5.2Allergic 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.

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 Makena.

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 (e.g., preeclampsia, epilepsy, migraine, asthma, cardiac or renal dysfunction).

5.5 Depression
Monitor women who have a history of clinical depression and discontinue Makena if clinical depression recurs.

5.6 Jaundice
Carefully monitor women who develop jaundice while receiving Makena and consider whether the benefit of use warrants continuation.

5.7 Hypertension
Carefully monitor women who develop hypertension while receiving Makena 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 (5).

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 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 (14.1).]

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).

Table 1 Selected Fetal Complications
1 N = Total number of subjects enrolled prior to 20 weeks 0 days.
2 N = Total number of subjects at risk ≥20 weeks.
Pregnancy Complication Makena Control
 n/N n/N
Miscarriage (<20 weeks)1 5/209 0/107
Stillbirth (≥20 weeks)2 6/305 2/153
Table 2 Selected Maternal Complications
1 Other than delivery admission.
Pregnancy Complication Makena
N=310
% Control
N=153
%
Admission for preterm labor1 16.0 13.8
Preeclampsia or gestational hypertension 8.8 4.6
Gestational diabetes 5.6 4.6
Oligohydramnios 3.6 1.3
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 Mak