Primolut Depot

Primolut Depot uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• References
• How supplied/storage and handling
• Patient counseling information
• Primolut Depot reviews

1 INDICATIONS AND USAGE

Primolut Depot 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 Primolut Depot 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 Primolut Depot 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.

Primolut Depot 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.

Limitation of use: Primolut Depot is not intended for use in women with multiple gestations or other risk factors for preterm birth. (1)

2 DOSAGE AND ADMINISTRATION

• Administer intramuscularly at a dose of 250 mg once weekly
• 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 (2.1)

2.1 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

2.2 Preparation and Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Primolut Depot is a clear, yellow solution. Do not store for long periods of time at low temperatures as this may cause the solution to appear cloudy due to crystallization. The solution must be clear at the time of use, replace vial if visible particles are present. Do not refrigerate.

Instructions for administration:

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

If the 5 mL multidose vial is used, discard any unused product 5 weeks after first use.

3 DOSAGE FORMS AND STRENGTHS

Primolut Depot (250 mg/mL) is a sterile solution of hydroxyprogesterone caproate in castor oil for injection. Each 1 mL single dose vial contains 250 mg Primolut Depot. Each 5 mL multidose vial contains 1250 mg Primolut Depot.

1 mL single dose vial contains 250 mg of Primolut Depot.

5 mL multidose vial (250 mg/mL) contains 1250 mg Primolut Depot. (3)

4 CONTRAINDICATIONS

Do not use Primolut Depot in women with any of the following conditions:

• Current or history of thrombosis or thromboembolic disorders
• Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions
• Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
• Cholestatic jaundice of pregnancy
• Liver tumors, benign or malignant, or active liver disease
• Uncontrolled hypertension

• Current or history of thrombosis or thromboembolic disorders (4)
• Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions (4)
• Undiagnosed abnormal vaginal bleeding unrelated to pregnancy (4)
• Cholestatic jaundice of pregnancy (4)
• Liver tumors, benign or malignant, or active liver disease (4)
• Uncontrolled hypertension (4)

5 WARNINGS AND PRECAUTIONS

• Thromboembolic disorders: Discontinue if thrombosis or thromboembolism occurs
• Allergic reactions: Consider discontinuing if allergic reactions occur (5.2)
• Decreased glucose tolerance: Monitor prediabetic and diabetic women receiving Primolut Depot (5.3)
• Fluid retention: Monitor women with conditions that may be affected by fluid retention, such as preeclampsia, epilepsy, cardiac or renal dysfunction (5.4)
• Depression: Monitor women with a history of clinical depression; discontinue Primolut Depot if depression recurs (5.5)

5.1 Thromboembolic Disorders

Discontinue Primolut Depot if an arterial or deep venous thrombotic or thromboembolic event occurs.

5.2 Allergic Reactions

Allergic reactions, including urticaria, pruritus and angioedema, have been reported with use of Primolut Depot or with other products containing castor oil. Consider discontinuing the drug if such reactions occur.

5.3 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 Primolut Depot.

5.4 Fluid Retention

Because progestational drugs may cause some degree of fluid retention, carefully monitor women with conditions that might be influenced by this effect.

5.5 Depression

Monitor women who have a history of clinical depression and discontinue Primolut Depot if clinical depression recurs.

5.6 Jaundice

Carefully monitor women who develop jaundice while receiving Primolut Depot and consider whether the benefit of use warrants continuation.

5.7 Hypertension

Carefully monitor women who develop hypertension while receiving Primolut Depot and consider whether the benefit of use warrants continuation.

6 ADVERSE REACTIONS

For the most serious adverse reactions to the use of progestins, see Warnings and Precautions.

Most common adverse reactions reported in ≥ 2% of subjects and at a higher rate in the Primolut Depot group than in the control group are injection site reactions (pain [35%], swelling [17%], pruritus [6%], nodule [5%]), urticaria (12%), pruritus (8%), nausea (6%), and diarrhea (2%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact AMAG Pharmaceuticals at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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 Primolut Depot 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

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).

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 Primolut Depot 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 Primolut Depot group than in the control group.

In the clinical trial, 2.2% of subjects receiving Primolut Depot 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.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Primolut Depot. 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

7 DRUG INTERACTIONS

In vitro drug-drug interaction studies were conducted with Primolut Depot. No in vivo drug-drug interaction studies were conducted with Primolut Depot.

8 USE IN SPECIFIC POPULATIONS

Pregnancy: Controlled studies show no increase in congenital anomalies, including genital abnormalities in male or female infants, from exposure during pregnancy to Primolut Depot.

8.1 Pregnancy

Pregnancy Category B: There are no adequate and well-controlled studies of Primolut Depot use in women during the first trimester of pregnancy. Data from a vehicle (placebo)-controlled clinical trial of 310 pregnant women who received Primolut Depot 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 infants ², did not demonstrate any teratogenic risks to infants from in utero exposure to Primolut Depot.

