MAKENA

Hazard statements (CLP)

H360DF, H400

2.1 Classification of the substance or mixture

Drugs in the finished state and intended for the final user are not subject to labeling in the US, EU or Canada. Please consult the prescribing/packaging information. The classification and labeling listed below is for bulk drug product. Globally Harmonized Reproductive Toxicity - Category 1A. Aquatic toxicity (acute) - Category 1. System [GHS] SECTION 2 - HAZARDS IDENTIFICATION …continued

Signal word

Danger

Hazard statements

H360DF - May damage fertility or the unborn child. H400 - Very toxic to aquatic life. precautions have been read and understood. P273 - Avoid release to the environment. P281 - Use personal protective equipment as required. P308 + P313 - If exposed or concerned: get medical advice/attention. P391 - Collect spillage. P405 - Store locked up. P501 - Dispose of contents/container to location in accordance with local/regional/national/international regulations.

Precautionary statements

P201 - Obtain special instructions before use. P202 - Do not handle until all safety

2.3 Other hazards

Each 5 mL multidose vial contains 1250 mg hydroxyprogesterone caproate. 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. 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. The most commonly reported adverse effects include injection site reactions (pain, swelling, itchiness) gastrointestinal (GI) discomfort, headache, dizziness, depression, chest discomfort, difficulty breathing, and urinary tract infections, changes to the cervix, and premature rupture of membranes. An increased incidence of fetal and maternal complications was observed, including miscarriage and stillbirth, preterm labor, gestational hypertension, and gestational diabetes. There are no adequate and well- controlled studies of Makena use in women during the first trimester of pregnancy. Data from a placebo-controlled clinical trial did not demonstrate any teratogenic risks to infants from in utero exposure to Makena during the second or third trimesters. Though not currently indicated for this purpose, hydroxyprogesterone caproate has been used in non-pregnant women to treat menstrual disorders. Note This product is classified as hazardous according to Regulation EC No 1272/2008 (EU CLP) and Hazard Communication Standard No. 1910.1200 (US OSHA).