Hydroxyprogesterone caproate: Difference between revisions

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Makena 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 species.
Makena 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 species.
|useInLaborDelivery=Makena is not intended for use to stop active preterm labor. The effect of Makena in active labor is unknown.
|useInNursing=Discontinue Makena at 37 weeks of gestation or upon delivery. Detectable amounts of progestins have been identified in the milk of mothers receiving progestin treatment. Many studies have found no adverse effects of progestins on breastfeeding performance, or on the health, growth, or development of the infant
|useInPed=Makena is not indicated for use in children. Safety and effectiveness in pediatric patients less than 16 years of age have not been established. A small number of women under age 18 years were studied; safety and efficacy are expected to be the same in women aged 16 years and above as for users 18 years and older.
|useInGeri=Makena is not intended for use in postmenopausal women. Safety and effectiveness in postmenopausal women have not been established.
|useInRenalImpair=No studies have been conducted to examine the pharmacokinetics of Makena in patients with renal impairment.
|useInHepaticImpair=No studies have been conducted to examine the pharmacokinetics of Makena in patients with hepatic impairment. Makena is extensively metabolized and hepatic impairment may reduce the elimination of Makena.
|administration=Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Makena is a clear, yellow solution. Do not use if solid particles appear or if the solution is cloudy.
|administration=Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Makena is a clear, yellow solution. Do not use if solid particles appear or if the solution is cloudy.



Revision as of 18:09, 12 March 2015

Hydroxyprogesterone caproate
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anusha Vege, M.B.B.S. [2]

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Overview

Hydroxyprogesterone caproate is a progestin that is FDA approved for the treatment of indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.. Common adverse reactions include injection site reactions (pain [35%], swelling [17%], pruritus [6%], nodule [5%]), urticaria (12%), pruritus (8%), nausea (6%), and diarrhea (2%)..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Used to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The effectiveness of Makena is based on improvement in the proportion of women who delivered <37 weeks of gestation. There are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.

Limitation of use: While there are many risk factors for preterm birth, safety and efficacy of Makena has been demonstrated only in women with a prior spontaneous singleton preterm birth. It is not intended for use in women with multiple gestations or other risk factors for preterm birth.

Dosage

Administer intramuscularly at a dose of 250 mg (1 mL) once weekly (every 7 days) by a healthcare provider Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation Continue administration once weekly until week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever occurs first.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Hydroxyprogesterone caproate in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Hydroxyprogesterone caproate in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Hydroxyprogesterone caproate FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Hydroxyprogesterone caproate in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Hydroxyprogesterone caproate in pediatric patients.

Contraindications

Current or history of thrombosis or thromboembolic disorders

  • Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions
  • Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
  • Cholestatic jaundice of pregnancy
  • Liver tumors, benign or malignant, or active liver disease
  • Uncontrolled hypertension

Warnings

Thromboembolic Disorders

Discontinue Makena if an arterial or deep venous thrombotic or thromboembolic event occurs.

Allergic Reactions

Allergic reactions, including urticaria, pruritus and angioedema, have been reported with use of Makena or with other products containing castor oil. Consider discontinuing the drug if such reactions occur.

Decrease in Glucose Tolerance

A decrease in glucose tolerance has been observed in some patients on progestin treatment. The mechanism of this decrease is not known. Carefully monitor prediabetic and diabetic women while they are receiving Makena.

Fluid Retention

Because progestational drugs may cause some degree of fluid retention, carefully monitor women with conditions that might be influenced by this effect (e.g., preeclampsia, epilepsy, migraine, asthma, cardiac or renal dysfunction).

Depression

Monitor women who have a history of clinical depression and discontinue Makena if clinical depression recurs.

Jaundice

Carefully monitor women who develop jaundice while receiving Makena and consider whether the benefit of use warrants continuation.

Hypertension

Carefully monitor women who develop hypertension while receiving Makena and consider whether the benefit of use warrants continuation.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a vehicle (placebo)-controlled clinical trial of 463 pregnant women at risk for spontaneous preterm delivery based on obstetrical history, 310 received 250 mg of Makena and 153 received a vehicle formulation containing no drug by a weekly intramuscular injection beginning at 16 to 20 weeks of gestation and continuing until 37 weeks of gestation or delivery, whichever occurred first.

Certain pregnancy-related fetal and maternal complications or events were numerically increased in the Makena-treated subjects as compared to control subjects, including miscarriage and stillbirth, admission for preterm labor, preeclampsia or gestational hypertension, gestational diabetes, and oligohydramnios.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Makena. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Body as a whole: Local injection site reactions (including erythema, urticaria, rash, irritation, hypersensitivity, warmth); fatigue; fever; hot flashes/flushes
  • Digestive disorders: Vomiting
  • Infections: Urinary tract infection
  • Nervous system disorders: Headache, dizziness
  • Pregnancy, puerperium and perinatal conditions: Cervical incompetence, premature rupture of membranes
  • Reproductive system and breast disorders: Cervical dilation, shortened cervix
  • Respiratory disorders: Dyspnea, chest discomfort
  • Skin: Rash

Drug Interactions

There is limited information regarding Hydroxyprogesterone caproate Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B There are no adequate and well-controlled studies of Makena use in women during the first trimester of pregnancy. Data from a vehicle (placebo)-controlled clinical trial of 310 pregnant women who received Makena at weekly doses of 250 mg by intramuscular injection in their second and third trimesters1, as well as long-term (2-5 years) follow-up safety data on 194 of their infants 2, did not demonstrate any teratogenic risks to infants from in utero exposure to Makena.

