Zacafemyl
Zacafemyl Uses, Dosage, Side Effects, Food Interaction and all others data.
Zacafemyl is a synthetic steroid which blocks the effects of progesterone by competitively binding to the intracellular progesterone receptor. It sensitises the myometrium to the contraction-inducing action of prostaglandin. At higher doses, it blocks the effect of cortisol at the glucocorticoid receptor while increasing circulating cortisol concentrations.
Zacafemyl is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Zacafemyl also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
Trade Name | Zacafemyl |
Availability | Prescription only |
Generic | Mifepristone |
Mifepristone Other Names | Mifepriston, Mifepristona, Mifépristone, Mifepristone, Mifepristonum |
Related Drugs | dexamethasone, Decadron, misoprostol, cyproheptadine, oxytocin, Cytotec, Pitocin, Cervidil, Hemabate |
Type | |
Formula | C29H35NO2 |
Weight | Average: 429.5937 Monoisotopic: 429.266779369 |
Protein binding | 98% (bound to plasma proteins, albumin and a 1-acid glycoprotein) |
Groups | Approved, Investigational |
Therapeutic Class | Drugs acting on the Uterus |
Manufacturer | |
Available Country | Mexico |
Last Updated: | September 19, 2023 at 7:00 am |
![Zacafemyl Zacafemyl](https://www.medicinesfaq.com/media/png/zacafemyl.png)
Uses
Zacafemyl is used for:
- As a medical alternative to surgical termination of intra-uterine pregnancy
- Softening and dilatation of the cervix uteri prior to surgical pregnancy termination
- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons
- Labour induction for the expulsion of a dead fetus (fetal death in utero).
Zacafemyl is also used to associated treatment for these conditions: Hyperglycemia, Pregnancy Termination
How Zacafemyl works
The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.
In the treatment of Cushing's syndrome, Zacafemyl blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.
Dosage
Zacafemyl dosage
As a medical alternative to surgical termination of intra-uterine pregnancy in early pregnancy: 600 mg Zacafemyl in a single oral dose followed 36-48 hrs later, by the administration of a prostaglandin analogue Misoprostol 400 mcg orally (up to 49 days) or Gemeprost 1 mg vaginally (up to 63 days).
Softening and dilatation of the cervix uteri prior to surgical pregnancy termination: 200 mg Zacafemyl, followed 36-48 hrs later (but not beyond) by a surgical termination of pregnancy.
Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (to reduce the doses of prostaglandin): 600 mg of Zacafemyl taken in a single oral dose, 36-48 hrs prior to scheduled prostaglandin administration which will be repeated as often as indicated.
Labour induction for expulsion of a dead fetus (fetal death in utero): 600 mg of Zacafemyl in a single oral daily dose for 2 consecutive days. Zacafemyl alone leads to expulsion in about 60%. Labour should be induced by the usual methods if it has not started within 72 hrs following the first administration of Zacafemyl.
There are no precautions for timing in relation to food.
Side Effects
It is very common for women to experience uterine contractions or cramping (10-45%) in the hours following prostaglandin intake. Bleeding increases with gestational age. Heavy bleeding occurs in about 5% of cases and from 0-1.4% may require haemostatic curettage. Uterine rupture, hypotension, skin rashes, urticaria, hot flashes and dizziness have been uncommonly reported.
Toxicity
Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.
Precaution
Zacafemyl is available only in single dose packaging. Administration must be under the supervision of a qualified physician. There are no data on the safety and efficacy of Zacafemyl in women with chronic medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal disease; insulin-dependent diabetes mellitus; severe anemia or heavy smoking. Women who are more than 35 years of age and who also smoke 10 or more cigarettes per day should be treated with caution because such patients were generally excluded from clinical trials of Zacafemyl. Although there is no clinical evidence, the effectiveness of Zacafemyl may be lower if Misoprostol is administered more than two days after Zacafemyl administration.
Interaction
ketoconazole, itraconazole, erythromycin and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampicin, dexamethasone, St John's Wort and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine) may induce mifepristone metabolism (lowering serum levels of Zacafemyl). Based on invitro inhibition information, co-administration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates.
Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of Zacafemyl or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.
Food Interaction
- Avoid grapefruit products. Grapefruit inhibits the metabolism of mifepristone through the CYP3A4 pathway causing increased serum levels of mifepristone.
- Take with food. Taking mifepristone with meals has been shown to increase serum levels of mifepristone.
[Moderate] ADJUST DOSING INTERVAL: Food may significantly increase the plasma concentrations of mifepristone.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mifepristone.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, it should be taken with food to achieve consistent plasma drug levels.
Patients should be advised to avoid consuming grapefruit or grapefruit juice during treatment with mifepristone, as it may cause increased adverse effects such as headache, dizziness, fatigue, nausea, vomiting, cramping, diarrhea, hypokalemia, adrenal insufficiency, vaginal bleeding, arthralgia, peripheral edema, and hypertension.
Because mifepristone is eliminated slowly from the body, the interaction with grapefruit juice may be observed for a prolonged period.
Zacafemyl Drug Interaction
Major: heparin, methylergonovine, promethazine, oxytocinModerate: losartan, testosterone, tamsulosinUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, multivitamin, dextran, low molecular weight, cabergoline, aspirin, acetaminophen / aspirin / caffeine, acetaminophen, omeprazole, levothyroxine, ascorbic acid, cholecalciferol, cetirizine
Zacafemyl Disease Interaction
Major: organ transplant, vaginal bleedingModerate: cardiovascular disease, hepatic impairment, long QT, renal impairment
Elimination Route
The absolute bioavailability of a 20 mg oral dose is 69%
Half Life
18 hours
Elimination Route
Fecal: 83%; Renal: 9%.
Pregnancy & Breastfeeding use
Pregnancy: Zacafemyl is indicated for use in the termination of pregnancy (through 49 days’ pregnancy) and has no other approved indication for use during pregnancy.
Lactation: It is not known whether Zacafemyl is excreted in human milk. Many hormones with a similar chemical structure, however, are excreted in breast milk. Since the effects of Zacafemyl on infants are unknown, breast-feeding women should consult with their health care provider to decide if they should discard their breast milk for a few days following administration of the medications.
Contraindication
Zacafemyl must not be administered if there is doubt as to the existence or age of the pregnancy or if an extra-uterine pregnancy is suspected. An ultrasound scan and/or measurement of Beta-hCG must be performed before administration. For first trimester abortions, Zacafemyl is contraindicated if the pregnancy is beyond 49 days of amenorrhoea when used with Misoprostol, or beyond 63 days of amenorrhoea when used with Gemeprost. Zacafemyl should never be prescribed in patients with chronic adrenal failure, known allergy to Zacafemyl or to any component of the product, severe asthma uncontrolled by corticosteroid therapy, porphyrias and renal failure, liver failure or malnutrition, or during breast feeding. Zacafemyl is a lipophilic compound and may theoretically be excreted in the mother\'s breast milk, however no data is available.
Special Warning
Use in children: Safety and effectiveness in pediatric patients have not been established.
Acute Overdose
Single doses of Zacafemyl up to 2 gm caused no unwanted reaction. In the event of massive ingestion, signs of adrenal failure might occur. Acute intoxication may require admission to hospital and if relevant treatment with dexamethasone.
Storage Condition
Store at 25° C.
Innovators Monograph
You find simplified version here Zacafemyl
Zacafemyl contains Mifepristone see full prescribing information from innovator Zacafemyl Monograph, Zacafemyl MSDS, Zacafemyl FDA label