Drugs Details

Drugs Info of Makena, Prodrox
Drugs Details
  • Drugs Type  : FDA
  • Date : 6th Feb 2015 03:25 am
  • Brand Name : Makena, Prodrox
  • Generic Name :  hydroxyprogesterone (Pronunciation: hye DROX ee pro JES te rone)
Descriptions

The active pharmaceutical ingredient in Makena is hydroxyprogesterone caproate.

The chemical name for hydroxyprogesterone caproate is pregn-4-ene-3,20dione, 17[(1-oxohexyl)oxy]. It has an empirical formula of C27H40O4 and a molecular weight of 428.60. Hydroxyprogesterone caproate exists as white to practically white crystals or powder with a melting point of 120°-124°C. The structural formula is:

 

MAKENA® (hydroxyprogesterone caproate) Structural Formula Illustration

Makena is a clear, yellow, sterile, non-pyrogenic solution for intramuscular injection. Each 5 mL multidose vial contains hydroxyprogesterone caproate USP, 250 mg/mL (25% w/v), in castor oil USP (28.6% v/v) and benzyl benzoate USP (46% v/v) with the preservative benzyl alcohol NF (2% v/v).

What are the possible side effects of hydroxyprogesterone (Makena, Prodrox)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • sudden numbness or weakness, especially on one side of the body;
  • swelling, oozing, bleeding, or worsening pain where the injection was given;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • pain, swelling, warmth, or redness in one or both legs;
  • jaundice (yellowing...

Read All Potential Side Effects and See Pictures of Makena »

What are the precautions when taking hydroxyprogesterone caproate injection (Makena)?

Before using hydroxyprogesterone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, blood clots or other blood clotting problems, cancer (especially of the breast or other female organs), depression, diabetes, severe headaches/migraines, heart problems, high blood pressure, kidney problems, liver problems, seizure disorder, unusual vaginal bleeding, yellowing eyes/skin (jaundice) during pregnancy.

If you have diabetes, this medication may make it harder to control your blood sugar....

Read All Potential Precautions of Makena »


This monograph has been modified to include the generic and brand name in many instances.

Indications

Makena is a progestin indicated 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 Administration

Dosing

  • 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

Preparation and 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:

  1. Clean the vial top with an alcohol swab before use.
  2. Draw up 1 mL of drug into a 3 mL syringe with an 18 gauge needle.
  3. Change the needle to a 21 gauge 1½ inch needle.
  4. 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.
  5. Applying pressure to the injection site may minimize bruising and swelling.

Discard any unused product 5 weeks after first use.

How Supplied

Dosage Forms And Strengths

Makena (250 mg/mL) is a sterile solution of hydroxyprogesterone caproate in castor oil for injection. Each 5 mL multidose vial contains 1250 mg hydroxyprogesterone caproate.

Storage And Handling

Makena (NDC 64011-243-01) is supplied as 5 mL of a sterile solution in a multidose glass vial.

Each 5 mL vial contains hydroxyprogesterone caproate USP, 250 mg/mL (25% w/v), in castor oil USP (28.6% v/v) and benzyl benzoate USP (46% v/v) with the preservative benzyl alcohol NF (2% v/v).

Single unit carton: Contains one 5 mL multidose vial of Makena (250 mg/mL) containing 1250 mg of hydroxyprogesterone caproate.

Store at controlled room temperature [15°-30° C (59°-86° F)]. Use within 5 weeks after first use.

Caution: Protect vial from light. Store vial in its box. Store upright.

Manufactured by: Hospira, Inc. McPherson, KS 67460. Marketed by: Ther-Rx Corporation Chesterfield, MO 63005. Revised: 08/2013
This monograph has been modified to include the generic and brand name in many instances.

Side Effects

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

Pregnancy Complication Makena
n/N
Control
n/N
Miscarriage ( < 20 weeks)1 5/209 0/107
Stillbirth ( ≥ 20 weeks)2 6/305 2/153
1N = Total number of subjects enrolled prior to 20 weeks 0 days
2N = Total number of subjects at risk ≥ 20 weeks

Table 2 : Selected Maternal Complications

Pregnancy Complication Makena
N=310
%
Control
N=153
%
Admission for preterm labor1 16 13.8
Preeclampsia or gestational hypertension 8.8 4.6
Gestational diabetes 5.6 4.6
Oligohydramnios 3.6 1.3
1Other than delivery admission.
Common Adverse Reactions

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

Preferred Term Makena
N=310
%
Control
N=153
%
Injection site pain 34.8 32.7
Injection site swelling 17.1 7.8
Urticaria 12.3 11.1
Pruritus 7.7 5.9
Injection site pruritus 5.8 3.3
Nausea 5.8 4.6
Injection site nodule 4.5 2
Diarrhea 2.3 0.7

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 Makena (hydroxyprogesterone caproate injection) Side Effects Center for a complete guide to possible side effects

Interactions

In vitro drug-drug interaction studies were conducted with Makena. [See CLINICAL PHARMACOLOGY] No in vivo drug-drug interaction studies were conducted with Makena.

REFERENCES

1 Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379-85.

Read the Makena Drug Interactions Center for a complete guide to possible interactions

Learn More »


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

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.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION).

Counsel patients that Makena injections may cause pain, soreness, swelling, itching or bruising. Inform the patient to contact her physician if she notices increased discomfort over time, oozing of blood or fluid, or inflammatory reactions at the injection site [see ADVERSE REACTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Hydroxyprogesterone caproate has not been adequately evaluated for carcinogenicity.

No reproductive or developmental toxicity or impaired fertility was observed in a multigenerational study in rats. Makena administered intramuscularly, at gestational exposures up to 5 times the recommended human dose, had no adverse effects on the parental (F0) dams, their developing offspring (F1), or the latter offspring's ability to produce a viable, normal second (F2) generation.

Use In Specific Populations

Pregnancy

Pregnancy Category 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 infants2, 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.

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. [See Clinical Studies]

Geriatric Use

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

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.

REFERENCES

1 Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379-85.

2 Northen A, Norman G, Anderson K, et al. Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate. Obstet & Gynecol. 2007;110:865-872.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

There is no specific treatment for INLYTA overdose.

In a controlled clinical study with INLYTA for the treatment of patients with RCC, 1 patient inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).

In a clinical dose finding study with INLYTA, subjects who received starting doses of 10 mg twice daily or 20 mg twice daily experienced adverse reactions which included hypertension, seizures associated with hypertension, and fatal hemoptysis.

In cases of suspected overdose, INLYTA should be withheld and supportive care instituted.

ContrainDications

None


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

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

Pharmacodynamics

No specific pharmacodynamic studies were conducted with Makena (hydroxyprogesterone caproate injection) .

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.

Specific Populations

Renal Impairment: The effect of renal impairment on the pharmacokinetics of Makena (hydroxyprogesterone caproate injection) has not been evaluated.

Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of Makena (hydroxyprogesterone caproate injection) has not been evaluated.

Drug Interactions

Cytochrome P450 (CYP) enzymes: An in vitro study using human liver microsomes and CYP isoform-selective substrates indicated that hydroxyprogesterone caproate increased the metabolic rate of CYP1A2, CYP2A6, and CYP2B6 by approximately 80%, 150%, and 80%, respectively. The clinical implication of this in vitro metabolic acceleration is not well understood.

In vitro data indicated that therapeutic concentration of hydroxyprogesterone caproate is not likely to inhibit the activity of CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4.

The metabolic induction potential of hydroxyprogesterone caproate has not been evaluated.

Clinical Studies

Clinical Trial to Evaluate Reduction of Risk of Preterm Birth

In a multicenter, randomized, double-blind, vehicle (placebo)-controlled clinical trial, the safety and effectiveness of Makena (hydroxyprogesterone caproate injection) for the reduction of the risk of spontaneous preterm birth was studied in women with a singleton pregnancy (age 16 to 43 years) who had a documented history of singleton spontaneous preterm birth (defined as delivery at less than 37 weeks of gestation following spontaneous preterm labor or premature rupture of membranes).1 At the time of randomization (between 16 weeks, 0 days and 20 weeks, 6 days of gestation), an ultrasound examination had confirmed gestational age and no known fetal anomaly. Women were excluded for prior progesterone treatment or heparin therapy during the current pregnancy, a history of thromboembolic disease, or maternal/obstetrical complications (such as current or planned cerclage, hypertension requiring medication, or a seizure disorder).

A total of 463 pregnant women were randomized to receive either Makena (hydroxyprogesterone caproate injection) (N=310) or vehicle (N=153) at a dose of 250 mg administered weekly by intramuscular injection starting between 16 weeks, 0 days and 20 weeks, 6 days of gestation, and continuing until 37 weeks of gestation or delivery. Demographics of the Makena (hydroxyprogesterone caproate injection) -treated women were similar to those in the control group, and included: 59.0% Black, 25.5% Caucasian, 13.9% Hispanic and 0.6% Asian. The mean body mass index was 26.9 kg/m².

