And Levonorgestrel

And Levonorgestrel Uses, Dosage, Side Effects, Food Interaction and all others data.

Folic acid is essential for the production of certain coenzymes in many metabolic systems such as purine and pyrimidine synthesis. It is also essential in the synthesis and maintenance of nucleoprotein in erythropoesis. It also promotes WBC and platelet production in folate-deficiency anaemia.

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as Methotrexate as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF.

In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.

Levonorgestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Levonorgestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.

Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.

And Levonorgestrel
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	And Levonorgestrel
Generic	Ethinyl estradiol + folic acid + levonorgestrel
Weight	0.02mg + 1mg + 0.1mg
Type	Oral kit
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Prophylaxis of megaloblastic anaemia in pregnancy, Supplement for women of child-bearing potential, Folate-deficient megaloblastic anaemia, Prophylaxis of neural tube defect in pregnancy

Levonorgestrel is an emergency contraceptive pill for women. Levonorgestrel should be used within 72 hours of unprotected intercourse. It should not be taken as regular birth control pill. This medicine is also known as morning after pill. Levonorgestrel belongs to a group of medicines called progestogen.

This contraception is used as soon as possible, preferably within 12 hours and no later than 72 hours (3 days) after the unprotected sexual intercourse, particularly. If you have had a sexual intercourse whereas either yourself or your partner did not use a contraceptive method

If you have forgotten to take consecutive 3 regular contraceptive pills
If your partner’s condom has broken, slipped or been improperly removed or if he has forgotten to use it
If you fear that your intrauterine device has been expelled
If your vaginal diaphragm or your contraceptive cap has moved or if have removed it too easily
If you are afraid that the method of coitus interruptus has failed or if you have had sexual intercourse during the period when you are supposed to be fertile while using the rhythm method
In the event of rape

And Levonorgestrel is also used to associated treatment for these conditions: Anaemia folate deficiency, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Latent Iron Deficiency, Neural Tube Defects (NTDs), Vitamin Deficiency, Methotrexate toxicity, Nutritional supplementationEndometrial Hyperplasia, Endometriosis, Hypermenorrhea, Postmenopausal Osteoporosis, Pregnant State, Moderate Menopausal Vasomotor Symptoms, Severe Vasomotor Symptoms Associated With Menopause, Emergency Contraception

How And Levonorgestrel works

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.

Mechanism of action on ovulation

Oral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation.

Mechanism of action in cervical mucus changes

Similar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred. Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation.

Effects on implantation*

The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity.

Mechanism of action in hormone therapy

When combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use.

Dosage

And Levonorgestrel dosage

Supplement for women of child-bearing potential: 0.4 mg daily.

Folate-deficient megaloblastic anaemia: 5 mg daily for 4 mth, up to 15 mg daily in malabsorption states. Continued dosing at 5 mg every 1-7 days may be needed in chronic haemolytic states, depending on the diet and rate of haemolysis.

Prophylaxis of neural tube defect in pregnancy: 4 or 5 mg daily starting before pregnancy and continued through the 1st trimester.

Prophylaxis of megaloblastic anaemia in pregnancy: 0.2-0.5 mg daily.

levonorgestrel 0.75 mg Tablets should be taken at the same time, orally, as soon as possible but within 72 hours after unprotected intercourse. The total dosage for one complete regimen of levonorgestrel consists in a single dose of 1.50 mg levonorgestrel.

Levonorgestrel 1.5 mg Tablets should be taken as soon as possible, preferably within 12 hours, and no later than 72 hours (3 days) after having unprotected sex. Levonorgestrel 1.5 mg tablets can be taken at any time in the menstrual cycle assuming the person is not already pregnant. The tablet should not be chewed but should be swallowed whole with water. If a regular method of contraception, such as the contraceptive pill, is already being used, this can be continued at the regular times. If unprotected intercourse takes place again after the use of Levonorgestrel 1.5 mg tablets (also if this is during the same menstrual cycle), the tablet will not exert its contraceptive effect and there is again the risk of pregnancy.

Levonorgestrel can be taken at any moment during the menstrual cycle. After using an emergency contraception, it is recommended to use a local contraceptive mean (condom, spermicide, cervical cap) until the next menstrual period resume.

The use of Levonorgestrel does not contraindicate the continuation of regular hormonal contraception. If you have used this medicine while you were using an oral contraception (contraceptive pill), you should carry on taking the usual tablets until the end of the treatment. In case no menstrual period occurs in the next pill free period following the use of Levonorgestrel, a pregnancy test should be performed to rule out a pregnancy.

May be taken with or without food.

One tablet should be taken orally with a glass of water.

Side Effects

GI disturbances, hypersensitivity reactions; bronchospasm.

Undesirable effects which have been observed are:

Nausea and vomiting
Dizziness, fatigue, headache
Abdominal pain
A feeling of breast tenderness
Bleeding can occur after taking this medicine

Inform doctor of any unwanted effect which is not mentioned here

Toxicity

IPR-MUS LD₅₀ 85 mg/kg,IVN-GPG LD₅₀ 120 mg/kg, IVN-MUS LD₅₀ 239 mg/kg, IVN-RAT LD₅₀ 500 mg/kg, IVN-RBT LD₅₀ 410 mg/kg

The oral LD50 in rats is greater than 5000 mg/kg.