Reproduction studies have been performed in mice and rats at doses up to 95 and 5, respectively, times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Makena.

Makena 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 species.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Hydroxyprogesterone caproate in women who are pregnant.

Labor and Delivery

Makena is not intended for use to stop active preterm labor. The effect of Makena in active labor is unknown.

Nursing Mothers

Discontinue Makena at 37 weeks of gestation or upon delivery. Detectable amounts of progestins have been identified in the milk of mothers receiving progestin treatment. Many studies have found no adverse effects of progestins on breastfeeding performance, or on the health, growth, or development of the infant

Pediatric Use

Makena is not indicated for use in children. Safety and effectiveness in pediatric patients less than 16 years of age have not been established. A small number of women under age 18 years were studied; safety and efficacy are expected to be the same in women aged 16 years and above as for users 18 years and older.

Geriatic Use

Makena is not intended for use in postmenopausal women. Safety and effectiveness in postmenopausal women have not been established.

Gender

There is no FDA guidance on the use of Hydroxyprogesterone caproate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Hydroxyprogesterone caproate with respect to specific racial populations.

Renal Impairment

No studies have been conducted to examine the pharmacokinetics of Makena in patients with renal impairment.

Hepatic Impairment

No studies have been conducted to examine the pharmacokinetics of Makena in patients with hepatic impairment. Makena is extensively metabolized and hepatic impairment may reduce the elimination of Makena.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Hydroxyprogesterone caproate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Hydroxyprogesterone caproate in patients who are immunocompromised.

Administration and Monitoring

Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Makena is a clear, yellow solution. Do not use if solid particles appear or if the solution is cloudy.

Instructions for administration

Clean the vial top with an alcohol swab before use. Draw up 1 mL of drug into a 3 mL syringe with an 18 gauge needle. Change the needle to a 21 gauge 1 1/2 inch needle. After preparing the skin, inject in the upper outer quadrant of the gluteus maximus. The solution is viscous and oily. Slow injection (over one minute or longer) is recommended. Applying pressure to the injection site may minimize bruising and swelling. Discard any unused product 5 weeks after first use.

Monitoring

There is limited information regarding Hydroxyprogesterone caproate Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Hydroxyprogesterone caproate and IV administrations.

Overdosage

There is limited information regarding Hydroxyprogesterone caproate overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Hydroxyprogesterone caproate Pharmacology in the drug label.

Mechanism of Action

Hydroxyprogesterone caproate is a synthetic progestin. The mechanism by which hydroxyprogesterone caproate reduces the risk recurrent preterm birth is not known.

Structure

There is limited information regarding Hydroxyprogesterone caproate Structure in the drug label.

Pharmacodynamics

No specific pharmacodynamic studies were conducted with Makena.

Pharmacokinetics

Absorption: Peak serum levels of hydroxyprogesterone caproate appeared after 3-7 days in non-pregnant female subjects following a single intramuscular injection of 1000 mg hydroxyprogesterone caproate. Based on pharmacokinetic analysis of five non-pregnant female subjects who received a single intramuscular administration of 1000 mg hydroxyprogesterone caproate, the mean (±SD) Cmax is estimated to be 27.8 (±5.3) ng/mL, and the Tmax is estimated to be 4.6 (±1.7) days. The elimination half-life of hydroxyprogesterone caproate was 7.8 (±3.0) days. Once-weekly intramuscular administration of 1000 mg hydroxyprogesterone caproate to non-pregnant women resulted in trough concentration of 60.0 (±14) ng/mL after 13 weeks. The pharmacokinetics of the 250 mg dose of hydroxyprogesterone caproate has not been evaluated.

Distribution: Hydroxyprogesterone caproate binds extensively to plasma proteins including albumin and corticosteroid binding globulins.

Metabolism: In vitro studies have shown that hydroxyprogesterone caproate can be metabolized by human hepatocytes, both by phase I and phase II reactions. Hydroxyprogesterone caproate undergoes extensive reduction, hydroxylation and conjugation. The conjugated metabolites include sulfated, glucuronidated and acetylated products. In vitro data indicate that the metabolism of hydroxyprogesterone caproate is predominantly mediated by CYP3A4 and CYP3A5. The in vitro data indicate that the caproate group is retained during metabolism of hydroxyprogesterone caproate.

Excretion: Both conjugated metabolites and free steroids are excreted in the urine and feces, with the conjugated metabolites being prominent. Following intramuscular administration to pregnant women at 10-12 weeks gestation, approximately 50% of a dose was recovered in the feces and approximately 30% recovered in the urine.

Nonclinical Toxicology

There is limited information regarding Hydroxyprogesterone caproate Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Hydroxyprogesterone caproate Clinical Studies in the drug label.

How Supplied

There is limited information regarding Hydroxyprogesterone caproate How Supplied in the drug label.

Storage

There is limited information regarding Hydroxyprogesterone caproate Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Hydroxyprogesterone caproate Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Hydroxyprogesterone caproate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Hydroxyprogesterone caproate Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Hydroxyprogesterone caproate Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.