Short answer: The progesterone injection label lists side effects without percentages: breakthrough bleeding and spotting, changes in menstrual flow, swelling, weight change, breast tenderness, pain or redness where it is injected, skin reactions, acne, depression, fever, sleep changes and nausea. Its warnings cover blood clots, sudden vision changes and eosinophilic pneumonia linked to the sesame oil form. It has no boxed warning.
What Progesterone Injection is approved for: Progesterone injection is approved for amenorrhea (periods that have stopped) and abnormal uterine bleeding caused by hormonal imbalance, when there is no physical cause such as fibroids or uterine cancer (Indications and Usage). The label does not list any other use.
Source
Progesterone Injection, USP, in sesame oil, for intramuscular use, prescribing information and Patient Information. Hikma Pharmaceuticals USA. DailyMed, version published July 10, 2024. DailyMed setid 83cfc12e-75d1-4284-bcc3-beadcbd27171
No. The current Progesterone Injection label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Progesterone Injection.
| Area | Reactions the label lists |
|---|---|
| Bleeding and periods | Breakthrough bleeding; spotting; change in menstrual flow; amenorrhea; changes in cervical erosion and cervical secretions |
| Injection site | Pain, irritation and/or redness at the injection area |
| Body and weight | Edema (swelling); change in weight (increase or decrease); pyrexia (fever) |
| Breast | Breast tenderness and galactorrhea (nipple discharge) |
| Skin and hair | Urticaria, pruritus, edema and generalized rash; acne, alopecia and hirsutism; allergic rash with and without itching |
| Allergy | Anaphylactoid reactions, including eosinophilic pneumonia |
| Liver | Cholestatic jaundice |
| Mood and sleep | Mental depression; insomnia; somnolence |
| Stomach | Nausea |
The label gives no rates and no placebo comparison. Grouping into rows is ours; the reactions are the label's.
The label says a statistically significant link has been shown between estrogen-progestin combination drugs and pulmonary embolism and cerebral thrombosis and embolism, so people on progestin therapy are carefully observed. There is also evidence suggesting a link with eye-nerve problems such as retinal thrombosis and optic neuritis.
With estrogen-progestin combination drugs the label also lists raised blood pressure in susceptible people, premenstrual syndrome, libido and appetite changes, headache, nervousness, fatigue, backache, hair loss, skin eruptions, itching and dizziness.
After a 10 mg intramuscular dose, blood levels peaked at about 8 hours (geometric mean 7 ng/mL) and stayed above baseline for about 24 hours. Doses of 10, 25 and 50 mg gave peak levels of 7, 28 and 50 ng/mL.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not use it. Progesterone injection is not used with a current or past blood clot disorder or stroke, liver disease, known or suspected breast or genital cancer, undiagnosed vaginal bleeding, a missed abortion (pregnancy tissue left in the uterus), or allergy to progesterone injection or sesame oil or seeds.
Blood clots. Prescribers watch for the earliest signs of clotting problems, including vein clots, stroke, pulmonary embolism and retinal clots, and the drug is stopped right away if any is suspected.
Sudden vision changes. The drug is stopped pending an eye exam if there is sudden partial or complete vision loss, bulging eyes, double vision or migraine. It is withdrawn if the exam shows optic disc swelling or retinal blood vessel damage.
Eosinophilic pneumonia. Acute eosinophilic pneumonia has been reported with progesterone in sesame oil, with fever, shortness of breath with low oxygen, and lung changes on imaging, generally 2 to 4 weeks after starting. People improved after it was stopped and a different progesterone form and/or steroids were started. It is stopped right away if these signs appear.
Fluid retention. Progestins can cause fluid retention, so conditions it may affect, such as epilepsy, migraine, asthma, and heart or kidney problems, need careful observation.
Depression. People with a history of depression are watched closely, and the drug is stopped if depression comes back to a serious degree.
Blood sugar and fats. Progestins may affect carbohydrate and lipid metabolism. Lower glucose tolerance has been seen in a small share of people on estrogen-progestin treatment, so people with diabetes are carefully observed.
Kidney problems. Safety in kidney insufficiency has not been established, and progesterone is given with caution and careful monitoring.
From the Patient Information that comes with Progesterone Injection:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.