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Premarin
estrogens, conjugated
Black Box Warnings .
Endometrial Cancer with Unopposed Estrogen in Patients with Intact Uterus
unopposed estrogen use incr. risk of endometrial CA in patients with intact uterus; adding progestogen has been shown to decr. risk of endometrial hyperplasia, a possible precursor to endometrial CA; perform adequate diagnostic measures (including directed or random endometrial sampling) to rule out malignancy in menopausal patient with abnormal genital bleeding of unknown etiology
Adult Dosing .
Dosage forms: TAB: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg; INJ: various
vasomotor symptoms, moderate-severe menopausal
- [0.3-1.25 mg PO qd]
- Start: 0.3 mg PO qd; Info: use lowest effective estrogen dose, shortest effective treatment duration; may cycle 25 days on, 5 days off; consider adding progestogen if intact uterus
vulvovaginal atrophy, moderate-severe menopausal
- [0.3-1.25 mg PO qd]
- Start: 0.3 mg PO qd; Info: not preferred if local symptoms only; use lowest effective estrogen dose, shortest effective treatment duration; may cycle 25 days on, 5 days off; consider adding progestogen if intact uterus
osteoporosis prevention, postmenopausal
- [0.3-0.625 mg PO qd]
- Start: 0.3 mg PO qd; Info: weigh estrogen treatment risk/benefit; may cycle 25 days on, 5 days off; consider adding progestogen if intact uterus
hypoestrogenism
- [associated with hypogonadism]
- Dose: 0.625-1.25 mg PO qd; Info: titrate to lowest effective maintenance dose; add progestogen if intact uterus
- [associated with oophorectomy or primary ovarian failure]
- Dose: 1.25 mg PO qd; Info: titrate to lowest effective maintenance dose; add progestogen if intact uterus
metastatic breast CA, palliative tx
- [10 mg PO tid for at least 3mo]
advanced prostate CA, palliative tx
- [1.25-2.5 mg PO tid]
abnormal uterine bleeding, acute
- [25 mg IM/IV q4-6h x24h]
- Info: IV route preferred over IM route
uremic bleeding (off-label)
- [0.6 mg/kg/dose IV qd x5 days]
renal dosing
- [see below]
- renal disease: not defined, caution advised
- HD/PD: not defined, caution advised
hepatic dosing
- [see below]
- hepatic impairment: contraindicated
Peds Dosing .
- Dosage forms: TAB: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, 1.25 mg; INJ: various
puberty induction, female
- [associated with hypogonadism, 11 yo and older]
- Dose: 0.625-1.25 mg PO qd; Start: 0.15 mg PO qd, then may incr. dose q6-12mo; Info: add progesterone micronized or medroxyprogesterone after breakthrough bleeding occurs or with at least 2 years of estrogen treatment if intact uterus; after puberty induction, titrate to lowest effective maintenance dose for hypoestrogenism until menopausal age
- [associated with constitutional causes, 13 yo and older (off-label)]
- Dose: 0.15 mg PO qd x3-6mo; Info: may incr. dose after 6mo if spontaneous puberty progression not achieved; reassess need for treatment q3-6mo
abnormal uterine bleeding, acute (off-label)
- [postmenarchal patients]
- Dose: 25 mg IM/IV q4-6h x24h; Info: IV route preferred over IM route
renal dosing
- [not defined]
- renal impairment: consider adult renal dosing for guidance
- HD/PD: consider adult renal dosing for guidance
hepatic dosing
- [not defined]
- hepatic impairment: consider adult hepatic dosing for guidance
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- pregnancy (INJ form)
- hepatic disease
- hepatic impairment
- vaginal bleeding, undiagnosed
- breast CA
- breast CA history
- cancer, estrogen-dependent
- cancer history, estrogen-dependent
- venous thromboembolism
- venous thromboembolism history
- arterial thromboembolism within 12mo
- protein C deficiency
- protein S deficiency
- thrombophilic disorder
- caution: patients 65 yo and older
- caution: renal disease
- caution: cardiovascular disease
- caution: vascular disease risk
- caution: HTN
- caution: diabetes mellitus
- caution: smokers
- caution: smoking habit change
- caution: hypertriglyceridemia
- caution: obesity
- caution: surgery
- caution: immobilization, prolonged
- caution: gallbladder disease
- caution: cholestatic jaundice history, estrogen-associated
- caution: cholestatic jaundice history, pregnancy-associated
- caution: hypothyroidism
- caution: sensitivity to fluid retention
- caution: hypocalcemia, severe
- caution: endometriosis
- caution: migraine
- caution: chorea
- caution: seizure disorder
- caution: asthma
- caution: porphyria
- caution: SLE
- caution: hepatic hemangioma
- caution: angioedema, hereditary
- caution: contraceptive use, latex (vaginal cream form)
- caution: contraceptive use, rubber (vaginal cream form)
Drug Interactions .
