Hydroxyprogesterone Case

Hydroxyprogesterone

Judy Ankney

University of Cincinnati

Pharmacology for Advanced Nurse Practitioners

May 26, 2011

Brand names: Makena

Generic name: Hydroxyprogesterone Caproate (17P)

Therapeutic Category: Synthetic steroid hormone (Katzung, 2009)

Classification: Hormones-Progestin

How Supplied: Hydroxyprogesterone Caproate Solution for Injection

250mg/ml Solution for Injection (in castor oil)

Legal prescriptive considerations: Hydroxyprogesterone caproate is a nonscheduled prescriptive drug.

Pregnancy Category: Category B (Medscape Drugs & Procedures, 2011)

Breast Feeding: Excreted into breast milk, probably safe. There is limited information in animals and /or humans demonstrate no risk/minimal risk of adverse effects to infant/breast milk production, caution advised (Medscape Drugs & Procedures, 2011).

Metabolism: Liver extensively (Medscape Drugs & Procedures, 2011).

Excretion: Feces 50%, Urine 30%, Half-life: 7.8 days Peak plasma concentration: 3-7 days (after single IM injection). Peak plasma time: 4.6 days (Medscape Drugs & Procedures, 2011).

Sound Alike Look Alike Drugs: None

Mechanism of Action: Hydroxyprogesterone caproate (17P) is a synthetic progestin. The mechanism by which Hydroxyprogesterone caproate reduces the risk of recurrent preterm birth is not known, part of this is due to the fact that preterm labor is not fully understood. (Ther-Rx Corporation, 2011). Progesterone is felt to be an important hormone in maintaining pregnancy early in gestation as well as later in pregnancy. Progesterone supplementation has been investigated based on several mechanisms of action, including reduced gap junction formation and oxytocin antagonism leading to relaxation of smooth muscle, maintenance of cervical integrity, and anti-inflammatory effects (Creasy & Resniks, 2009). It has been shown in animals and humans that a drop in progesterone concentrations and an increase in estrogen concentrations occur before labor begins.

Pharmacokinetics: The pharmacokinetics of the 250mg IM dose of Hydroxyprogesterone caproate has not been evaluated. Following a single IM injection of Hydroxyprogesterone caproate (1000mg), peak serum concentrations occurred after 3-7 days in non-pregnant female subjects following a single intramuscular injection of 1000mg of 17P. The elimination half-life of Hydroxyprogesterone caproate was 7.8 (+/- 3.0) days. Once weekly IM administration resulted in trough concentration of 60 ng/ml after 13 weeks (Clinical Pharmacology, 2011).

Indications: Hydroxyprogesterone Caproate is a progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy that has a history of singleton spontaneous preterm birth. Other indications include: amenorrhea, dysfunctional uterine bleeding, endometrial cancer, and test for endogenous estrogen production (Clinical Pharmacology, 2011).

Adult Dosing: Dosage form: Intramuscular (IM) Injection. Preterm birth risk reduction: 250mg (1 ml) IM every week starting at 16 weeks 0 days up to 20 weeks and 6 days of pregnancy. Continue once weekly until 36 weeks 6 days gestation or delivery, whichever occurs first (Ther-Rx Corporation, 2011). Treatment of amenorrhea and dysfunctional uterine bleeding: Adult female intramuscular dosage is 375mg IM. May be repeated at 4-week intervals as needed. Treatment of endometrial cancer: Adult female intramuscular dosage is 1000mg IM up to seven times per week for 12 weeks. To test for endogenous estrogen production: Adult female intramuscular dosage 250 mg IM once, then repeat for confirmation at 4 weeks. Bleeding should occur 7-14 days after the injection. Renal dosing and hepatic dosing has not been defined. Hepatic impairment may reduce elimination of the drug, caution advised (Medscape Drugs & Procedures, 2011)

Pediatric Dosing: Dosage form: Intramuscular (IM) Injection. There is no data in children younger than 16 years old. Responses to 16 years old and greater are expected to be similar to adults. Preterm birth risk reduction: > 16 years old. 250mg IM every week starting at 16-20 weeks gestation and continuing until 36 weeks 6 days gestation. Renal dosing and hepatic dosing has not been defined. Hepatic impairment may reduce elimination of the drug, caution advised (Medscape Drugs & Procedures, 2011).

Dosage Forms and Strength: Makena (250mg/ml is a sterile solution of Hydroxyprogesterone caproate in castor oil for injection. Each 5 ml multi-dose vial contains 1250 mg of Hydroxyprogesterone caproate. If patient has hypersensitivity to castor oil Hydroxyprogesterone can be mixed with sesame oil (Ther-Rx Corporation, 2011).

Contraindications: Do not use Hydroxyprogesterone