Makena

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Makena

Classes

Progestogens

Administration

Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Hydroxyprogesterone caproate injection is a clear, yellow solution. It is viscous and oily. Do not use if solid particles appear or if the solution is cloudy.

Intramuscular Administration

Administer hydroxyprogesterone caproate injection from the vial intramuscularly. DO NOT administer intravenously.
 
Intramuscular injection (generic products, 250 mg/mL)
Because of the low viscosity of the vehicle, may administer with a small gauge needle. Inject deeply into the upper outer quadrant of the gluteal muscle following the usual precautions for IM injection.
The injection provides a high concentration in a small volume; particular care should be taken to administer the full dose.
Storage of multiple-dose vials: Storage instructions may vary between products; refer to the product label for specific storage information.

Adverse Reactions
Severe

thromboembolism / Delayed / 0-1.0
anaphylactoid reactions / Rapid / Incidence not known
myocardial infarction / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
stroke / Early / Incidence not known
optic neuritis / Delayed / Incidence not known
retinal thrombosis / Delayed / Incidence not known

Moderate

dyspnea / Early / Incidence not known
cystitis / Delayed / Incidence not known
anovulation / Delayed / Incidence not known
vaginal bleeding / Delayed / Incidence not known
edema / Delayed / Incidence not known
hypertension / Early / Incidence not known
fluid retention / Delayed / Incidence not known
migraine / Early / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
depression / Delayed / Incidence not known

Mild

nausea / Early / 1.0-10.0
injection site reaction / Rapid / 10.0
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known
cough / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
vomiting / Early / Incidence not known
weight loss / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
hirsutism / Delayed / Incidence not known
leukorrhea / Delayed / Incidence not known
breakthrough bleeding / Delayed / Incidence not known
libido increase / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
melasma / Delayed / Incidence not known
dizziness / Early / Incidence not known
back pain / Delayed / Incidence not known
headache / Early / Incidence not known
fatigue / Early / Incidence not known
diplopia / Early / Incidence not known
emotional lability / Early / Incidence not known

Common Brand Names

Makena

Dea Class

Rx

Description

A progestin for intramuscular administration
Used to treat amenorrhea, dysfunctional uterine bleeding, and advanced endometrial cancer
Makena (and its approved generics) was withdrawn from the market because postmarketing studies did not confirm efficacy for preterm delivery prophylaxis

Dosage And Indications
For the treatment of inoperable, recurrent, and metastatic endometrial cancer. Intramuscular dosage Adult females

1,000 mg or more per week IM (range 1 gram IM once weekly to 1 gram IM once daily). Discontinue when relapse occurs, or after 12 weeks with no objective response. May be used in advanced stage concomitantly with other anticancer therapy (surgery, a radiation, or chemotherapy, or combination of these). Treatment results reported to date have been better in histologically well-differentiated forms of endometrial adenocarcinoma.

For the treatment of amenorrhea (primary or secondary) or for dysfunctional uterine bleeding due to hormonal imbalance in the absence of organic pathology. Intramuscular dosage Adult and Adolescent females

375 mg IM as a single dose, given at any time. Next dose may begin after 4 days of desquamation or, if there is no bleeding, 21 days after the initial single dose. If no response after 4 cycles, discontinue. The number of cycles used and when to use cyclic dosing is dependent on the indication for use and whether estrogen therapy is used concurrently. A suggested cyclic cycle with estrogen is as follows (28-day cycle; repeated every 4 weeks) Day 1 of each cycle: Estradiol Valerate Injection (20 mg IM); then, 2 weeks after Day 1: Hydroxyprogesterone Caproate 250 mg IM; then Estradiol Valerate (5 mg IM) 4 weeks after Day 1: This is Day 1 of the next cycle. Repeat as indicated. If estrogen deficiency has been prolonged in patients with amenorrhea, menstruation may not occur until estrogen has been given for several months. Discontinue when cyclic therapy no longer required.