Overview
estrogens, conjugated (hormone replacement)
estrogen
- CYP1A2 substrate
- CYP3A4 substrate
- P-gp substrate
- CYP1A2 inhibitor, moderate
- UGT1A4 inducer
- estrogen
- hyperglycemic effects
- interferes w/ ACTH analog test
- thrombogenic effects
- thyroid hormone synthesis/metabolism effects
Contraindicated
- fezolinetant
Avoid/Use Alternative
- alosetron
- bendamustine
- clomiphene
- estradiol (contraceptive)
- estrogens, conjugated (hormone replacement)
- estrogens, esterified (hormone replacement)
- ethinyl estradiol (hormone replacement)
- exemestane
- ospemifene
- pirfenidone
- raloxifene
- tamoxifen
- tizanidine
- toremifene
- tranexamic acid
- vaccinia immune globulin
Monitor/Modify Tx
- abemaciclib
- abrocitinib
- acarbose
- aflibercept
- aminocaproic acid
- aminophylline
- anthrax immune globulin
- anti-inhibitor coagulant complex
- antihemophilic factor (factor VIII)/von Willebrand factor complex
- asciminib
- asparaginase
- atidarsagene autotemcel
- avatrombopag
- axitinib
- baricitinib
- bevacizumab
- bexagliflozin
- binimetinib
- botulism immune globulin
- brolucizumab
- bromocriptine
- C1 esterase inhibitor
- cabozantinib
- caffeine citrate
- calaspargase
- canagliflozin
- carbamazepine
- carfilzomib
- celecoxib
- chorionic gonadotropin
- clozapine
- coagulation factor IX
- coagulation factor VIIa
- coagulation factor XIII A-subunit
- colesevelam
- concizumab
- cosyntropin
- cytomegalovirus immune globulin
- danazol
- dapagliflozin
- darbepoetin alfa
- deflazacort
- desogestrel (contraceptive)
- deuruxolitinib
- dexamethasone
- diclofenac
- diclofenac topical
- dienogest (contraceptive)
- diflunisal
- drospirenone (contraceptive)
- dulaglutide
- eltrombopag
- empagliflozin
- epirubicin
- epoetin alfa
- ertugliflozin
- etodolac
- etonogestrel (contraceptive)
- everolimus
- exenatide
- factor XIII concentrate
- faricimab
- fedratinib
- fenofibrate
- fenofibric acid
- fenoprofen
- fibrinogen (human)
- fitusiran
- flurbiprofen
- follitropin
- fruquintinib
- glimepiride
- glipizide
- glyburide
- hepatitis B immune globulin
- hydrocortisone
- ibuprofen
- immune globulin
- indomethacin
- insulin
- iodixanol
- iohexol
- iomeprol
- iopamidol
- iopromide
- iothalamate meglumine
- ioversol
- ketoprofen
- ketorolac
- lazertinib
- lenalidomide
- levonorgestrel (contraceptive)
- levothyroxine
- linagliptin
- liothyronine
- liraglutide
- lixisenatide
- luspatercept
- lusutrombopag
- meclofenamate
- medroxyprogesterone (contraceptive)
- mefenamic acid
- megestrol
- meloxicam
- menotropins
- metformin
- methoxy polyethylene glycol-epoetin beta
- methyltestosterone
- metyrapone
- miglitol
- momelotinib
- nabumetone
- naproxen
- nateglinide
- necitumumab
- nintedanib
- norelgestromin (contraceptive)
- norethindrone (contraceptive)
- norgestimate (contraceptive)
- norgestrel (contraceptive)
- obinutuzumab
- olaparib
- oxaprozin
- pacritinib
- pazopanib
- pegaspargase
- pioglitazone
- piroxicam
- ponatinib
- porfimer
- propranolol
- prothrombin complex concentrate (human)
- ranibizumab
- rasagiline
- repaglinide
- Rho(D) immune globulin
- ritlecitinib
- romiplostim
- ropinirole
- rosiglitazone
- ruxolitinib
- ruxolitinib topical
- salsalate
- saxagliptin
- segesterone (contraceptive)
- semaglutide
- sipuleucel-T
- sitagliptin
- sodium tetradecyl sulfate
- somapacitan
- somatrogon
- somatropin
- sotatercept
- sulindac
- tesamorelin
- testosterone
- thalidomide
- theophylline
- thyroid
- tirzepatide
- tivozanib
- tofacitinib
- tolmetin
- trametinib
- tretinoin
- triclabendazole
- upadacitinib
- vadadustat
- valoctocogene roxaparvovec
- valproic acid
- vamorolone
- varicella zoster immune globulin
- von Willebrand factor
- vorinostat
- warfarin
- ziv-aflibercept
- zopapogene imadenovec
Caution Advised
- apalutamide
- betamethasone
- butalbital
- caffeine
- cortisone
- danshen
- dantrolene
- dicloxacillin
- duloxetine
- efavirenz
- elacestrant
- elagolix
- encorafenib
- enzalutamide
- fosphenytoin
- fulvestrant
- grapefruit
- icosapent ethyl
- imlunestrant
- ivosidenib
- lorlatinib
- lumacaftor/ivacaftor
- melatonin
- meropenem
- methylprednisolone
- mitotane
- oxcarbazepine
- pentobarbital
- phenobarbital
- prednisolone
- prednisone
- primidone
- ramelteon
- relugolix
- rifabutin
- rifampin
- rifapentine
- riluzole
- ritonavir
- roflumilast
- roflumilast topical
- romidepsin
- selegiline
- St. John's wort
- tipranavir
- turmeric
- ursodiol
- vaborbactam
- zolmitriptan
Adverse Reactions .
Serious Reactions
- thromboembolism
- retinal thrombosis
- MI
- stroke
- HTN
- breast CA
- ovarian CA
- endometrial CA
- endometrial hyperplasia
- uterine fibroid enlargement
- hypercalcemia, severe (metastatic breast CA patients)
- cholestatic jaundice
- gallbladder disease
- pancreatitis
- hepatic hemangioma enlargement
- depression
- dementia
- migraine
- chorea exacerbation
- seizure disorder exacerbation
- asthma exacerbation
- porphyria aggravation
- SLE exacerbation
- anaphylaxis
- anaphylactoid reaction
- angioedema
- erythema multiforme
- erythema nodosum
- ischemic colitis
Common Reactions
- vaginal bleeding
- vaginal spotting
- abdominal cramps
- abdominal distension
- nausea
- vomiting
- breast changes
- breast pain
- cervical secretion changes
- headache
- migraine
- pain
- asthenia
- fluid retention
- BP elevated
- mood changes
- candidiasis, vulvovaginal
- glucose intolerance
- weight changes
- libido changes
- contact lens intolerance
- vision changes
- rash
- melasma
- chloasma
- alopecia
- hirsutism
- acne
- breast development (vaginal cream form in peds patients)
Safety/Monitoring .
Monitoring Parameters
PO Route: free T4, free T3 if hypothyroidism tx; breast exam q12mo; mammography, frequency variable (age, risk factors, prior results); bone maturation/epiphyseal status if bone growth incomplete (adolescents); BP regularly
IM/IV Route: BP
Look/Sound-Alike Drug Names
Premarin confused with: Prempro; Prevacid; Primaxin; Provera; Remeron
conjugated estrogens confused with: esterified estrogens; Estratest
Pregnancy/Lactation .
Pregnancy
Clinical Summary
INJ Formulations: contraindicated during pregnancy; risk of teratogenicity low when inadvertently used during 1st trimester based on human data with PO form
All Other Formulations: N//A; drug unlikely to be used during pregnancy based on indication
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; possible risk of decr. infant wt based on conflicting human data; possible decr. milk production, especially during early postpartum, based on limited human data and drug's mechanism of action
Pharmacology .
Metabolism: for estrogen: liver; CYP450: 3A4 (partial) substrate; Info: enterohepatically recirculated; converted to active estrogen metabolites including estradiol, estrone
Excretion: for estrogen: urine; Half-life: 1-2h (estradiol), 4-18h (estrone)
Subclass: Estrogens, Non-oncologic ; Hormonal Oncologics, Estrogens ; Osteoporosis: Estrogenic Agents ; Uremic Bleeding
Mechanism of Action
for estrogen: binds to estrogen receptors, developing and maintaining female sex characteristics and reproductive systems
Formulary .
No Formulary Selected
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