Ellaone 30 Mg 1 Coated Tablet

Ellaone (30 Mg 1 Coated Tablet)

ACTION AND MECHANISM
- Emergency contraceptive. Ulipristal acetate is a Ellaone selective modulator (30 Mg 1 Coated Tablet)

ACTION AND MECHANISM

- Emergency contraceptive. Ulipristal acetate is a selective modulator with high affinity for progesterone receptors, where it exerts partial agonist or tissue-dependent effects.

When used in contraceptive doses (30 mg vs. 5 mg used in myomas) it results in an inhibition or delay in ovulation as a result of the suppression of LH release. Even in those situations in which it was administered in the moments prior to ovulation, when LH began to rise, it was able to postpone ovulation in the 5 days following in 78% of women.

Ulipristal acetate has antagonistic effects on glucocorticoid receptors in animals, although they have not been observed in humans. It has no significant affinity for other receptors such as mineralocorticoids, estrogens or androgens.

PHARMACKINETICS

Orally:

- Absorption: administration of single doses (30 mg) resulted in rapid absorption (tmax 1 h, with range 0.5-2 h), with cmax 176 ± 89 ng / ml and AUC 556 ± 260 ng · h / ml.

Food effect: they do not seem to present an important effect that justifies a special recommendation regarding their administration with food. A high-fat breakfast reduced cmax by 45%, increased AUC by 25% and delayed tmax to 0.75-3 h.

- Distribution: high plasma protein binding (> 98%), such as albumin, acidic alpha-1 glycoprotein or HDL. Both ulipristal and the active metabolite are excreted in milk, with a milk / plasma ratio of 0.74 ± 0.32. Neither ulipristal nor mono-N-desmethyl are substrates of P-gp or OATP1B1 / 3 hepatic scavengers.

- Metabolism: it is rapidly metabolized to mono-N-desmethyl-ulipristal, an active metabolite, which is subsequently transformed into the di-N-demethylated, inactive form. The metabolism appears to be mediated by the CYP3A4 isoenzyme, with a minor participation of CYP1A2 and 2A6.

Enzyme inducing / inhibiting capacity: ulipristal and its active metabolite do not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 or 3A4 isoenzymes. Nor do they induce CYP1A2. It acts as a potent inhibitor of P-gp and probably intestinal BCRP.

- Excretion: mainly in feces and to a lesser extent in urine (<10%). Its t1 / 2 is 32.4 ± 6.3 h and the CLt is 76.8 ± 64.0 l / h.

Pharmacokinetics in special situations:

- Other situations: no specific studies have been conducted in girls, elderly women or patients with renal or hepatic impairment.

INDICATIONS

- [EMERGENCY CONTRACEPTION] within 120 hours (5 days) after having had unprotected sex or having produced a contraceptive failure.

POSOLOGY

- Adults: 1 tablet (30 mg) administered as soon as possible, and never after 120 hours (5 days) after having had unprotected sex or having produced the contraceptive failure.

It can be administered at any time during the menstrual cycle.

- Girls and adolescents <18 years:

* Girls at puberty: no dose adjustment is required.

* Prepubertal girls: it is not intended for these patients.

- Elderly women: it is not intended for these patients once menopause is reached.

Measures to be taken in case of vomiting: if the patient vomits within 3 hours after administration, administer a new tablet.

POSOLOGY IN RENAL INSUFFICIENCY

It does not require dosage adjustment, regardless of the degree of renal functionality.

POSOLOGY IN HEPATIC INSUFFICIENCY

- Mild to moderate hepatic impairment (Child-Pugh classes A and B): no specific dosage recommendations could be established due to lack of studies.

- Severe hepatic impairment (Child-Pugh class C): not recommended.

RULES FOR THE CORRECT ADMINISTRATION

Swallow the tablet whole with enough liquid.

Administration with food: can be taken with or without food.

CONTRAINDICATIONS

- Hypersensitivity to ulipristal acetate or any other component of the medicine.

PRECAUTIONS

- [LIVER FAILURE]. Safety and efficacy have not been specifically evaluated, so it has not been possible to verify whether women with mild to moderate insufficiency (Child-Pugh classes A and B) have different safety or efficacy profiles than those with normal liver function. Its use is not advised in severe hepatic impairment (Child-Pugh class C).