An overdose of this drug, like other contraceptives, may cause nausea and withdrawal bleeding. Provide symptomatic treatment in the case of a levonorgestrel overdose and contact the local poison control center. There is no specific antidote for a levonorgestrel overdose.

Precaution

Treatment resistance may occur in patients with depressed haematopoiesis, alcoholism, deficiencies of other vitamins. Neonates.

Emergency contraception must be used exceptionally, since

It does not allow to prevent a pregnancy in every instance
The associated hormonal overdosing is not advisable in case of regular intake
It cannot replace a regular contraception

After taking Levonorgestrel, menstrual period usually occurs at the expected date nevertheless, it can occur earlier or later by a few days. After taking this tablet, it is therefore mandatory to check the absence of pregnancy by performing a pregnancy test in case of abnormal bleeding at the date of expected period or in case of menstrual delay of more than 5 days. The use of emergency contraception does not replace the necessary precautions against sexually transmitted diseases and the measures to be taken in case of risk of transmission. If vomiting would occur within 2 hours after taking this medicine it is recommended to take immediately another Levonorgestrel tablet.

Interaction

Antiepileptics, oral contraceptives, anti-TB drugs, alcohol, aminopterin, methotrexate, pyrimethamine, trimethoprim and sulphonamides may result to decrease in serum folate contrations. Decreases serum phenytoin concentrations.

Simultaneous administration of certain anticonvulsant agents (phenobarbiton, phenytoin, primidone, carbamazepin), also other medications such as rafimpicin and griseofulvin can reduce or suppress the effectiveness of this emergency contraception.

Volume of Distribution

Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.

One pharmacokinetic study determined a mean steady-state volume of distribution of 1.5 mg of levonorgestrel to be 162.2 L in those with normal BMI and in the range of 404.7 L to 466.4 L in obese patients with a body mass index of at least 30. Mean volume of distribution in 16 patients receiving 0.75 mg of levonorgestrel in another pharmacokinetic study was 260 L. The Plan B one-step FDA label reports an apparent volume of distribution of 1.8 L/kg.

Elimination Route

Folic acid is absorbed rapidly from the small intestine, primarily from the proximal portion. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the gastrointestinal tract prior to absorption. Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour.

Orally administered levonorgestrel is absorbed in the gastrointestinal tract while levonorgestrel administered through an IUD device is absorbed in the endometrium. Levonorgestrel is absorbed immediately in the interstitial fluids when it is inserted as a subdermal implant. After insertion of the subdermal implant, the Cmax of levonorgestrel is attained within 2-3 days.The Cmax following one dose of 0.75 mg of oral levonorgestrel is reached within the hour after administration, according to one reference. In a pharmacokinetic study of 1.5 mg of levonorgestrel in women with a normal BMI and those considered to be obese (BMI>30), mean Cmax was found to be 16.2 ng/mL and 10.5 ng/mL respectively. Tmax was found to be 2 hours for those with normal BMI and 2.5 hours for patients with increased BMI. The bioavailability of levonorgestrel approaches 100%.

Mean AUC has been shown to be higher in patients with a normal BMI, measuring at 360.1 h × ng/mL versus a range of 197.28 to 208.1 h × ng/mL in an obese group of patients. Obesity may contribute to decreased efficacy of levonorgestrel in contraception.

Half Life

The elimination half-life of a 0.75 mg dose of 1.5 mg of levonorgestrel ranges between 20-60 hours post-administration. A pharmacokinetic study of women with a normal BMI and BMI over revealed an elimination half-life of 29.7 h and 41.0-46.4 hours, respectively. Another pharmacokinetic study revealed a mean elimination half-life of 24.4 hours after a 0.75 mg dose of levonorgestrel was administered to 16 patients.

Clearance

Clearance was found to 4.8 L/h in healthy female volunteers with a normal BMI, and 7.70-8.51 L/h in obese patients after a single 1.5 mg dose. After a 0.75 mg dose of levonorgestrel in 16 patients in another pharmacokinetic study, mean clearance was calculated at 7.06 L/h. Following levonorgestrel implant removal, the serum concentration falls below 100 pg/mL within the first 96 hours and further falls below the sensitivity of detection within the range of 5 days to 2 weeks.

Elimination Route

After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic acid is also excreted in the milk of lactating mothers.

Approximately 45% of an oral levonorgestrel dose and its conjugated or sulfate metabolites are found to be excreted in the urine. Approximately 32% of an orally ingested dose is found excreted in feces, primarily in the form of glucuronide conjugates of levonorgestrel.

Pregnancy & Breastfeeding use

Pregnancy Category A. Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

The medicine is not indicated in case of pre-existing pregnancy and cannot interrupt it in case of failure of this contraceptive mean with persisting pregnancy. Epidemiological studies indicates no adverse effects of progestogen on malformation of a fetus. Lactation is possible. However, since Levonorgestrel is secreted into breast milk it is suggested that you breast feed immediately before taking each tablet and that you skip nursing following each Levonorgestrel tablet administration.