To test for endogenous estrogen production ("Medical D and C"). Intramuscular dosage Adult females

250 mg IM once; repeat for confirmation at 4 weeks after the first injection. Discontinue after the second dose. Bleeding should occur 7 to 14 days after the injection.

Dosing Considerations
Hepatic Impairment

Hydroxyprogesterone is contraindicated for use in patients with active hepatic disease.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed; use with caution.

Drug Interactions

Acarbose: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Alogliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Alogliptin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Alogliptin; Pioglitazone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Antidiabetic Agents: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Atazanavir; Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Bromocriptine: (Minor) Bromocriptine is used to restore ovulation and ovarian function in amenorrheic women. Hydroxyprogesterone can cause amenorrhea and, therefore, counteract the desired effects of bromocriptine. Concurrent use is not recommended.
Canagliflozin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Canagliflozin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Chlorpropamide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Dapagliflozin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Dapagliflozin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Dapagliflozin; Saxagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Darunavir; Cobicistat: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Dulaglutide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Elbasvir; Grazoprevir: (Moderate) Administering hydroxyprogesterone with elbasvir; grazoprevir may result in elevated hydroxyprogesterone plasma concentrations. Hydroxyprogesterone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider the benefits and risk of administering antiretroviral regimens containing cobicistat with hydroxyprogesterone caproate. Insufficient data are available to make dosage recommendations, particularly when cobicistat is combined in other antiviral regimens. It is not clear how cobicistat alters various progestin-only agents used for contraception, fertility or luteal support, or for hormone replacement therapy (HRT). Instruct women to report any breakthrough bleeding or other adverse effects (e.g., insulin resistance, dyslipidemia, and acne) to their prescribers. There is a potential for altered efficacy for combined hormonal contraceptives. Consider alternative methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS. When progestins are used for other purposes, monitor for altered clinical response to hormonal therapy.
Empagliflozin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Empagliflozin; Linagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Empagliflozin; Linagliptin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Empagliflozin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Ertugliflozin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Ertugliflozin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Ertugliflozin; Sitagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Exenatide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Glimepiride: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Glipizide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Glipizide; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Glyburide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Glyburide; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Aspart: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Aspart; Insulin Aspart Protamine: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Degludec; Liraglutide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Detemir: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Glargine: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Glargine; Lixisenatide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Glulisine: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Lispro: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin Lispro; Insulin Lispro Protamine: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Insulin, Inhaled: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Isophane Insulin (NPH): (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Linagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Linagliptin; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Liraglutide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Lixisenatide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Metformin; Repaglinide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Metformin; Rosiglitazone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Metformin; Saxagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Metformin; Sitagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Miglitol: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Nateglinide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Pioglitazone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Pioglitazone; Glimepiride: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Pioglitazone; Metformin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Pramlintide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Either additive or antagonistic effects could potentially occur if prasterone is combined with progestins.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Either additive or antagonistic effects could potentially occur if prasterone is combined with progestins.
Regular Insulin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Regular Insulin; Isophane Insulin (NPH): (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Repaglinide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Rosiglitazone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Saxagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Semaglutide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Sitagliptin: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Tolazamide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Tolbutamide: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.

How Supplied

Hydroxyprogesterone Caproate/Makena Intramuscular Inj Sol: 1mL, 250mg
Makena Subcutaneous Inj Sol: 1mL, 250mg

Maximum Dosage
Adults

Dysfunctional uterine bleeding/amenorrhea: 375 mg/dose IM. For endometrial cancer: 1,000 mg/dose IM.

Geriatric

Dysfunctional uterine bleeding: 375 mg/dose IM. For endometrial cancer: 1,000 mg/dose IM.

Adolescents

Amenorrhea: 375 mg/dose IM.

Children

Safety and efficacy have not been established. Not indicated in children pre-menarche.

Infants

Not indicated.

Neonates

Not indicated.