- [OVERWEIGHT]. There are very limited data that suggest that women who are overweight or obese may be less effective with ulipristal.

- Limitations in clinical experience. Its use is not recommended in women with severe [ASMA] treated with oral glucocorticoids.

PRECAUTIONS RELATING TO EXCIPIENTS

- This medicine contains lactose. Patients with hereditary or galactose [INTOLERANCE TO LACTOSE], Lapp lactase insufficiency or glucose or galactose malabsorption should not take this medicine.

- This medicine contains lactose. The intake of amounts greater than 5 g daily should be taken into account in patients with [DIABETES] and with intolerance to certain sugars.

PATIENT ADVICE

- Emergency contraceptives are intended exclusively for occasional employment to reduce the risk of pregnancy during sexual intercourse without contraceptive methods or in case of failure of a contraceptive method (eg rupture of condoms, forgetting to take oral contraceptives) . Ulipristal acetate also does not protect against sexually transmitted diseases. Therefore, it should never replace other alternative contraceptive methods.

- Ulipristal acetate delays ovulation, resulting in a contraceptive and non-abortive effect, so it should be taken as soon as possible after sexual intercourse, and never later than 5 days (120 h) later. Its administration once ovulation had occurred would not prevent pregnancy. Keep in mind that no contraceptive method is 100% effective, so it does not prevent pregnancy in all patients.

- After the use of ulipristal acetate, fertility can be recovered quickly in a few days. Use barrier contraceptives during the rest of the menstrual cycle to avoid pregnancy. Ulipristal acetate may reduce the effectiveness of hormonal contraceptives.

- If, despite the use of ulipristal acetate, you suspect that you may be pregnant, consult your doctor. Ulipristal acetate does not exert any abortion effects.

- If you are breastfeeding, you should avoid breastfeeding during the week after administration.

SPECIAL WARNINGS

- Confirm a possible pregnancy in case of delayed menstruation, abnormal menstruation or any other symptoms. Ulipristal can have an effect on the menstrual cycle itself, advancing it up to 7 days (approximately 7% of women) or delaying it for periods of 7 days or more (up to 18% of women).

INTERACTIONS

Ulipristal acts as a potent inhibitor of P-gp and probably intestinal BCRP. However, these effects are unlikely to have clinical consequences in the case of a single administration of ulipristal. Similarly, potent CYP3A4 inhibitors are not expected to result in a significant increase in ulipristal levels after a single dose.

- Progestagenic contraceptives. The ulipristal has a predominantly antagonistic effect of progestagenic receptors, so it could oppose the effects of contraceptives with progestogens, as well as those of the ulipristal. It is recommended to avoid using together with progestogen contraceptives (eg levonorgestrel) alone or in combination, including IUDs with progestogens.

- Esomeprazole. Joint administration reduced ulipristal cmax, increased AUC and delayed tmax. It is unknown if these effects have implications in the clinical response of ulipristal, and if they could reproduce with other PPIs such as omeprazole.

- CYP3A4 inductors. The levels of ulipristal and its effects could decrease due to the increase in its metabolism by drugs such as carbamazepine, efavirenz, phenytoin, phenobarbital, rifampicin or hypericum. Due to the prolonged enzymatic induction, other emergency contraceptive methods are advised in women who have received a potent CYP3A4 inducer in the previous 4 weeks.

PREGNANCY

Safety in animals : no teratogenic effects have been observed in doses that maintained pregnancy in animals. Ulipristal resulted in increased fetal mortality in rat (dose <DMRH), rabbit or mona (3 DMRH).

Safety in humans : adequate and well-controlled studies in humans are not available. Ulipristal acetate is not intended for use in pregnant women, and should not be used during this period. Despite this, it does not exert abortive effects.

If there is suspicion of pregnancy (period delay> 7 days, abnormal menstruation or any other symptoms), a test should be performed to rule it out or confirm it. It must be taken into account that alterations in the menstrual cycle associated with the ulipristal itself have been frequently described. Approximately 7% of women saw menstruation advanced up to 7 days, while 18% delayed 7 days (4% delayed up to 20 days).

In the event that the woman became pregnant, and as with any contraceptive, the possibility of ectopic pregnancy should be assessed. It is advisable to notify these pregnancies to the head laboratory for risk analysis.

Fertility effects : no specific studies have been conducted in humans. The woman is likely to recover fertility quickly after administration.

LACTATION

Animal safety: no data available.

Safety in humans: ulipristal and its active metabolite are lipophilic substances, so they are excreted in milk. After administration of a dose of 30 mg, 13.35 micrograms were recovered with milk in the first 24 hours and 0.31 micrograms after 96-120 hours. The consequences that it could have for the infant are unknown, so it would be advisable to suspend breastfeeding for at least 1 week. To prevent the inhibition of milk production, it would be advisable for the woman to withdraw the milk and discard it.

CHILDREN

Ulipristal acetate can be used in any girl or teenager once menstruation has occurred. No differences in safety or efficacy have been observed between adolescents and adult women.

It is not intended for employment in pre-hierarchical girls, so it is recommended to avoid its use.

ELDERLY

Ulipristal acetate is intended for emergency contraception, so there is no recommendation for use in women after menopause.

EFFECTS ON DRIVING

It is unlikely to have important effects, although dizziness or headache often appear, and sometimes visual disturbances, migraines or drowsiness are rare.

ADVERSE REACTIONS

Adverse reactions are described according to each frequency range, being considered very frequent (> 10%), frequent (1-10%), rare (0.1-1%), rare (0.01-0.1%) , very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

- Digestive: frequent [NAUSEAS], [VOMITOS], [ABDOMINAL PAIN]; uncommon [DIARREA], [DYSPEPSY], [FLATULENCE], [MOUTH DROUGHT].

- Cardiovascular: uncommon [SOFOCOS].

- Neurological / psychological: frequent [CEFALEA], [MAREO], mood alterations; uncommon [SOMNOLENCE], [MIGRAINE], [ANXIETY], [INSOMNIUM], [INCREASE OF THE LIBIDO], [DECREASE OF THE LIBIDO], [HYPERACTIVITY]; rare [TEMBLOR], [SINCOPE], [DYSGEUSIA], [ATTENTION DEFICIT], [DESORIENTATION].

- Respiratory: rare dry throat.

- Genitourinary: frequent [DISMENORREA], [INCREASE IN MATERIAL SENSITIVITY], [PELVIC PAIN]; uncommon [MENORRAGY], [METRORRAGY], [VAGINITIS], [PREMENSTRUAL SYNDROME], [EXCESSIVE VAGINAL SECRETION]; Rare [VAGINAL PRURIUM], [DISPAREUNIA], vulvar or vaginal pain, hypomenorrhea, rupture of ovarian cyst.

- Dermatological: uncommon [ACNE], [PRURITE]; rare [URTICARIA].

- Osteomuscular: frequent [MIALGIA], [BACK PAIN].

- Ophthalmological: uncommon [VISION DELETE] and other visual disorders; rare [CONJUNCTIVE HYPEREMIA], [PHOTOPHOBIA] or abnormal sensation in the eyes.

- Óticas: rare [VERTIGO].

- Metabolic: uncommon [ANOREXIA] or [APPETIZE INCREASE].

- Infectious: uncommon [FLU].

- General: frequent [FATIGUE]; uncommon [ESCALOFRIOS], [FEVER], [MALESTAR GENERAL]; rare [POLYPSYPSY].

ADVERSE REACTIONS CONCERNING EXCIPIENTS

- This medicine contains lactose, which may have milk proteins. It could cause [HYPERSENSITIVITY REACTIONS] in people with a cow's milk protein allergy.

OVERDOSE

Symptoms: very limited experience. Single doses of up to 200 mg (almost 7 DMRH) have been administered, which were well tolerated, with abnormalities of the menstrual cycle usually appearing, although these symptoms already appear with the usual doses.

Measures to take:

- Antidote: there is no specific antidote.

- General measures of elimination: it does not seem necessary to take any action.

- Monitoring: clinical status of the patient.

- Treatment: symptomatic.

with high affinity for progesterone receptors, where it exerts partial agonist or antagonistic effects depending on the tissue.

When used in contraceptive doses (30 mg vs. 5 mg used in myomas) it results in an inhibition or delay in ovulation as a result of the suppression of LH release. Even in those situations in which it was administered in the moments prior to ovulation, when LH began to rise, it was able to postpone ovulation in the 5 days following in 78% of women.

