ivery 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 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 2.0
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.
Drug Interactions
No drug-drug interaction studies were conducted with Makena.
Drugs Metabolized by CYP1A2, CYP2A6 and CYP2B6
The metabolism of drugs metabolized by CYP1A2 (such as theophylline, tizanidine, clozapine), CYP2A6 (such as acetaminophen, halothane, nicotine) and CYP2B6 (such as efavirenz, bupropion, methadone) may be increased during treatment with Makena [See Clinical Pharmacology (12.3)] .
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 infants 2, 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 num |
