DEPO-PROGESTIN 150MG/ML INJECTION SUSPENSION

Indications

• Metabolic acidosis
• Energy supplementation in parenteral nutrition
• Support in patients with impaired glucose metabolism

Dosage

Children: Refer to specific clinical guidelines based on the condition being treated and individual patient factors.

Adults: Refer to specific clinical guidelines based on the condition being treated and individual patient factors.

Mechanism of action

Acetate is metabolized primarily in the liver to acetyl-CoA, which enters the citric acid cycle (Krebs cycle) and is utilized for energy production. It can serve as a substrate for gluconeogenesis and fatty acid synthesis, thereby contributing to overall energy homeostasis.

Pharmacodynamics

Acetate's primary action is to provide an alternative energy source for the body, particularly during states of metabolic stress or when glucose availability is low. It helps regulate energy metabolism and can influence lipid metabolism and gluconeogenesis.

Pharmacokinetics

Acetate is absorbed rapidly when administered intravenously or orally. It is distributed widely throughout the body, particularly in tissues with high metabolic activity. The liver metabolizes acetate primarily to acetyl-CoA, and its elimination half-life is relatively short, often requiring continuous administration for sustained effects.

Pregnancy

The safety of acetate during pregnancy has not been fully established. Use should be considered only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether acetate is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Contraception
• Endometrial hyperplasia
• Dysfunctional uterine bleeding
• Endometriosis
• Hormone replacement therapy

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Medroxyprogesterone shares the pharmacologic actions of progestins. It transforms a proliferative endometrium into a secretory one in the presence of adequate endogenous estrogen. It inhibits the secretion of pituitary gonadotropins, preventing follicular maturation and ovulation, and causes endometrial thinning, contributing to its contraceptive effects. It may act at the hypothalamus, maintaining low normal levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during contraceptive use.

Pharmacodynamics

Medroxyprogesterone exhibits slight androgenic activity in animals and has shown some anabolic effects. However, it lacks significant estrogenic activity in humans. The drug has pronounced adrenocorticoid activity in animal studies, but this effect has not been clinically observed in humans. The inhibition of LH and FSH secretion leads to the prevention of ovulation and changes in the endometrium which are critical for its therapeutic uses.

Pharmacokinetics

Medroxyprogesterone is administered via intramuscular or subcutaneous injections, with a typical dosage regimen of 150 mg every three months for contraceptive purposes. Following administration, it is metabolized in the liver and has varying half-life profiles depending on the route of administration. The pharmacokinetics of oral doses (5-10 mg daily) differ significantly, as these doses do not produce the same contraceptive effects due to less effective suppression of gonadotropins.

Interactions

• sugammadex+medroxyprogesterone: Unknown (decreases exposure)

Pregnancy

Medroxyprogesterone is classified as pregnancy category X. It is contraindicated in pregnancy due to the potential for harm to the fetus.

Breast-feeding

Medroxyprogesterone is excreted in breast milk. Caution should be exercised when administering to nursing women, considering the potential risks and benefits.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Mechanism of action

Medroxyprogesterone shares the pharmacologic actions of the progestins. In women with adequate endogenous estrogen, medroxyprogesterone transforms a proliferative endometrium into a secretory one. Medroxyprogesterone has been shown to have slight androgenic activity in animals. Anabolic effects have also been reported, but the drug apparently lacks appreciable estrogenic activity in humans. In animals, the drug exhibits pronounced adrenocorticoid activity, but a clinically important effect has not been observed in humans. Medroxyprogesterone inhibits the secretion of pituitary gonadotropins following usual IM or subcutaneous dosages (eg, 150 or 104 mg every 3 months), thus preventing follicular maturation and ovulation and resulting in endometrial thinning; these effects result in contraceptive activity. Available evidence indicates that these effects do not occur following oral administration of usual dosages (ie, 5-10 mg daily as single daily doses) of the drug. High doses of medroxyprogesterone inhibit pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and will prevent cyclic gonadotropin surges that occur during the normal menstrual cycle. It has been suggested that the drug acts at the hypothalamus since it does not suppress the release of LH and FSH following administration of gonadotropin-releasing hormone and since basal concentrations of LH and FSH remain within the low normal range when the drug is used as a contraceptive. Although the mechanism of action has not been determined, medroxyprogesterone has antineoplastic activity against some cancers (eg, endometrial carcinoma, renal carcinoma). Progestins elicit, to varying degrees, all the pharmacologic responses usually produced by progesterone: induction of secretory changes in the endometrium, increase in basal body temperature (thermogenic action), production of histologic changes in vaginal epithelium, relaxation of uterine smooth muscle, stimulation of mammary alveolar tissue growth, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. /Progestins/ Following binding to cytoplasmic receptor protein, steroid is transported to nucleus, and complex is bound there in reactions analogous to those described... for estrogens. However, there is no apparent need for receptor alteration, as with estrogen receptor. /Progesterone/ Although medroxyprogesterone acetate (MPA) is used as an injectable contraceptive, in hormone replacement therapy (HRT) and in treatment of certain cancers, the steroid receptors and their target genes involved in the actions of MPA are not well understood. /Investigators/ show that MPA, like dexamethasone (dex), significantly represses tumour necrosis factor (TNF)-stimulated interleukin-6 (IL-6) protein production in mouse fibroblast (L929sA) cells. In addition, MPA repressed IL-6 and IL-8 promoter-reporter constructs at the transcriptional level, via interference with nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1). Furthermore, like dex, MPA does not affect NFkappaB DNA-binding activity. /The authors/ also observed significant transactivation by MPA of a glucocorticoid response element (GRE)-driven promoter-reporter construct in both L929sA and COS-1 cells. The MPA-induced nuclear translocation of the glucocorticoid receptor (GR), as well as the antagonistic effects of RU486, strongly suggest that the actions of MPA in these cells are mediated at least in part via the GR. /Investigators/ assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacki