Hydroxyprogesterone Caproate Injection

You should not use this medication if you are allergic to hydroxyprogesterone or castor oil, or if you have unusual vaginal bleeding, liver disease or liver cancer, breast cancer, uterine cancer, uncontrolled high blood pressure, a history of jaundice caused by pregnancy, or a history of stroke, blood clot, or circulation problems.

Before you receive hydroxyprogesterone, tell your doctor if you have eclampsia or preeclampsia, kidney disease, high blood pressure, heart disease, migraine headaches, a personal or family history of diabetes, asthma, seizures, depression, or fluid retention.

Your doctor will need to check your progress on a regular basis while you are using this medication. Do not miss any scheduled appointments. Every woman should remain under the care of a doctor during pregnancy.

Call your doctor at once if you have sudden numbness or weakness, confusion, problems with vision or speech, jaundice (yellowing of the skin or eyes), swelling in your hands or feet, pain or redness in one or both legs, or symptoms of depression (sleep problems, weakness, mood changes).

There are many other drugs that may interact with hydroxyprogesterone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products.

Do not start a new medication during pregnancy without telling your doctor.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

For the most serious adverse reactions to the use of progestins, see WARNINGS AND PRECAUTIONS.

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.1 [See Clinical Studies]

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 (Tables 1 and 2).

Table 1 : Selected Fetal Complications

Table 2 : Selected Maternal Complications

The most common adverse reaction was injection site pain, which was reported after at least one injection by 34.8% of the Makena group and 32.7% of the control group. Table 3 lists adverse reactions that occurred in ≥ 2% of subjects and at a higher rate in the Makena group than in the control group.

Table 3 : Adverse Reactions Occurring in ≥ 2% of Makena-Treated Subjects and at a Higher Rate than Control Subjects

In the clinical trial, 2.2% of subjects receiving Makena were reported as discontinuing therapy due to adverse reactions compared to 2.6% of control subjects. The most common adverse reactions that led to discontinuation in both groups were urticaria and injection site pain/swelling (1% each).

Pulmonary embolus in one subject and injection site cellulitis in another subject were reported as serious adverse reactions in Makena-treated subjects.

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

Read the entire FDA prescribing information for Makena (Hydroxyprogesterone Caproate Injection)

• It is used to treat some uterine cancers.
• It is used to treat abnormal period (menstrual) cycles.
• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Low mood (depression).
• Swelling in hands or feet.
• Very bad irritation where the shot was given.
• Swelling where hydroxyprogesterone caproate injection is used.
• Oozing of blood or fluid where the shot was given.
• Yellow skin or eyes.
• Vaginal bleeding that is not normal.
• Blood clots have happened with this medicine. Sometimes, these blood clots have been deadly. Call your doctor right away if you have chest, arm, back, neck, or jaw pain or pressure; coughing up blood; numbness or weakness on 1 side of your body, trouble speaking or thinking, change in balance, or change in eyesight; shortness of breath; or swelling, warmth, or pain in the leg or arm.
• For women, no period.
• A deep voice or more facial hair.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Pain where the shot was given.
• Irritation where the shot is given.
• Upset stomach or throwing up.
• Stomach cramps.
• Bloating.
• Breast soreness.
• Weight gain or loss.
• Headache.
• Hair loss.
• Lowered interest in sex.
• More interest in sex.
• Feeling more or less hungry.
• Dizziness.
• Feeling tired or weak.
• Back pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take hydroxyprogesterone caproate injection or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to hydroxyprogesterone caproate injection. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Hydroxyprogesterone Caproate Injection USP is a sterile, long-acting preparation of the caproate ester of the naturally-occurring progestational hormone, hydroxyprogesterone, in an oil solution for intramuscular use.

The chemical name for hydroxyprogesterone caproate is pregn-4-ene-3,20-dione, 17[(1-oxohexyl)oxy]. It has an empirical formula of C27H40O4 and a molecular weight of 428.60. Hydroxyprogesterone caproate exists as white to creamy white crystalline powder.

The structural formula is:

Each 5 mL multiple dose vial contains hydroxyprogesterone caproate, 250 mg/mL, in castor oil (28.6% v/v) and benzyl benzoate (46% v/v) with the preservative benzyl alcohol (2% v/v).

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.

Absorption: Peak serum levels of hydroxyprogesterone caproate appeared after 3 to 7 days in non-pregnant female subjects following a single intramuscular injection of 1,000 mg hydroxyprogesterone caproate. The pharmacokinetics of the 250 mg dose of hydroxyprogesterone caproate has not been evaluated in a study.

Metabolism: The conjugated metabolites include sulfated and glucuronidated products. In vitro data indicate that the metabolism of hydroxyprogesterone caproate is predominantly mediated by CYP3A4 and CYP3A5.

Excretion: Both conjugated metabolites and free steroids are excreted in the urine and feces, with the conjugated metabolites being prominent.

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of hydroxyprogesterone caproate has not been evaluated.

Hydroxyprogesterone caproate is extensively metabolized and hepatic impairment may reduce the elimination of hydroxyprogesterone caproate.

Renal Impairment

The effect of renal impairment on the pharmacokinetics of hydroxyprogesterone caproate has not been evaluated.