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
|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
|Admission for preterm labor1||16||13.8|
|Preeclampsia or gestational hypertension||8.8||4.6|
|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
|Injection site pain||34.8||32.7|
|Injection site swelling||17.1||7.8|
|Injection site pruritus||5.8||3.3|
|Injection site nodule||4.5||2|
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.
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