Mechanism Of Action

Hydroxyprogesterone is a potent, long-acting, progestational steroid ester which transforms proliferative endothelium into secretory endothelium, induces mammary gland duct development, and inhibits the production and/or release of gonadotropic hormone; it also shows slight estrogenic, androgenic, or corticoid effects as well, but should not be relied upon for these effects. In advanced adenocarcinoma of the uterine corpus, hydroxyprogesterone caproate injection in a dosage of 1,000 mg or more, one or more times each week, often induces regressive changes.

Pharmacokinetics

Hydroxyprogesterone caproate is administered via intramuscular injection. Hydroxyprogesterone is extensively bound to plasma proteins including albumin and corticosteroid binding globulins. Hydroxyprogesterone is excreted in the urine and feces as both conjugated metabolites (predominantly) and free steroid. Hydroxyprogesterone caproate is metabolized by human hepatocytes, both by phase I and phase II reactions. The drug undergoes extensive reduction, hydroxylation, and conjugation. Conjugated metabolites include sulfated, glucuronidated, and acetylated products. During hydroxyprogesterone caproate metabolism, the caproate group is retained. In vitro data also indicate that metabolism occurs primarily via CYP3A4 and CYP3A5 isoenzymes.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP3A5
Hydroxyprogesterone appears to be metabolized by CYP3A4 and CYP3A5. It is possible that interactions with CYP3A enzyme inhibitors or inducers may occur. However, no drug-drug interaction studies have been performed in vivo in the treatment population of interest to discern clinical relevance of potential interactions.

Intramuscular Route

Following administration of a 250 mg IM dose of hydroxyprogesterone caproate, the elimination half-life of the parent compound and the mono-hydroxylated metabolites were 16. 4 (+/- 3.6) days and 19.7 (+/- 6.2) days, respectively. Following a single IM injection of hydroxyprogesterone caproate (1,000 mg), peak serum concentrations occurred after 3 to 7 days in non-pregnant female subjects. Mean maximal concentration (Cmax) was estimated to be 27.8 ng/mL and the mean time to maximum concentration (Tmax) was 4.6 days, respectively; the elimination half-life was 7.8 days. Once-weekly IM administration resulted in a trough concentration of 60 ng/mL after 13 weeks.

Subcutaneous Route

In a bioavailability study in 120 healthy post-menopausal women, comparable systemic exposure was seen when hydroxyprogesterone caproate was administered subcutaneously with an auto-injector (1.1 mL) in the back of the upper arm and when hydroxyprogesterone caproate was dosed intramuscularly (1 mL) in the upper outer quadrant of the gluteus maximus.

Pregnancy And Lactation
Pregnancy

Hydroxyprogesterone is not intended for use during pregnancy for preterm delivery prophylaxis as the required postmarketing study failed to verify clinical benefit in these patients. Data from the placebo-controlled clinical trial and the infant follow-up safety study did not show a difference in adverse developmental outcomes between children of hydroxyprogesterone-treated patients and the children of control subjects. However, these data are insufficient to determine a drug-associated risk of adverse developmental outcomes as none of the hydroxyprogesterone-treated individuals received the drug during the first trimester of pregnancy. In non-human primates, hydroxyprogesterone administration produced embryolethality in rhesus monkeys but not in cynomolgus monkeys exposed to 1 and 10 times the human dose equivalent every 7 days between days 20 and 146 of gestation. There were no teratogenic effects in either monkey species. Hydroxyprogesterone is contraindicated in patients with missed abortion and is contraindicated for use as a diagnostic test for pregnancy.

Hydroxyprogesterone is considered compatible with breast-feeding. Detectable amounts of progestins have been identified in the milk of lactating individuals receiving progestin treatment. Low levels of progestins are present in human milk with the use of progestin-containing products, including hydroxyprogesterone caproate. Published studies have reported no adverse effects of progestins on the breastfed child or on milk production.