Makena (DSC)

Drug Overview

In the field of Gynecology and Obstetrics, preventing preterm birth has long been one of the most critical challenges for ensuring the health of both mother and baby. Makena, which belongs to the Progestin Hormone drug class, was widely used for over a decade as a specialized treatment to help high-risk pregnant women carry their babies closer to full term.

Please note that Makena carries the “DSC” (Discontinued) designation. In April 2023, the U.S. Food and Drug Administration (FDA) officially withdrew the approval for Makena and its generic equivalents. It is no longer available on the market, but understanding its history and how it worked remains important for patients and healthcare professionals discussing past treatments and future alternatives.

• Generic Name: Hydroxyprogesterone caproate (often abbreviated as 17-OHPC)
• US Brand Names: Makena (DSC)
• Route of Administration: Intramuscular (IM) injection or Subcutaneous (under the skin) injection via an auto-injector.
• FDA Approval Status: Originally granted accelerated approval in 2011; FDA approval was officially withdrawn in April 2023 due to post-market studies failing to verify its clinical benefit.
  
  Discover detailed information on Makena (DSC). As a Progestin Hormone, it is prescribed for Reduction of preterm birth risk. Contact our specialists.

What Is It and How Does It Work? (Mechanism of Action)

Makena is a synthetic (man-made) version of progesterone, which is often called the “hormone of pregnancy.” Naturally produced by the ovaries and the placenta, progesterone is essential for keeping the uterus relaxed and supporting the growth of the fetus.

As a Hormone Modulator, Makena was designed to act as a Targeted Therapy to support the female reproductive system during a high-risk pregnancy. At the molecular and hormonal level, its mechanism of action involved:

1. Receptor Agonism: Hydroxyprogesterone caproate binds directly to progesterone receptors located in the myometrium (the muscular wall of the uterus).
2. Muscle Relaxation: By activating these receptors, the medication helps block the pathways that cause the uterine muscles to contract. It essentially keeps the uterus in a state of calm, resting tension.
3. Inflammation Suppression: Preterm labor is often triggered by an inflammatory response that causes the cervix to soften and open too early. This progestin acts to inhibit the release of inflammatory enzymes and prostaglandins, thereby keeping the cervix long and closed.
4. Hormonal Support: It provides a steady, long-lasting reservoir of progestin to supplement the body’s natural hormones, acting as a chemical “quieting” signal to the reproductive tract.

FDA-Approved Clinical Indications

Note: Because Makena is discontinued, these represent its historical indications prior to withdrawal.

Primary Indication

• Reduction of Preterm Birth Risk: Makena was specifically indicated to lower the risk of preterm birth in women pregnant with a single baby (singleton pregnancy) who had a history of a previous spontaneous preterm birth.

Other Approved & Off-Label Uses

While Makena was tightly regulated for its specific obstetric use, the generic active ingredient (hydroxyprogesterone caproate) was sometimes used historically in other areas of women’s health:

• Primary Gynecological/Obstetric Indications
  • Prevention of recurrent spontaneous preterm birth (historical primary use).
• Off-Label / Endocrinological Indications
  • Historically used for the treatment of certain menstrual disorders, such as primary amenorrhea (lack of periods) or abnormal uterine bleeding (though oral progestins are the modern standard of care).
  • Historically used as part of luteal phase hormone support.

Dosage and Administration Protocols

When Makena was actively prescribed, it required a strict and continuous dosing schedule administered by a healthcare professional or a trained caregiver.

Specific Adjustments and Considerations:

• Hepatic (Liver) Insufficiency: The drug was contraindicated (not allowed) in women with liver tumors or active liver disease, as the liver is responsible for breaking down the hormone.
• Multiples: Makena was not effective and not approved for women carrying twins, triplets, or more.

Clinical Efficacy and Research Results

The clinical journey of Makena highlights the importance of ongoing medical research. Its initial 2011 FDA approval was based on a 2003 trial (the Meis trial), which showed that women receiving the drug had a roughly 34% reduction in the rate of preterm birth before 37 weeks compared to those taking a placebo.

However, recent clinical study data (including the major PROLONG trial, which heavily influenced the 2020-2023 FDA reviews) failed to confirm these benefits.

• Preterm Birth Rates: The confirmatory trial showed no statistically significant difference in preterm birth rates before 35 weeks (approximately 11% in the Makena group versus 11.5% in the placebo group).
• Neonatal Outcomes: The trial also showed no significant improvement in newborn health outcomes, such as reduced rates of neonatal respiratory distress or time spent in the neonatal intensive care unit (NICU).
  Because the modern, larger-scale data did not prove that Makena prevented preterm birth or improved baby outcomes, the FDA concluded the drug was no longer justified for the market, leading to its discontinuation.

Safety Profile and Side Effects

Common Side Effects (>10%)

• Injection site reactions (pain, swelling, itching, or a hard lump where the shot was given).
• Nausea and mild diarrhea.
• Fatigue.

Serious Adverse Events

• VTE/Thrombosis Risk: An increased risk of dangerous blood clots (thromboembolism), including deep vein thrombosis (DVT) in the legs or pulmonary embolism (PE) in the lungs.
• Depression: New or worsening clinical depression.
• Jaundice: Yellowing of the skin or eyes due to liver stress.
• Allergic Reactions: Severe allergic responses, including hives and trouble breathing.

Management Strategies

When patients experienced injection site pain, applying a cold pack for a few minutes before the shot and a warm compress afterward was often recommended. If a patient developed symptoms of a blood clot (such as sudden, severe leg pain, chest pain, or shortness of breath) or severe depression, the medication was stopped immediately, and emergency medical intervention was required.

Research Areas

With the discontinuation of Makena, the medical community is actively seeking new ways to prevent preterm birth. Current research in Gynecology and Obstetrics is focusing on alternatives to systemic Hormone Modulator injections. Scientists are exploring targeted drug delivery systems in women’s health, such as localized vaginal progesterone, which delivers the hormone directly to the cervix with fewer full-body side effects. Additionally, researchers are studying the vaginal microbiome, looking at how adjusting healthy bacteria might prevent the infections and inflammation that trigger early labor. While stem cell therapies are not yet a standard for preventing preterm birth, regenerative medicine is heavily researching how to repair weakened cervical tissue (cervical insufficiency) before pregnancy even begins.

Patient Management and Practical Recommendations

For women who have a history of preterm birth, modern patient management relies on vigilant monitoring and alternative therapies.

Pre-treatment Tests to be Performed

• Pelvic Ultrasound: To accurately date the pregnancy and routinely measure cervical length. A shortening cervix is a primary warning sign of early labor.
• Fetal Fibronectin Test: A swab test that can help predict the likelihood of going into early labor within the next two weeks.
• Baseline Blood Pressure and Glucose: To monitor for other pregnancy complications like preeclampsia or gestational diabetes.

Precautions During Treatment (and Modern Alternatives)

• Symptom Vigilance: High-risk pregnant women must be hyper-aware of early labor signs, such as pelvic pressure, low dull backache, regular cramps, or a change in vaginal discharge.
• Lifestyle Adjustments: While strict bed rest is rarely recommended anymore, patients may be advised to reduce heavy physical exertion and stay highly hydrated to prevent uterine irritability.

“Do’s and Don’ts” List

• DO attend all of your high-risk prenatal appointments, including regular cervical length ultrasounds.
• DO ask your obstetrician about alternative treatments like vaginal progesterone or a cervical cerclage (a stitch to keep the cervix closed) if you have a history of preterm birth.
• DON’T ignore mild cramping or backaches; always call your healthcare provider to be safe.
• DON’T look for Makena online or through unverified pharmacies, as it is no longer an FDA-approved or legally distributed medication.

Legal Disclaimer

The medical information provided in this guide is for informational purposes only and does not replace professional medical advice, diagnosis, or treatment from a qualified healthcare provider. Makena (hydroxyprogesterone caproate) has been discontinued by the FDA and is no longer available. Always consult your obstetrician or maternal-fetal medicine specialist to discuss currently approved and safe options for managing a high-risk pregnancy. In the event of a medical emergency, such as signs of early labor, seek immediate assistance from emergency services.