hydroxyprogesterone caproate (Rx)

Brand and Other Names:Makena
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Dosing & Uses

AdultPediatric

Dosing Form & Strengths

solution for IM injection

  • 250mg/mL (5mL multidose vial); in castor oil USP (28.6% v/v) and benzyl benzoate USP (46% v/v) with the preservative benzyl alcohol NF (2% v/v)
  • 250mg/mL (1mL single-dose vial); (25% w/v), in castor oil USP (30.6% v/v) and benzyl benzoate USP (46% v/v)

injection, solution for SC autoinjector

  • 275mg/1.1mL

FDA Proposes Withdrawal of Approval

October 5, 2020: The FDA is proposing hydroxyprogesterone caproate injection be withdrawn from the market as the required postmarket study following accelerated approval in 2011 failed to verify clinical benefit

For more information, see CDER proposes withdrawal of approval for Makena

Preterm Labor

Indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth

250 mg IM or 275 mg SC (using autoinjector for SC) q7days

Initiate between the 16th and 20th week of gestation; continue until the 37th week of gestation or delivery (whichever is first)

IM or SC injections must be administered by a healthcare professional

Also see Administration

Dosage Modifications

Renal impairment: Not studied in patients with renal impairment

Hepatic impairment: Not studied; product is extensively metabolized in liver; potential for reduce elimination

<16 years: Safety and efficacy not established

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Interactions

Interaction Checker

and hydroxyprogesterone caproate

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Injection site pain (34.8%)

            Injection site swelling (17.1%)

            Urticaria (12.3%)

            1-10%

            Pruritus (7.7%)

            Injection site pruritus (5.8%)

            Nausea (5.8%)

            Injection site nodule (4.5%)

            Diarrhea (2.3%)

            Frequency Not Defined

            Thromboembolic events

            Angioedema

            Depression

            Decreased glucose tolerance

            Fluid retention

            Jaundice

            Hypertension

            Vaginal bleeding

            Postmarketing Reports

            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

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            Warnings

            Contraindications

            Thromboembolism or history of thromboembolism

            Breast cancer or history of breast cancer

            Hormone sensitive cancer or history of hormone sensitive cancer

            Undiagnosed abnormal vaginal bleeding unrelated to pregnancy

            Cholestatic jaundice of pregnancy

            Liver tumors or active liver disease

            Uncontrolled hypertension

            Hypersensitivity to castor oil or hydroxyprogesterone caproate

            Cautions

            Not intended for use in women with multiple gestations or other risk factors for preterm birth

            Discontinue use if an arterial or deep venous thrombotic or thromboembolic event occurs

            Consider discontinuing if allergic reaction develops

            Monitor for the development of prediabetes, diabetes, or worsening diabetes

            Carefully monitor patients that have conditions sensitive to fluid retention (eg, preeclampsia, epilepsy, migraine, asthma, cardiac or renal dysfunction)

            Monitor women with history of depression and discontinue if depression recurs

            Carefully monitor women who develop jaundice and consider the risks and benefits of continuation

            Carefully monitor women who develop hypertension and consider the risks and benefits of continuation

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            Pregnancy & Lactation

            Pregnancy

            Indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth

            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 progesterone caproate-treated women and children of control subjects

            However, these data are insufficient to determine a drug-associated risk of adverse developmental outcomes as none of the treated women received the drug during the first trimester of pregnancy

            Animal data

            • In animal reproduction studies, IM administration to pregnant rats during gestation at doses 5 times the human dose equivalent based on a 60-kg human was not associated with adverse developmental outcomes

            Lactation

            Not indicated during time period when breastfeeding would occur

            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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Synthetic progestin

            Mechanism in risk reduction of preterm labor is unknown

            Absorption

            Note: Pharmacokinetic data based on single 1000 mg IM injection; data for 250 mg dose has not been evaluated

            Peak plasma concentration: 3-7 days (after a single IM injection)

            Peak plasma time: 4.6 (± 1.7) days

            Distribution

            Protein bound: binds extensively to plasma proteins (including albumin and corticosteroid binding globulins)

            Metabolism

            Half-life: 7.8 (± 3.0) days

            Metabolism: hepatic (primarily CYP3A4 and CYP3A5)

            Elimination

            Excretion: feces (50%), urine (30%); both conjugated and free drug

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            Administration

            IM Preparation

            Clean the vial top with alcohol swab before use

            Draw up 1 mL of drug (ie, 250 mg) into a 3 mL syringe using an 18-ga needle

            Change the needle to a 21-ga, 1.5-inch needle to administer the drug

            IM Administration

            Slow IM injection in upper outer quadrant of the gluteus maximus; rotate injection site to alternate side from previous week

            The solution is viscous and oily; slow injection (≥1 minute) is recommended

            1-mL vial does not contain preservatives and is for single dose use

            Once opened, the 5-mL multidose vial must be used within 5 weeks

            Discard any unused drug remaining in the opened vial after 5 weeks

            SC Administration

            Auto-injector is a single-use, prefilled, disposable device containing a 27-ga, 0.5-inch needle that delivers 1 SC dose sin the back of the upper arm

            Because the auto-injector is a preservative-free solution, once the cap is removed the device should be used immediately or discarded

            Rotate the injection site to the alternate arm from the previous week

            Do not use in areas where the skin is tender, bruised, red, scaly, raised, thick, or hard

            Avoid areas with scars, tattoos, or stretch marks

            The solution is viscous and oily; the auto-injector takes ~15 seconds to deliver the dose; when the viewing window is fully blocked (completely orange), the full dose has been administered

            See prescribing information for full instructions and diagrams

            Storage

            Store at controlled room temperature 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.