Medroxyprogesterone acetate

Medroxyprogesterone acetate is a contraceptive and antineoplastics agent belonging to the pharmacological class of progestins.

The FDA has approved Medroxyprogesterone for contraceptive use and treating secondary amenorrhea, abnormal uterine bleeding, endometriosis-related pain, endometrial and renal carcinomas, paraphilia in males, and GnRH-dependent precocious puberty.

Medroxyprogesterone acetate absorbs rapidly through the oral route but slowly via IM injection; it enters breast milk, binds primarily to albumin (86-90%), and undergoes hepatic metabolism through CYP450 enzymes and excretes primarily via urine.

The most common side effects of Medroxyprogesterone acetate include headache, abdominal pain, weakness, and dizziness.

Medroxyprogesterone acetate is available as tablets and injectable suspensions (prefilled syringes).

The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.

Medroxyprogesterone acetate is a contraceptive and antineoplastics agent belonging to the pharmacological class of progestins.

The progestogen derivative medroxyprogesterone increases cervical mucus, which hinders sperm entry into the uterus, and suppresses the release of gonadotrophins, which inhibits follicular development and ovulation. It causes the endometrium to change from proliferative to secretory. It may affect endometriosis by suppressing serum estradiol concentrations, which causes endometrial tissue atrophy and lessens the associated pain. Furthermore, high doses of medroxyprogesterone show antitumor action.

Following oral administration, the peak plasma concentration for a single dose of Medroxyprogesterone is 1.01 ng/mL (with 2 x 10-mg doses) and 0.805 ng/mL (with 8 x 2.5-mg doses). In contrast, for multiple doses, it is 0.71 ng/mL (with a 10-mg dose).

The peak plasma time for a single dose is 2.65 ng/mL (with 2 x 10-mg doses) and 2.22 ng/mL (with 8 x 2.5-mg doses). For multiple doses, it is 2.83 ng/mL (with a 10-mg dose).

The AUC for a single dose is 6.95 ng/mL (with 2 x 10-mg doses) and 5.62 ng/mL (with 8 x 2.5-mg doses). For multiple doses, it is 6.01 ng/mL (with a 10-mg dose).

The onset of ovulation following the last injection is typically 10 months, varying between 6 to 12 months.

Medroxyprogesterone acetate is available as tablets and injectable suspension (prefilled syringes).

As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.

Medroxyprogesterone acetate restores hormonal balance, induces regular periods, and regulates menstrual cycles to treat amenorrhea and irregular uterine bleeding effectively. Except for organic diseases like uterine cancer, this medication helps reduce irregular menstruation linked to hormonal imbalances or illnesses like fibroids. It treats endometriosis by inhibiting the formation of abnormal tissue outside the uterus, which eases pelvic pain and unpleasant periods. Medroxyprogesterone acetate considerably improves the quality of life for those dealing with endometriosis by lowering monthly irregularities and related symptoms, such as pelvic discomfort, offering relief and enhancing general well-being.

Oral medroxyprogesterone acetate (MPA) tablets are indicated to treat abnormal uterine bleeding caused by hormonal imbalance rather than organic pathology secondary amenorrhea and to lower the prevalence of endometrial hyperplasia in postmenopausal women. Oral MPA and conjugated estrogen-containing tablets are recommended for treating moderate-to-severe menopausal symptoms, including vasomotor symptoms, vulvar atrophy, and vaginal atrophy, as well as for preventing postmenopausal osteoporosis. Subcutaneous MPA is recommended for managing endometriosis discomfort and preventing pregnancy. In addition to being used at greater dosages for the palliative treatment of renal or endometrial cancer, intramuscular MPA is approved for the prevention of pregnancy.

Orally: Medroxyprogesterone acetate tablets are typically administered orally and taken once daily, with or without food. The medication should be swallowed whole with water.

Parenterally: Healthcare professionals typically administer Medroxyprogesterone acetate suspension intramuscularly. Before issuing the injection, they ensure aseptic techniques, gently shake the vial to mix the suspension appropriately and inject it slowly, following as directed. Upon accurate positioning, depress the plunger and dispose of the syringe following use, adhering to recommended disposal procedures and rotating injection sites to prevent tissue irritation.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Tablets: 2.5mg, 5mg, 10mg

Injectable solutions (prefilled syringe): 150mg/mL, 400mg/mL, 104mg/0.65m

Medroxyprogesterone acetate is available in the form of tablets and injectable suspension.

