHSS); GI effect (nausea); Hepatic effect (increase in liver enzyme); Other effects (anaphylactic reactions, local injection site reactions) Special Instructions Avoid use in pregnant or breastfeeding patients, patients with moderate to severe renal and hepatic impairment or severe allergic conditions Use with caution in patients with active allergic conditions or history of allergies Injection site should be at the lower abdomen, preferably around the navel
Ganirelix (Synthetic decapeptide  ganirelix)	For controlled ovarian hyperstimulation in conjunction with gonadotropins: 0.25 mg SC 24 hourly starting on day 5 or day 6 of FSH or Corifollitropin alfa administration  Controlled ovarian hyperstimulation with FSH or Corifollitropin alfa may start at day 2 or 3 of menses	Adverse Reactions GI effects (nausea, abdominal distension); Obstetric effects (pelvic pain, OHSS, ectopic pregnancy, miscarriage); Other effects (local injection site reactions, headache)  Special Instructions Avoid use in pregnant patients, patients with severe renal or hepatic impairment or hypersensitivity to GnRH or any GnRH analogues Use with caution in patients with OHSS, women weighing <50 kg or >90 kg  Early ultrasound confirmation that pregnancy is intrauterine is important

Drug	Dosage	Remarks
Bromocriptine	Initial dose: 1.25-2.5 mg PO 8-12 hourly or 24 hourly at bedtime  Increase dose slowly in increments of 1.25-2.5 mg/day every 2-3 days Maintenance dose: 2.5-15 mg/day PO in divided doses Max dose: 30 mg/day	Adverse Reactions Usually dose related; GI effects (nausea/vomiting); CNS effects (dizziness, headache, syncope, headache, seizures, psychosis, hallucinations, delusions, confusion); CV effects (orthostatic hypotension that may occur at the beginning of treatment, digital vasospasm, leg cramps, prolonged hypotension, arrhythmia, chest pain, pericarditis and pericardial effusions, very rarely hypertension, Ml, stroke); Other effects (retroperitoneal fibrosis, pleural thickening and effusions, nasal congestion, dry mouth)  Studies have shown that Cabergoline may be better tolerated than Bromocriptine Special Instructions Take with food to minimize nausea Use with caution in patients with CV disease, psychiatric disorders and in postpartum women with history of hypertensive disorders
Cabergoline	Initial dose: 0.5 mg PO once weekly or 0.25 mg PO 2x/week  May increase dose slowly in increments of 0.5 mg/week at monthly intervals Maintenance dose: 0.25-0.5 mg PO 1-2x/week  Max dose: 4.5 mg/week  Doses over 1 mg should be given in divided doses

Drug	Dosage	Remarks
Estradiol	1-2 mg PO 24 hourly cyclically or  As valerate: 10-20 mg IM 4 weekly or 1 patch applied 1-2 weekly	Adverse Reactions Gynecological effects (breast, endometrial and ovarian cancers, endometrial hyperplasia, breakthrough bleeding and spotting); Metabolic effects (increased thyroid binding globulin levels); CV effects (stroke, MI, pulmonary embolism, hypertension, deep venous thromboembolism [DVT]); Other effect (dementia)  Special Instructions Patch: Applied on a clean, dry area of skin of the upper buttock or lower abdomen  Avoid use in patients with history or current breast cancer, CV disorders, untreated endometrial hyperplasia, estrogen-dependent tumors, undiagnosed vaginal bleeding, thrombophilic disorders, migraine  Use with caution in patients with history of endometrial hyperplasia, risk factors for CV disorders, cholestatic jaundice; systemic lupus erythematosus, hepatic hemangiomas, epilepsy, asthma
Estriol	0.5-1 mg PO 24 hourly on days 6-15 of menstrual cycle	Adverse Reactions GI effects (nausea/vomiting, abdominal cramps, bloating, diarrhea, appetite/weight changes); Hormonal effects (breast tenderness, breast enlargement, libido changes); Metabolic effects (glucose intolerance, hypocalcemia, increased serum triglycerides); CV effects (edema, hypertension, venous thromboembolism [VTE]); CNS effects (headache, irritability, mental depression, nervousness); Other effect (anaphylactic reactions)   Special Instructions Avoid use in patients with known or suspected estrogen-dependent tumors, undiagnosed vaginal bleeding, thrombosis Use with caution in patients with CV disease, epilepsy, migraine, severe liver disorders, with history of hypertensive disorders, breast cancer, endometrial carcinoma