The proportions of women in each treatment arm who delivered at < 37 (the primary study endpoint), < 35, and < 32 weeks of gestation are displayed in Table 4.

Table 4 : Proportion of Subjects Delivering at < 37, < 35 and < 32 Weeks Gestational Age (ITT Population)

Delivery Outcome Makena (hydroxyprogesterone caproate injection) 1
(N=310)
%
Control
(N=153)
%
Treatment difference and 95% Confidence Interval2
< 37 weeks 37.1 54.9 -17.8% [-28.0%, -7.4%]
< 35 weeks 21.3 30.7 -9.4% [-19.0%, -0.4%]
< 32 weeks 11.9 19.6 -7.7% [-16.1%, -0.3%]
1 Four Makena (hydroxyprogesterone caproate injection) -treated subjects were lost to follow-up. They were counted as deliveries at their gestational ages at time of last contact (184, 220, 343 and 364 weeks).
2 Adjusted for interim analysis.

Compared to controls, treatment with Makena (hydroxyprogesterone caproate injection) reduced the proportion of women who delivered preterm at < 37 weeks. The proportions of women delivering at < 35 and < 32 weeks also were lower among women treated with Makena (hydroxyprogesterone caproate injection) . The upper bounds of the confidence intervals for the treatment difference at < 35 and < 32 weeks were close to zero. Inclusion of zero in a confidence interval would indicate the treatment difference is not statistically significant. Compared to the other gestational ages evaluated, the number of preterm births at < 32 weeks was limited.

After adjusting for time in the study, 7.5% of Makena (hydroxyprogesterone caproate injection) -treated subjects delivered prior to 25 weeks compared to 4.7% of control subjects; see Figure 1.

Figure 1 : Proportion of Women Remaining Pregnant as a Function of Gestational Age

View Enlarged Table

The rates of fetal losses and neonatal deaths in each treatment arm are displayed in Table 5. Due to the higher rate of miscarriages and stillbirths in the Makena (hydroxyprogesterone caproate injection) arm, there was no overall survival difference demonstrated in this clinical trial.

Table 5 : Fetal Losses and Neonatal Deaths

Complication Makena (hydroxyprogesterone caproate injection)
N=306A
n (%) B
Control
N=153
n (%) B
Miscarriages < 20 weeks gestation C 5 (2.4) 0
Stillbirth 6 (2.0) 2 (1.3)
  Antepartum stillbirth 5 (1.6) 1 (0.6)
  Intrapartum stillbirth 1 (0.3) 1 (0.6)
Neonatal deaths 8 (2.6) 9 (5.9)
Total Deaths 19 (6.2) 11 (7.2)
A Four of the 310 Makena (hydroxyprogesterone caproate injection) -treated subjects were lost to follow-up and stillbirth or neonatal status could not be determined
B Percentages are based on the number of enrolled subjects and not adjusted for time on drug
C Percentage adjusted for the number of at risk subjects (n=209 for Makena (hydroxyprogesterone caproate injection) , n=107 for control) enrolled at < 20 weeks gestation.

A composite neonatal morbidity/mortality index evaluated adverse outcomes in livebirths. It was based on the number of neonates who died or experienced respiratory distress syndrome, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, proven sepsis, or necrotizing enterocolitis. Although the proportion of neonates who experienced 1 or more events was numerically lower in the Makena (hydroxyprogesterone caproate injection) arm (11.9% vs. 17.2%), the number of adverse outcomes was limited and the difference between arms was not statistically significant.

Infant Follow-Up Safety Study

Infants born to women enrolled in this study, and who survived to be discharged from the nursery, were eligible for participation in a follow-up safety study. Of 348 eligible offspring, 79.9% enrolled: 194 children of Makena (hydroxyprogesterone caproate injection) -treated women and 84 children of control subjects. The primary endpoint was the score on the Ages & Stages Questionnaire (ASQ), which evaluates communication, gross motor, fine motor, problem solving, and personal/social parameters. The proportion of children whose scores met the screening threshold for developmental delay in each developmental domain was similar for each treatment group.2

REFERENCES

1 Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379-85.

2 Northen A, Norman G, Anderson K, et al. Follow-up of children exposed in utero to 17 alpha-hydroxyprogesterone caproate. Obstet & Gynecol. 2007;110:865-872.