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 Primolut Depot.

Primolut Depot 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.

8.2 Labor and Delivery

Primolut Depot is not intended for use to stop active preterm labor. The effect of Primolut Depot in active labor is unknown.

8.3 Nursing Mothers

Discontinue Primolut Depot 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.

8.4 Pediatric Use

Primolut Depot 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.

8.5 Geriatric Use

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

8.6 Renal Impairment

No studies have been conducted to examine the pharmacokinetics of Primolut Depot in patients with renal impairment.

8.7 Hepatic Impairment

No studies have been conducted to examine the pharmacokinetics of Primolut Depot in patients with hepatic impairment. Primolut Depot is extensively metabolized and hepatic impairment may reduce the elimination of Primolut Depot.

10 OVERDOSAGE

There have been no reports of adverse events associated with overdosage of Primolut Depot in clinical trials. In the case of overdosage, the patient should be treated symptomatically.

11 DESCRIPTION

The active pharmaceutical ingredient in Primolut Depot is Primolut Depot.

The chemical name for Primolut Depot 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. Primolut Depot exists as white to practically white crystals or powder with a melting point of 120°-124°C.

The structural formula is:

Primolut Depot is a clear, yellow, sterile, non-pyrogenic solution for intramuscular injection. Each 1 mL single dose vial contains Primolut Depot USP, 250 mg/mL (25% w/v), in castor oil USP (30.6% v/v) and benzyl benzoate USP (46% v/v). Each 5 mL multidose vial contains Primolut Depot 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).

Chemical Structure for Primolut Depot

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Primolut Depot is a synthetic progestin. The mechanism by which Primolut Depot reduces the risk of recurrent preterm birth is not known.

12.2 Pharmacodynamics

No specific pharmacodynamic studies were conducted with Primolut Depot.

12.3 Pharmacokinetics

Absorption: Female patients with a singleton pregnancy received intramuscular doses of 250 mg Primolut Depot for the reduction of preterm birth starting between 16 weeks 0 days and 20 weeks 6 days. All patients had blood drawn daily for 7 days to evaluate pharmacokinetics.

For all three groups, peak concentration (C_max) and area under the curve (AUC_{(1-7 days)}) of the mono-hydroxylated metabolites were approximately 3-8-fold lower than the respective parameters for the parent drug, Primolut Depot. While di-hydroxylated and tri-hydroxylated metabolites were also detected in human plasma to a lesser extent, no meaningful quantitative results could be derived due to the absence of reference standards for these multiple hydroxylated metabolites. The relative activity and significance of these metabolites are not known.

The elimination half-life of Primolut Depot, as evaluated from 4 patients in the study who reached full-term in their pregnancies, was 16.4 (±3.6) days. The elimination half-life of the mono-hydroxylated metabolites was 19.7 (±6.2) days.

Distribution: Primolut Depot binds extensively to plasma proteins including albumin and corticosteroid binding globulins.

Metabolism: In vitro studies have shown that Primolut Depot can be metabolized by human hepatocytes, both by phase I and phase II reactions. Primolut Depot undergoes extensive reduction, hydroxylation and conjugation. The conjugated metabolites include sulfated, glucuronidated and acetylated products. In vitro data indicate that the metabolism of Primolut Depot is predominantly mediated by CYP3A4 and CYP3A5. The in vitro data indicate that the caproate group is retained during metabolism of Primolut Depot.

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 Primolut Depot has not been evaluated.

Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of Primolut Depot has not been evaluated.

Drug Interactions

Cytochrome P450 (CYP) enzymes: An in vitro inhibition study using human liver microsomes and CYP isoform-selective substrates indicated that Primolut Depot increased the metabolic rate of CYP1A2, CYP2A6, and CYP2B6 by approximately 80%, 150%, and 80%, respectively. However, in another in vitro study using human hepatocytes under conditions where the prototypical inducers or inhibitors caused the anticipated increases or decreases in CYP enzyme activities, Primolut Depot did not induce or inhibit CYP1A2, CYP2A6, or CYP2B6 activity. Overall, the findings indicate that Primolut Depot has minimal potential for CYP1A2, CYP2A6, and CYP2B6 related drug-drug interactions at the clinically relevant concentrations.

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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Primolut Depot has not been adequately evaluated for carcinogenicity.

No reproductive or developmental toxicity or impaired fertility was observed in a multigenerational study in rats. Primolut Depot 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.

14 CLINICAL STUDIES

14.1 Clinical Trial to Evaluate Reduction of Risk of Preterm Birth

In a multicenter, randomized, double-blind, vehicle -controlled clinical trial, the safety and effectiveness of Primolut Depot 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 Primolut Depot (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-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 5.

Compared to controls, treatment with Primolut Depot 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 Primolut Depot. 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-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

The rates of fetal losses and neonatal deaths in each treatment arm are displayed in Table 6. Due to the higher rate of miscarriages and stillbirths in the Primolut Depot arm, there was no overall survival difference demonstrated in this clinical trial.