Drug	Dosage	Remarks
Choriogonadotropin alfa	For ovulation induction and ART: 250 mcg SC given 1-2 days after the last dose of follicle-stimulating agent or hMG	Adverse Reactions CNS effect (headache); Dermatologic effects (acne, rash); Hormonal effects (ovarian hyperstimulation, uterine bleeding); GI effects (abdominal discomfort, nausea); Local effect (injection site reaction) Thromboembolic events have been reported in association with or separate from OHSS Atelectasis, asthma exacerbation, acute respiratory distress syndrome have been reported after Follitropin alfa, beta and delta, Menotropin, or Urofollitropin’s use Special Instructions Avoid use in pregnant patients, patients with high FSH level indicating primary gonadal failure, uncontrolled non-gonadal endocrinopathies, abnormal vaginal bleeding of unknown origin, ovarian cysts or enlargement, or in patients with ovary, breast, uterus, hypothalamus or pituitary gland tumors Lutropin alfa or Menotropin should be used with caution in patients with hepatic or renal impairment Advise patient on the possibility of multiple births
Chorionic gonadotropin	For ovulation induction or preparation of follicles for puncture: 1 injection of 5,000-10,000 IU IM to complete treatment with an FSH-containing preparation  For luteal phase support: 1,000-5,000 IU IM on the third, sixth and ninth day following ovulation
Corifollitropin alfa	Stimulation Day 1:  Women ≤60 kg or ≤36 years old: 100 mcg SC single dose during the early follicular phase of the menstrual cycle  Women >60 kg or >36 years old: 150 mcg SC single dose during the early follicular phase of the menstrual cycle  Stimulation Day 5-6: GnRH antagonist should be started depending on ovarian response  Stimulation Day 8: May continue with daily injection of FSH until criteria for triggering oocyte maturation have been reached; may administer hCG 5,000-10,000 IU as soon as 3 follicles ≥17 mm are observed to induce final oocyte maturation
Follitropin (Recombinant human FSH)	For controlled ovarian stimulation for multiple follicular development prior to ART: 150-300 IU SC/IM 24 hourly starting on days 2-5 of the menstrual cycle
Follitropin alfa1	For ovulation induction: 75-150 IU SC/IM 24 hourly May increase dose by 37.5 IU (up to 75 IU) at 7- or 14-day intervals until adequate response is achieved  Max dose: 225 IU/day  Once adequate response is achieved, administer hCG 5,000-10,000 IU 1-2 days after FSH injection For controlled ovarian stimulation prior to ART: 150-225 IU SC/IM 24 hourly starting on day 2 or 3 of the menstrual cycle  May adjust dose based on response  Max dose: 450 IU/day Administer single dose of hCG 5,000-10,000 IU 1-2 days after the last FSH injection to induce final follicular maturation
Follitropin beta	For ovulation induction:  50 IU/day SC/slow IM for 7-14 days  For controlled ovarian stimulation prior to ART: 100-225 IU/day SC/IM for 4 days, then adjusted individually based on ovarian response Maintenance dose: 75-375 IU SC/IM for 6-12 days  Max dose: 450 IU/day
Follitropin delta	Individualized dose based on AMH  and body weight Serum AMH*  <15 pmol/L (<2.03 ng/mL): 12 mcg SC 24 hourly 15-16 pmol/L (2.03-2.3 ng/mL): 0.19 mcg/kg SC 24 hourly  17 pmol/L (2.31-2.44 ng/mL): 0.18 mcg/kg SC 24 hourly 18 pmol/L (2.45-2.58 ng/mL): 0.17 mcg/kg SC 24 hourly  19-20 pmol/L (2.59-2.86 ng/mL): 0.16 mcg/kg SC 24 hourly 21-22 pmol/L (2.87-3.14 ng/mL): 0.15 mcg/kg SC 24 hourly  23-24 pmol/L (3.15-3.42 ng/mL): 0.14 mcg/kg SC 24 hourly 25-27 pmol/L (3.43-3.84 ng/mL): 0.13 mcg/kg SC 24 hourly  28-32 pmol/L (3.85-4.54 ng/mL): 0.12 mcg/kg SC 24 hourly 33-39 pmol/L (4.55-5.52 ng/mL): 0.11 mcg/kg SC 24 hourly  ≥40 pmol/L (≥5.53 ng/mL): 0.1 mcg/kg SC 24 hourly Max dose: 12 mcg SC 24 hourly for first treatment cycle *According to the calibration based on activity assay, 1 mcg of Follitropin delta = 15 IU of Follitropin alfa Doses to be initiated 2-3 days after menstruation and continued until adequate follicular development has been achieved (≥3 17 mm follicles are observed)  Once adequate response is achieved, administer a single dose of rhCG 250 mg or hCG 5,000 IU
Lutropin alfa1  (Recombinant human LH)	For ovulation induction:  75 IU/day SC with 75-150 IU FSH  May increase FSH if required by 37.5-75 IU increments at 7- to 14-day intervals Duration of stimulation in any one cycle may be extended up to 5 weeks until adequate response is achieved  Once optimal response is obtained, administer hCG 5,000-10,000 IU 1-2 days after LH and FSH injection to induce ovulation
Menotrophin (Highly-purified human menopausal  gonadotrophin, HP-hMG, Menotropin)	For ovulation induction: 75 IU FSH/75 IU LH - 150 IU FSH/150 IU LH SC/IM 24 hourly  May adjust dose gradually until adequate response is achieved  Max dose: 225 IU/day  To induce ovulation, administer hCG 5,000-10,000 IU IM 1-2 days after the last dose of hMG injection For controlled ovarian stimulation prior to ART: 75 IU FSH/75 IU LH - 300 IU FSH/300 IU LH SC/IM 24 hourly starting on day 2-3 of menstrual cycle Max dose: 450 IU/day  Max duration: 20 days Continue until adequate response is achieved 1-2 days after adequate response, inject 10,000 IU of hCG and oocyte retrieval is performed 32-36 hours later
Urofollitropin	For ovulation induction:  75-150 IU/day IM/SC x 7-12 days followed by hCG  Max dose: 225 IU/day  For controlled ovarian stimulation prior to ART: 150-225 IU SC 24 hourly during first 5 days of treatment  Max dose: 450 IU/day  Once an optimal response is obtained, inject 10,000 IU of hCG for follicular maturation for oocyte retrieval

¹Combination of Follitropin alfa and Lutropin alfa is available. Please see the latest MIMS for the specific formulations and prescribing information.

Drug	Dosage	Remarks
Goserelin (Goserelin acetate)	3.6 mg depot injection SC to down-regulate pituitary gland every 28 days	Adverse Reactions Hypoestrogenism that manifests as transient vaginal bleeding, hot flushes, vaginal dryness, decreased libido, breast tenderness, insomnia, depression, irritability, fatigue, decreased elasticity of the skin, headache, osteoporosis after several weeks of treatment; GI effects (nausea, abdominal discomfort); Other effects (reduction in glucose tolerance, changes in serum lipids and hepatic effects, hypersensitivity reactions)  Special Instructions Addback strategy with Estrogen/Progesterone can eliminate most of these side effects Monitor bone density during long-term treatment
Triptorelin	0.1 mg SC 24 hourly from the second day of menstrual cycle  ART: 0.5 mg SC for 7-10 days followed by 0.1 mg SC 24 hourly or  3.75 mg SC/IM as single dose on cycle day 2 or 3 (follicular phase) or day 22 (luteal phase)  Gonadotropin should be started after desensitization of the pituitary, generally about 15 days after injection

Drug	Dosage	Remarks
Dydrogesterone	10 mg PO 24 hourly from day 14-25 of cycle  Treatment should be maintained for at least 6 consecutive cycles	Adverse Reactions GI effects (GI disturbances, change in weight/appetite); Breast changes (enlargement, secretion, discomfort); Androgenic effects (acne, mental depression, changes in libido, hair loss, hirsutism, irregular menstrual bleeding); Other effects (fluid retention, edema, fatigue, alterations in lipid profile)  Special Instructions Should not be used if woman is pregnant, experiencing unexplained vaginal bleeding or known or suspected to have breast cancer Use with caution in women with CV or renal impairment, DM, asthma, epilepsy, migraine, depression, pruritus related to cholestasis, VTE and in patients with other conditions that may be aggravated by edema or hepatic impairment
Hydroxyprogesterone  (Hydroxyprogesterone  caproate)	250 mg IM about 3 days after the rise in basal body temperature
Progesterone	200-300 mg PO divided 12-24 hourly  May increase up to 600 mg/day PO divided 8 hourly

Drug	Available Strength	Dosage	Remarks
Progesterone	8% vaginal gel	1 application 24 hourly starting after documented ovulation or arbitrarily on day 18-21 of cycle  When used during IVF, daily application should be continued for 1 month if there is laboratory evidence of pregnancy  Recommended duration of therapy: 12 cycles	Adverse Reactions GI effects (constipation, diarrhea, nausea/vomiting, abdominal pain, change in weight/appetite); GU effects (perineal pain, nocturia); Breast changes (enlargement, pain); CNS effects (somnolence, headache, nervousness, depression); Androgenic effects (acne, mental depression, changes in libido, hair loss, hirsutism, irregular menstrual bleeding); Other effect (arthralgia) Special Instructions Vaginal tab: Insert applicator into the vagina in a sitting or lying position Should not be used if woman is pregnant, experiencing unexplained vaginal bleeding or known or suspected to have breast cancer Use with caution in women with CV or renal impairment, DM, asthma, epilepsy, migraine, depression, pruritus related to cholestasis, VTE and in patients with other conditions that may be aggravated by edema or hepatic impairment
	400 mg pessary	For luteal phase support: 400 mg inserted vaginally or rectally 12-24 hourly  Start at oocyte retrieval and continue for 38 days for confirmed pregnancy
	100 mg vaginal tab, cap 200 mg vaginal cap	1 tab/cap inserted vaginally 12 hourly to be started within several days of ovulation  May increase in weekly increments of 100 mg/day  Max dose: 600 mg/day spread over 3 doses

Drug	Dosage	Remarks
Clomifene  (Clomifene citrate,  Clomiphene)	First course: 50 mg PO 24 hourly x 5 days starting on or about the fifth day of the menstrual cycle or at any time if there is amenorrhea  If ovulation does not occur:  Second course: 100 mg PO 24 hourly x 5 days  May be given starting 30 days after the previous course  If ovulatory menses do not occur, the dose may be repeated for 2 additional cycles  Max duration: 6 cycles	Adverse Reactions Incidence and severity tend to be dose dependent: Ovarian effects (reversible enlargement, cyst formation, OHSS); Hormonal effects (vasomotor flushes, breast tenderness, abnormal uterine bleeding, endometriosis, weight gain); GI effects (abdominal pain, bloating); CNS effects (convulsions, dizziness, lightheadedness, headache, nervous tension, fatigue, vertigo, insomnia, depression); Visual effects (transient visual disturbances eg after-images blurring; rarely cataracts and optic neuritis); Other effects (rarely allergic reactions and reversible hair loss) Increased risk of multiple births though rarely more than twins, ectopic pregnancy Special Instructions Contraindicated in patients with liver disease, undiagnosed abnormal uterine bleeding, hormone-dependent tumors, and patients with pre-existing mental depression or thrombophlebitis Patients should be properly informed of the possibility of multiple pregnancy  Monitor for abdominal and pelvic pain which may be a sign of enlarged ovarian cyst Discontinue use if visual disturbances develop
Tamoxifen	First course: 10 mg PO 12 hourly or 20 mg PO 24 hourly x 4 days on days 2-5 of the menstrual cycle  May be increased to 40 mg/day then  80 mg/day for subsequent courses if ovulation does not occur  For irregular cycles: Start first course on any day with subsequent course starting 45 days later or  On day 2 of cycle if menstruation occurs	Adverse Reactions Hormonal effects (hot flushes, fluid retention, vaginal bleeding and discharge, suppression of menses in some premenopausal women, pruritus vulvae); Hematologic effects (increased tendency for thromboembolism and pulmonary embolism, transient decreased platelet, leukopenia); CNS effects (headache, lightheadedness, depression, confusion, fatigue); GI effects (nausea/vomiting, GI discomfort, elevated liver enzymes); Visual effects (blurred vision, rarely corneal changes, cataracts, retinopathy); Dermatologic effects (dry skin, rashes, vasculitis); Metabolic effect (hypertriglyceridemia); Rarely severe allergic reactions Special Instructions Avoid in women with history of thromboembolic events Should be stopped at least 6 weeks before surgery and before any long-term immobility and started only once fully mobile

All dosage recommendations are for non-elderly adults with normal renal and hepatic function unless otherwise stated. 
Not all products are available or approved for above use in all countries. 
Products listed in the Drug Summary are based on indications stated in the locally approved product monographs. 
Please refer to local product monographs in Related MIMS Drugs for country-specific prescribing information.