This monograph has been modified to include the generic and brand name in many instances.

 

Patient Information

Makena
(mah-KEE-na)
(hydroxyprogesterone caproate) Injection 250 mg/mL

Read this Patient Information Leaflet before you receive Makena. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is Makena?

Makena is a prescription hormone medicine (progestin) used in women who are pregnant and who have delivered a baby too early (preterm) in the past. Makena is used in these women to help lower the risk of having a preterm baby again.

Makena is for women who:

  • Are pregnant with one baby
  • Have had a preterm delivery of one baby in the past

How well does Makena work?

Makena was studied in women who were at risk for having a preterm baby because they had previously given birth to a preterm baby. In the main study, about 37 of 100 women who received Makena gave birth preterm (before 37 weeks of pregnancy), compared to about 55 of 100 women who did not receive Makena. Another study of Makena is going on to see whether Makena reduces the number of babies who have serious problems shortly after birth or who die.

It is not known whether Makena is safe and effective in women who have other risk factors for preterm birth.

It is not known whether Makena is safe and effective in women less than 16 years old.

Makena is not intended for use to stop active preterm labor.

Who should not receive Makena?

Makena should not be used if you:

  • Have now or have had a history of blood clots or other blood clotting problems
  • Have now or have had a history of breast cancer or other hormone-sensitive cancers
  • Have unusual vaginal bleeding not related to your current pregnancy
  • Have yellowing of your skin due to liver problems during your pregnancy
  • Have liver problems, including liver tumors
  • Have uncontrolled high blood pressure

What should I tell my healthcare provider before receiving Makena?

Before you receive Makena, tell your healthcare provider if you have:

  • An allergy to hydroxyprogesterone caproate, castor oil, or any of the other ingredients in Makena. See the end of this patient leaflet for a complete list of the ingredients in Makena.
  • Diabetes or prediabetes
  • Epilepsy
  • Migraine headaches
  • Asthma
  • Heart problems
  • Kidney problems
  • Depression
  • High blood pressure

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Makena may affect the way other medicines work, and other medicines may affect how Makena works.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medication.

How should I receive Makena?

  • Do not give yourself Makena injections. A healthcare professional will give you the Makena injection into your hip area (upper outer area of the buttocks) once a week (every 7 days).
  • You will start receiving Makena injections anytime from 16 weeks and 0 days of your pregnancy up to 20 weeks and 6 days of your pregnancy.
  • You will continue to receive Makena injections once weekly until week 37 of your pregnancy or when your baby is delivered, whichever happens first.

Makena comes in ready-to-use vials. There are 5 doses of medicine in each vial. Your healthcare professional should give you only one dose (1 mL) of Makena as prescribed each week.

Makena should be used within 5 weeks after the first use.

It is very important that you do not miss a dose of Makena and that you continue to receive the medicine once a week. If you miss a dose, talk to your healthcare provider for specific directions on how to get back on schedule.

What are the possible side effects of Makena?

Makena may cause serious side effects, including:

  • Blood clots. Symptoms of a blood clot may include:
    • Leg swelling
    • Redness in your leg
    • A spot on your leg that is warm to touch
    • Leg pain that worsens when you bend your foot
  • Allergic reactions. Symptoms of an allergic reaction may include:
    • Hives
    • Itching
    • Swelling of the face

Call your healthcare provider right away if you get any of the symptoms above.

  • Depression
  • Yellowing of your skin and the whites of your eyes

The most common side effects of Makena include:

  • Pain, swelling, itching, bruising or a hard bump at the injection site
  • Hives
  • Itching
  • Nausea
  • Diarrhea

Call your healthcare provider if you have the following at your injection site:

  • Increased pain over time
  • Oozing of blood or fluid
  • Swelling

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Makena. For more information, ask your healthcare provider or pharmacist.

In a clinical study, certain complications or events associated with pregnancy occurred more often in women who received Makena compared to women who did not receive Makena, including:

  • Miscarriage (pregnancy loss before 20 weeks of pregnancy)
  • Stillbirth (fetal death occurring during or after the 20th week of pregnancy)
  • Hospital admission for preterm labor
  • Preeclampsia (high blood pressure and too much protein in your urine)
  • Gestational hypertension (high blood pressure caused by pregnancy)
  • Gestational diabetes
  • Oligohydramnios (low amniotic fluid levels)

Call your healthcare provider for medical advice about side effects or pregnancy complications. You may report side effects to FDA at 1-800-FDA1088.

How should I store Makena?

  • Store Makena at room temperature (59° to 86°F or 15° to 30°C)
  • Store Makena in the original box to protect it from light
  • Store the Makena box upright
  • Makena should be used within 5 weeks after the first use
  • Keep Makena out of the reach of children

General information about the safe and effective use of Makena

Medicines are sometimes prescribed for purposes other than those mentioned in the Patient Information Leaflets. Do not take Makena for conditions for which it was not prescribed. Do not give Makena to other people, even if they have the same condition you have. It may harm them.

This leaflet summarizes the most important information about Makena. If you would like more information, talk with your healthcare provider. You can ask for information about Makena that is written for healthcare professionals.

For more information, go to www.makena.com or call Ther-Rx Corporation Customer Service at the toll free number 1-877-567-7676.

To refill a prescription or to check on prescription status, call the Makena Care Connection at the toll free number 1-800-847-3418.

What are the ingredients in Makena?

Active ingredient: hydroxyprogesterone caproate

Inactive ingredients: castor oil, benzyl benzoate, and benzyl alcohol (a preservative)


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

HYDROXYPROGESTERONE - INTRAMUSCULAR

 

(hye-DROX-ee-proe-JES-ter-one)

 

COMMON BRAND NAME(S): Makena

 

USES: This medication is used in women who are pregnant with a single baby, and who have delivered a baby too early (preterm) in the past. It is used to help lower the risk of having a preterm baby again. Hydroxyprogesterone is a man-made form of a female hormone (progestin). It is not known how it works to prevent preterm labor.

This medication is not intended to prevent preterm birth in women pregnant with more than one baby (such as twins, triplets). It is also not intended to stop active preterm labor.

 

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using hydroxyprogesterone and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

This medication is given by injection into your hip area (upper outer area of the buttocks) by a health care professional, usually once a week (every 7 days) or as directed by your doctor. You will start receiving injections any time from 16 to 20 weeks of your pregnancy. You will continue to receive injections once a week until week 37 of your pregnancy or when your baby is delivered, whichever happens first.

Use this medication regularly to get the most benefit from it.

Consumer Overview Side Effect

SIDE EFFECTS: Pain, swelling, itching, bruising, or a lump at the injection site may occur. Nausea or diarrhea may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: dark urine, mental/mood changes (such as depression, nervousness), persistent nausea/vomiting, stomach/abdominal pain, unusual vaginal bleeding, yellowing eyes/skin.

This drug may rarely cause blood clots. Get medical help right away if any of these serious side effects occur: chest/jaw/left arm pain, confusion, pain/swelling/redness/warmth in the leg, slurred speech, sudden shortness of breath, sudden vision changes (such as partial/complete blindness), weakness on one side of the body.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Makena (hydroxyprogesterone caproate injection) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using hydroxyprogesterone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, blood clots or other blood clotting problems, cancer (especially of the breast or other female organs), depression, diabetes, severe headaches/migraines, heart problems, high blood pressure, kidney problems, liver problems, seizure disorder, unusual vaginal bleeding, yellowing eyes/skin (jaundice) during pregnancy.

If you have diabetes, this medication may make it harder to control your blood sugar. Check your blood sugar level regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high blood sugar, such as increased thirst and urination. Your doctor may need to adjust your diabetes medication or diet.

Tell your doctor if you will be having surgery or will be confined to a chair or bed for a long time (such as a long plane flight). You may need to take special precautions.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication is used to prevent preterm birth during pregnancy. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk. However, it is not used after 37 weeks of pregnancy, or after delivery. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Keep all regular medical and laboratory appointments.

 

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor immediately to establish a new dosing schedule.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

Information last revised November 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Makena, Prodrox

Generic Name: hydroxyprogesterone (Pronunciation: hye DROX ee pro JES te rone)

  • What is hydroxyprogesterone (Makena)?
  • What are the possible side effects of hydroxyprogesterone (Makena)?
  • What is the most important information I should know about hydroxyprogesterone (Makena)?
  • What should I discuss with my healthcare provider before receiving hydroxyprogesterone (Makena)?
  • How is hydroxyprogesterone given (Makena)?
  • What happens if I miss a dose (Makena)?
  • What happens if I overdose (Makena)?
  • What should I avoid while receiving hydroxyprogesterone (Makena)?
  • What other drugs will affect hydroxyprogesterone (Makena)?
  • Where can I get more information?

What is hydroxyprogesterone (Makena)?

Hydroxyprogesterone is a form of progestin, a manmade form of a female hormone called progesterone.

Hydroxyprogesterone is used to lower the risk of premature birth in a woman who has already had one premature baby. This medication will not stop premature labor that has already begun.

Hydroxyprogesterone is not for use in women who have had more than one pregnancy.

Hydroxyprogesterone may also be used for purposes not listed in this medication guide.

What are the possible side effects of hydroxyprogesterone (Makena)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • sudden numbness or weakness, especially on one side of the body;
  • swelling, oozing, bleeding, or worsening pain where the injection was given;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • pain, swelling, warmth, or redness in one or both legs;
  • jaundice (yellowing of the skin or eyes);
  • swelling in your hands, ankles, or feet; or
  • symptoms of depression (sleep problems, weakness, mood changes).

Less serious side effects may include:

  • mild itching;
  • nausea, diarrhea; or
  • pain, bruising, itching, swelling, or a hard lump where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Makena (hydroxyprogesterone caproate injection) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about hydroxyprogesterone (Makena)?

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.

Side Effects Centers
  • Makena

Patient Detailed How Take

What should I discuss with my healthcare provider before receiving hydroxyprogesterone (Makena)?

You should not receive this medication if you are allergic to hydroxyprogesterone or castor oil, or if you have:

  • unusual vaginal bleeding that has not been checked by a doctor;
  • liver disease or liver cancer;
  • a hormone related cancer such as breast or uterine cancer;
  • severe or uncontrolled high blood pressure;
  • a history of jaundice caused by pregnancy; or
  • a history of a stroke, blood clot, or circulation problems.

To make sure you can safely use hydroxyprogesterone, tell your doctor if you have any of these other conditions:

  • eclampsia or preeclampsia of pregnancy;
  • kidney disease;
  • high blood pressure, heart disease;
  • migraine headaches;
  • a personal or family history of diabetes;
  • asthma;
  • seizures;
  • depression; or
  • fluid retention.

Hydroxyprogesterone passes into breast milk, but it is not known whether this could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How is hydroxyprogesterone given (Makena)?

Hydroxyprogesterone is injected into a muscle. You will receive this injection in a clinic or doctor's office.

Hydroxyprogesterone is usually started during the 16th week of pregnancy and given once per week until the 37th week or until your baby is born. Follow your doctor's instructions.

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.

Side Effects Centers
  • Makena

Patient Detailed Avoid Taking

What happens if I miss a dose (Makena)?

Call your doctor for instructions if you miss an appointment for your hydroxyprogesterone injection.

What happens if I overdose (Makena)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving hydroxyprogesterone (Makena)?

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

What other drugs will affect hydroxyprogesterone (Makena)?

Tell your doctor about all other medicines you use, especially:

  • acetaminophen (Tylenol);
  • alosetron (Lotronex);
  • betaxolol (Kerlone) or propranolol (Inderal, InnoPran);
  • cyclophosphamide (Gengraf, Neoral, Sandimmune);
  • efavirenz (Sustiva, Atripla);
  • methadone (Methadose, Diskets, Dolophine);
  • mexiletine (Mexitil);
  • nicotine (Nicorette, Commit, Habitrol, Nicotrol, Nicoderm);
  • rifabutin (Mycobutin) or rifampin (Rifater, Rifadin, Rifamate);
  • riluzole (Rilutek);
  • ropinirole (Requip);
  • selegiline (Eldepryl, Emsam, Zelapar);
  • tacrine (Cognex);
  • an antidepressant such as bupropion (Wellbutrin), clomipramine (Anafranil), doxepin (Adapin, Sinequan), duloxetine (Cymbalta), fluvoxamine (Luvox), or mirtazepine (Remeron),
  • asthma medication such as aminophylline (Phyllocontin, Truphylline) or theophylline (Elixophyllin, Theo-24, Theochron, Uniphyl);
  • cancer medicine such as dacarbazine (DTIC-Dome), flutamide (Eulexin), or irinotecan (Camptosar);
  • medicines to treat psychiatric disorders, such as clozapine (Clozaril, FazaClo), pimozide (Orap), promethazine (Phenergan), thiothixene (Navane), or trifluoperazine (Stelazine); or
  • a muscle relaxer such as cyclobenzaprine (Flexeril) or tizanidine (Zanaflex).

This list is not complete and other drugs 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 without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about hydroxyprogesterone.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.01. Revision date: 8/26/2011.

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