Metastatic Endometrial Carcinoma: 400 to 1000 mg IM qWeek initially

Metastatic Renal Carcinoma: 400 to 1000 mg IM qWeek initially

Secondary Amenorrhea: 5 or 10 mg PO qDay for 5 to10 days; may start administered at any time

Progestin withdrawal bleeding usually occurs within 3 to 7 days after discontinuing medroxyprogesterone

Abnormal Uterine Bleeding: 5 or 10 mg PO qDay for 5 to 10 days; begin day 16 or 21 of the menstrual cycle

Progestin withdrawal bleeding usually occurs within 3 to 7 days after discontinuing medroxyprogesterone

Endometrial Hyperplasia Reduction: Starting on the first or sixteenth day of the cycle, postmenopausal women receiving daily 0.625 mg conjugated estrogens should take 5 or 10 mg PO qDay for 12 to 14 days in consecutive weeks each month. Start at the lowest dose.

Lowest effective dose has not been determined.

Contraception: 104 mg SC every 12 to14 weeks

Sexually active women who have regular menses: Only administer the first injection within the first five days of a normal menstrual cycle.

Breastfeeding women: Administer first injection during or after the sixth postpartum week

Endometriosis-Associated Pain:104 mg SC every 12 to 14 weeks

Sexually active women who have regular menses: Only administer the first injection within the first five days of a normal menstrual cycle.

Breastfeeding women: In the sixth postpartum week or later, administer the first injection.

Not recommended as a long-term (less than two years) method of birth control or as a treatment for discomfort related to endometriosis unless other treatments are deemed insufficient.

While using Medroxyprogesterone acetate, Caffeine intake should be limited to mitigate potential drug interactions and adverse effects. A balanced diet of whole grains, vegetables, fruits, and low-fat dairy can complement the therapy. Smoking cessation and moderation of alcohol significantly reduce the risk of complications. Heart-healthy omega-3 fatty acid sources aid in managing elevated blood pressure. Utilize low-fat cooking oils like olive, soybean, canola, or coconut oil. Reduce caffeine, alcohol, and spicy food intake to ease hot flushes. Manage stress to alleviate hormonal mood swings. Regular monitoring and consultation with a healthcare provider are recommended for optimal management while on Medroxyprogesterone acetate therapy.

The dietary restriction should be individualized as per patient requirements.

Medroxyprogesterone acetate may be contraindicated in the following conditions:-

Undetected excessive vaginal bleeding.

Known or suspected neoplasia that is dependent on progesterone or estrogen.

PE, DVT that is currently active, or a history of these diseases.

A history of these disorders or current arterial thromboembolic illness (stroke, MI, etc.)

Angioedema or known allergic reaction.

Known illness or damage of the liver.

Pregnancy known or suspected.

The adverse reactions related to Medroxyprogesterone acetate can be categorized as

The clinically relevant drug interactions of Medroxyprogesterone acetate are briefly summarized here.

Drug-Drug Interactions: Before taking Medroxyprogesterone acetate, inform your doctor if using it as it may have an interaction with medicines, including anticonvulsants (e.g. Acetazolamide, Carbamazepine), anti-infectives (e.g. Metronidazole, Clindamycin), and herbal preparation (e.g. Ginkgo Biloba and St. John’s wort plant).

Drug-Food Interactions: Grapefruit juice may interact with Medroxyprogesterone acetate. Hence, refrain from consuming grapefruit juice 24 hours before taking Medroxyprogesterone acetate.

Drug-Disease Interactions: Avoid Medroxyprogesterone acetate if you have abnormal genital bleeding, low level of bone mineral, breast cancer, liver disease, and thromboembolism (blood clot problem).

The common side effects of Medroxyprogesterone acetate include: -

Breast pain

Irregular vaginal bleeding or spotting

Stomach/abdominal cramps

Bloating

Nausea

Vomiting

Hair loss

Headache

Weakness

Dizziness

Nervousness

Pregnancy Category X (FDA): When pregnant, avoid using. The risks outweigh the potential benefits. There are safer alternatives available.

Medroxyprogesterone should not be used when pregnant because it has no purpose in pregnancy.

Early pregnancy birth abnormalities were either not significantly or not at all elevated in risk for women who may have received medroxyprogesterone injections.

The potential for fetal damage from medroxyprogesterone acetate given to a pregnant woman is unknown.

Since medroxyprogesterone acetate is an antifertility medication, high dosages are expected to reduce fertility until therapy is stopped.

Studies have published the detection of medroxyprogesterone acetate in human milk. Administering medroxyprogesterone acetate to a nursing woman should be approached with caution. Although detectable in mothers receiving DMPA-IM, it doesn't adversely impact milk composition, quality, or amount. However, the effects on milk production and lactation initiation/duration are uncertain when given before 6 weeks post-delivery.

The safety and efficacy of Medroxyprogesterone acetate in pediatric patients haven't been adequately established. Its use in this demographic requires careful consideration, monitoring, and adherence to specific guidelines due to potential risks and limited clinical data.

Duration of 12–14 weeks at 104 mg SC

Women who are regularly menstruating and sexually active: Deliver the initial injection within the initial five days of a typical menstrual cycle.

Giving a first injection to nursing mothers should happen during or after the sixth postpartum week.

Due to the effects of prolonged use on bone mineral density (BMD), it is not advised to use for longer than two years (unless alternative birth control options or medical treatments for endometriosis-related discomfort are deemed insufficient).

Renal impairment: Contraindicated

IM

Women who have severe liver illness should not use this medication; stop using it if they experience jaundice or other liver function issues.

PO

Hepatic metabolism removes the majority of medroxyprogesterone (MPA).

MPA disposition was dramatically changed (lower elimination) in patients with severe liver disease.

The mean per cent dose excreted as intact MPA in the 24-hour urine after a dose of 10 mg or 100 mg was 6.4% and 7.3%, respectively, in patients with fatty liver.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Medroxyprogesterone acetate.

Overconsumption of Medroxyprogesterone acetate could lead to severe nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue breast tenderness, dizziness, abdominal pain, and withdrawal bleeding may occur in women.

There is no specific antidote or treatment for excessive Medroxyprogesterone acetate, so treatment typically involves symptomatic and supportive measures. Activated charcoal may limit absorption if the ingestion is recent. Nausea, vomiting, and abdominal discomfort can be managed symptomatically. Hemodialysis is unlikely to be effective in reducing Medroxyprogesterone acetate levels due to its high protein binding and extensive tissue distribution. Close vital sign monitoring is crucial, emphasizing timely medical intervention to mitigate potential risks from Medroxyprogesterone acetate overdose.

Metoprogesterone acetate (MPA) suppresses gonadotropin synthesis, lowers nuclear estrogen receptors and DNA synthesis in endometrial epithelial cells, and causes p53-dependent apoptosis in cancer cell lines. The duration of the effect is prolonged by the half-life of MPA oral tablets, which ranges from 40 to 60 hours. Other formulations may have half-lives that are significantly longer. Patients have a broad therapeutic window with dosages ranging from 5 mg taken orally daily to 1000 mg administered as a weekly depo injection. Long-term MPA use is linked to a decrease in bone density, and patients who started taking the medication in their youth may have had a lower peak bone mass than those who did not receive treatment. This can raise the risk of osteoporosis and fractures in the future.

It rapidly absorbs from the gastrointestinal tract orally but slowly after IM injection, showing increased bioavailability with food (0.6-10%). Its peak plasma concentration occurs in approximately 2-4 hours orally, around three weeks via IM, and about one week subcutaneously.

It enters breast milk and binds mainly to albumin (86-90%).

The liver metabolizes it via CYP450 enzymes through hydroxylation and conjugation.

It's primarily excreted via urine as a glucuronide conjugate, with an elimination half-life of approximately 12-17 hours orally, about 50 days via IM, and roughly 43 days subcutaneously.