Ulipristal acetate has antagonistic effects on glucocorticoid receptors in animals, although they have not been observed in humans. It has no significant affinity for other receptors such as mineralocorticoids, estrogens or androgens.

PHARMACKINETICS
Orally:

- Absorption: administration of single doses (30 mg) resulted in rapid absorption (tmax 1 h, with range 0.5-2 h), with cmax 176 ± 89 ng / ml and AUC 556 ± 260 ng · h / ml.

Food effect: they do not seem to present an important effect that justifies a special recommendation regarding their administration with food. A high-fat breakfast reduced cmax by 45%, increased AUC by 25% and delayed tmax to 0.75-3 h.

- Distribution: high plasma protein binding (> 98%), such as albumin, acidic alpha-1 glycoprotein or HDL. Both ulipristal and the active metabolite are excreted in milk, with a milk / plasma ratio of 0.74 ± 0.32. Neither ulipristal nor mono-N-desmethyl are substrates of P-gp or OATP1B1 / 3 hepatic scavengers.

- Metabolism: it is rapidly metabolized to mono-N-desmethyl-ulipristal, an active metabolite, which is subsequently transformed into the di-N-demethylated, inactive form. The metabolism appears to be mediated by the CYP3A4 isoenzyme, with a minor participation of CYP1A2 and 2A6.

Enzyme inducing / inhibiting capacity: ulipristal and its active metabolite do not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 or 3A4 isoenzymes. Nor do they induce CYP1A2. It acts as a potent inhibitor of P-gp and probably intestinal BCRP.

- Excretion: mainly in feces and to a lesser extent in urine (<10%). Its t1 / 2 is 32.4 ± 6.3 h and the CLt is 76.8 ± 64.0 l / h.

Pharmacokinetics in special situations:

- Other situations: no specific studies have been conducted in girls, elderly women or patients with renal or hepatic impairment.

INDICATIONS
- [EMERGENCY CONTRACEPTION] within 120 hours (5 days) after having had unprotected sex or having produced a contraceptive failure.

POSOLOGY
- Adults: 1 tablet (30 mg) administered as soon as possible, and never after 120 hours (5 days) after having had unprotected sex or having produced the contraceptive failure.

It can be administered at any time during the menstrual cycle.

- Girls and adolescents <18 years:

* Girls at puberty: no dose adjustment is required.

* Prepubertal girls: it is not intended for these patients.

- Elderly women: it is not intended for these patients once menopause is reached.

Measures to be taken in case of vomiting: if the patient vomits within 3 hours after administration, administer a new tablet.

POSOLOGY IN RENAL INSUFFICIENCY
It does not require dosage adjustment, regardless of the degree of renal functionality.

POSOLOGY IN HEPATIC INSUFFICIENCY
- Mild to moderate hepatic impairment (Child-Pugh classes A and B): no specific dosage recommendations could be established due to lack of studies.

- Severe hepatic impairment (Child-Pugh class C): not recommended.

RULES FOR THE CORRECT ADMINISTRATION
Swallow the tablet whole with enough liquid.

Administration with food: can be taken with or without food.

CONTRAINDICATIONS
- Hypersensitivity to ulipristal acetate or any other component of the medicine.

PRECAUTIONS
- [LIVER FAILURE]. Safety and efficacy have not been specifically evaluated, so it has not been possible to verify whether women with mild to moderate insufficiency (Child-Pugh classes A and B) have different safety or efficacy profiles than those with normal liver function. Its use is not advised in severe hepatic impairment (Child-Pugh class C).

- [OVERWEIGHT]. There are very limited data that suggest that women who are overweight or obese may be less effective with ulipristal.

- Limitations in clinical experience. Its use is not recommended in women with severe [ASMA] treated with oral glucocorticoids.

PRECAUTIONS RELATING TO EXCIPIENTS
- This medicine contains lactose. Patients with hereditary or galactose [INTOLERANCE TO LACTOSE], Lapp lactase insufficiency or glucose or galactose malabsorption should not take this medicine.

- This medicine contains lactose. The intake of amounts greater than 5 g daily should be taken into account in patients with [DIABETES] and with intolerance to certain sugars.

PATIENT ADVICE
- Emergency contraceptives are intended exclusively for occasional employment to reduce the risk of pregnancy during sexual intercourse without contraceptive methods or in case of failure of a contraceptive method (eg rupture of condoms, forgetting to take oral contraceptives) . Ulipristal acetate also does not protect against sexually transmitted diseases. Therefore, it should never replace other alternative contraceptive methods.

- Ulipristal acetate delays ovulation, resulting in a contraceptive and non-abortive effect, so it should be taken as soon as possible after sexual intercourse, and never later than 5 days (120 h) later. Its administration once ovulation had occurred would not prevent pregnancy. Keep in mind that no contraceptive method is 100% effective, so it does not prevent pregnancy in all patients.

- After the use of ulipristal acetate, fertility can be recovered quickly in a few days. Use barrier contraceptives during the rest of the menstrual cycle to avoid pregnancy. Ulipristal acetate may reduce the effectiveness of hormonal contraceptives.

- If, despite the use of ulipristal acetate, you suspect that you may be pregnant, consult your doctor. Ulipristal acetate does not exert any abortion effects.

- If you are breastfeeding, you should avoid breastfeeding during the week after administration.

SPECIAL WARNINGS
- Confirm a possible pregnancy in case of delayed menstruation, abnormal menstruation or any other symptoms. Ulipristal can have an effect on the menstrual cycle itself, advancing it up to 7 days (approximately 7% of women) or delaying it for periods of 7 days or more (up to 18% of women).

INTERACTIONS
Ulipristal acts as a potent inhibitor of P-gp and probably intestinal BCRP. However, these effects are unlikely to have clinical consequences in the case of a single administration of ulipristal. Similarly, potent CYP3A4 inhibitors are not expected to result in a significant increase in ulipristal levels after a single dose.

- Progestagenic contraceptives. The ulipristal has a predominantly antagonistic effect of progestagenic receptors, so it could oppose the effects of contraceptives with progestogens, as well as those of the ulipristal. It is recommended to avoid using together with progestogen contraceptives (eg levonorgestrel) alone or in combination, including IUDs with progestogens.

- Esomeprazole. Joint administration reduced ulipristal cmax, increased AUC and delayed tmax. It is unknown if these effects have implications in the clinical response of ulipristal, and if they could reproduce with other PPIs such as omeprazole.

- CYP3A4 inductors. The levels of ulipristal and its effects could decrease due to the increase in its metabolism by drugs such as carbamazepine, efavirenz, phenytoin, phenobarbital, rifampicin or hypericum. Due to the prolonged enzymatic induction, other emergency contraceptive methods are advised in women who have received a potent CYP3A4 inducer in the previous 4 weeks.

PREGNANCY
Safety in animals: no teratogenic effects have been observed in doses that maintained pregnancy in animals. Ulipristal resulted in increased fetal mortality in rat (dose <DMRH), rabbit or mona (3 DMRH).

Safety in humans: adequate and well-controlled studies in humans are not available. Ulipristal acetate is not intended for use in pregnant women, and should not be used during this period. Despite this, it does not exert abortive effects.

If there is suspicion of pregnancy (period delay> 7 days, abnormal menstruation or any other symptoms), a test should be performed to rule it out or confirm it. It must be taken into account that alterations in the menstrual cycle associated with the ulipristal itself have been frequently described. Approximately 7% of women saw menstruation advanced up to 7 days, while 18% delayed 7 days (4% delayed up to 20 days).

In the event that the woman became pregnant, and as with any contraceptive, the possibility of ectopic pregnancy should be assessed. It is advisable to notify these pregnancies to the head laboratory for risk analysis.

Fertility effects: no specific studies have been conducted in humans. The woman is likely to recover fertility quickly after administration.

LACTATION
Animal safety: no data available.

Safety in humans: ulipristal and its active metabolite are lipophilic substances, so they are excreted in milk. After administration of a dose of 30 mg, 13.35 micrograms were recovered with milk in the first 24 hours and 0.31 micrograms after 96-120 hours. The consequences that it could have for the infant are unknown, so it would be advisable to suspend breastfeeding for at least 1 week. To prevent the inhibition of milk production, it would be advisable for the woman to withdraw the milk and discard it.

CHILDREN
Ulipristal acetate can be used in any girl or teenager once menstruation has occurred. No differences in safety or efficacy have been observed between adolescents and adult women.

It is not intended for employment in pre-hierarchical girls, so it is recommended to avoid its use.

ELDERLY
Ulipristal acetate is intended for emergency contracept