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 Primolut Depot arm (11.9% vs. 17.2%), the number of adverse outcomes was limited and thedifference between arms was not statistically significant.

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

14.2 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-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

15 REFERENCES

¹Meis 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.

²Northen 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.

16 HOW SUPPLIED/STORAGE AND HANDLING

Primolut Depot (NDC 64011-247-02) is supplied as 1 mL of a sterile solution in a single dose glass vial.

Each 1 mL vial contains Primolut Depot USP, 250 mg/mL (25% w/v), in castor oil USP (30.6% v/v) and benzyl benzoate USP (46% v/v).

Single unit carton: Contains one 1 mL single dose vial of Primolut Depot containing 250 mg of Primolut Depot.

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

Each 5 mL vial contains Primolut Depot 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 Primolut Depot (250 mg/mL) containing 1250 mg of Primolut Depot.

Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° – 30°C (59° – 86°F). Do not refrigerate. Use multidose vials within 5 weeks after first use.

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

17 PATIENT COUNSELING INFORMATION

Counsel patients that Primolut Depot 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 .

Distributed by:

AMAG Pharmaceuticals, Inc.

Waltham, MA 02451

08/2017

Patient Information

Primolut Depot (mah-KEE-na)

(hydroxyprogesterone caproate injection) 250 mg/mL

Read this Patient Information Leaflet before you receive Primolut Depot. 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 Primolut Depot?

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

Primolut Depot is for women who:

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

How well does Primolut Depot work?

Primolut Depot 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 Primolut Depot gave birth preterm (before 37 weeks of pregnancy), compared to about 55 of 100 women who did not receive Primolut Depot. Another study of Primolut Depot is going on to see whether Primolut Depot reduces the number of babies who have serious problems shortly after birth or who die.

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

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

Primolut Depot is not intended for use to stop active preterm labor.

Who should not receive Primolut Depot?

Primolut Depot 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 Primolut Depot?

Before you receive Primolut Depot, tell your healthcare provider if you have:

• An allergy to Primolut Depot, castor oil, or any of the other ingredients in Primolut Depot. See the end of this patient leaflet for a complete list of the ingredients in Primolut Depot.
• 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.

Primolut Depot may affect the way other medicines work, and other medicines may affect how Primolut Depot 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 Primolut Depot?

• Do not give yourself Primolut Depot injections. A healthcare professional will give you the Primolut Depot injection into your hip area (upper outer area of the buttocks) once a week (every 7 days).
• You will start receiving Primolut Depot 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 Primolut Depot injections once weekly until week 37 of your pregnancy or when your baby is delivered, whichever happens first.

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

Primolut Depot supplied in multidose 5 mL vials should be used within 5 weeks after the first use.

It is very important that you do not miss a dose of Primolut Depot 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 Primolut Depot?

Primolut Depot 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 Primolut Depot 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 Primolut Depot. 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 Primolut Depot compared to women who did not receive Primolut Depot, 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-FDA-1088.

How should I store Primolut Depot?

• Store Primolut Depot at 20° to 25°C (68° to 77°F). Excursions permitted to 15° – 30°C (59° – 86°F)
• Do Not Refrigerate
• Store Primolut Depot in the original box to protect it from light
• Store the Primolut Depot box upright
• Primolut Depot 5 mL multidose vials should be used within 5 weeks after the first use
• Keep Primolut Depot out of the reach of children

General information about the safe and effective use of Primolut Depot.

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

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

For more information, go to www.makena.com or call AMAG Pharmaceuticals Customer Service at the toll free number 1-877-411-2510.

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

What are the ingredients in Primolut Depot?

Active ingredient: Primolut Depot

Inactive ingredients: castor oil and benzyl benzoate. 5 mL multidose vials also contain benzyl alcohol (a preservative).

Makena®

Primolut Depot injection

1250 mg/5 mL

(250 mg/mL)

Makena®

Primolut Depot injection

250 mg/mL

1 mL vial

Primolut Depot pharmaceutical active ingredients containing related brand and generic drugs:

• Hydroxyprogesterone Caproate

Primolut Depot available forms, composition, doses:

• Injectable; Injection; Hydroxyprogesterone Caproate 250 mg / ml

Primolut Depot destination | category:

• Human:
• Oestrogens and progesterones and related synthetic drugs

Primolut Depot Anatomical Therapeutic Chemical codes:

• G03DA03 - Hydroxyprogesterone

Primolut Depot pharmaceutical companies:

• Bayer Schering Pharma

References

1. Dailymed."MAKENA (HYDROXYPROGESTERONE CAPROATE) INJECTION [AMAG PHARMACEUTICALS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. Dailymed."HYDROXYPROGESTERONE CAPROATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
3. "HYDROXYPROGESTERONE CAPROATE". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Primolut Depot after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Primolut Depot not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology