Norgestrelum

Uses

Norgestrelum in combination with ethinyl estradiol is used for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Norgestrelum is also used to associated treatment for these conditions: Abnormal Uterine Bleeding, Endometriosis, Hypermenorrhea, Menstrual Distress (Dysmenorrhea), Polycystic Ovarian Syndrome, Emergency Contraception, Oral Contraceptives

How Norgestrelum works

Norgestrelum (and more specifically the active stereoisomer levonorgestrel) binds to the progesterone and estrogen receptors within the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. Loss of the LH surge inhibits ovulation and thereby prevents pregnancy.

Dosage

Norgestrelum dosage

0.075 mg at same time each day

Side Effects

Edema, Weakness, Anorexia, Amenorrhea, Breakthrough bleeding, Change in menstrual flow, Spotting

Precaution

• Documented hypersensitivity
• Active or history of breast cancer
• Thrombophlebitis, DVT/PE, thrombogenic valvular disease
• Estrogen-dependent neoplasia
• Liver disease, liver tumors
• Undiagnosed abnormal vaginal bleeding, uncontrolled hypertension, diabetes mellitus with vascular involvement, jaundice with prior oral contraceptive use, pregnancy, smoking >15 cigarettes/d) and >35 yo, history of migraine w/ aura
• Serum levels near baseline 24 hr after ingestion, so rigid adherence to dosing schedule is essential for efficacy
• DM, asthma, cardiac dysfunction, irregular menstrual bleeding patterns, bone mineral density changes, depression, epilepsy, migraine, renal dysfunction
• Risk of ectopic pregnancy is 0.5%

Food Interaction

• Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of norgestrel.
• Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of norgestrel.
• Take at the same time every day.

[Moderate] MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact with these drugs.

Norgestrelum Alcohol interaction

[Minor] The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory.

The mechanism may be due to enzyme inhibition.

Consider counseling women about this interaction which is unpredictable.

Norgestrelum Cholesterol interaction

[Moderate] Some progestogenic agents may elevate plasma LDL levels and

Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

Norgestrelum Hypertension interaction

[Moderate] Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods.

Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid.

In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and

Norgestrelum Drug Interaction

Unknown: aripiprazole, charcoal, amphetamine / dextroamphetamine, chlorpheniramine, lorazepam, amoxicillin / clavulanate, ethinyl estradiol / levonorgestrel, citalopram, multivitamin with minerals, ciprofloxacin, sulfamethoxazole / trimethoprim, ubiquinone, sulfamethoxazole / trimethoprim, cholecalciferol, prednisone, lvp solution, venlafaxine, esterified estrogens, docusate / ferrous fumarate, cholecalciferol

Norgestrelum Disease Interaction

Major: hepatic neoplasms, breast malignancy, liver disease, thromboembolismModerate: depression, fluid retention, glucose intolerance, retinal thrombosis, thyroid function tests, hyperlipidemiaMinor: weight gain

Pregnancy & Breastfeeding use

Pregnancy Category: X

Lactation: unsafe

Contraindication

• Documented hypersensitivity
• Active or history of breast cancer
• Arterial thromboembolic disease (stroke, MI), thrombophlebitis, DVT/PE, thrombogenic valvular disease
• Estrogen-dependent neoplasia
• Liver disease, liver tumors
• Undiagnosed abnormal vaginal bleeding
• Uncontrolled hypertension
• Diabetes mellitus with vascular involvement
• Jaundice with prior oral contraceptive use, pregnancy, smoking >15 cigarettes/d) and >35 yo, history of migraine with aura
• Pregnancy or use as a diagnostic test for pregnancy

Storage Condition

Should be stored in cool and dry place

Innovators Monograph

You find simplified version here Norgestrelum