Nerich

Nerich 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.

Inositol is a collection of nine different stereoisomers but the name is usually used to describe only the most common type of inositol, myo-inositol. Myo-inositol is the cis-1,2,3,5-trans-4,6-cyclohexanehexol and it is prepared from an aqueous extract of corn kernels by precipitation and hydrolysis of crude phytate. These molecules have structural similarities to glucose and are involved in cellular signaling. It is considered a pseudovitamin as it is a molecule that does not qualify to be an essential vitamin because even though its presence is vital in the body, a deficiency in this molecule does not translate into disease conditions. Inositol can be found as an ingredient of OTC products by Health Canada but all current product whose main ingredient is inositol are discontinued. By the FDA, inositol is considered in the list of specific substances affirmed as generally recognized as safe (GRAS).

Inositol can stimulate glucose uptake in skeletal muscle cells which allows the decrease in blood sugar levels. This effect is later seen as a reduction in urine glucose concentration and indicates a decrease in high blood sugar levels.

In PCOS, the administration of inositol has produced the remission of symptoms as well as a reduction in male hormone secretion, a regulation of the cholesterol level, and a more efficient fat breakdown which allow to a significant reduction on body mass and appetite.

Melatonin and melatonin agonists inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the melatonin receptor antagonist luzindole, which suggests that melatonin activates a presynaptic melatonin receptor.

Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag.MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions

Nerich
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	Nerich
Generic	Folic Acid + Inositol + Melatonin
Type	Tablet
Therapeutic Class
Manufacturer	Richfield India Pharma Pvt Ltd
Available Country	India
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

Inositol is an ingredient found in a variety of nutritional products.

Inositol may be used in food without any limitation. As a drug, inositol is used as a nutrient supplement in special dietary foods and infant formula. As it presents a relevant role in ensuring oocyte fertility, inositol has been studied for its use in the management of polycystic ovaries. Inositol is also being researched for the treatment of diabetes, prevention of metabolic syndrome, aid agent for weight loss, treatment of depression, psychiatric disorder and anxiety disorder and for prevention of cancer.

Melatonin is used for numerous conditions but is showing the most promise in short-term regulation of sleep patterns, including jet lag.

Insomnia: Melatonin helps to induce sleep in people with-

Disrupted circadian rhythms (such as those suffering from jet lag or poor vision or those who work the night shift)
Low melatonin levels (such as some elderly and individuals with schizophrenia)
Children with learning disabilities who suffer from insomnia.

Osteoporosis: Melatonin stimulates cells called osteoblasts that promote bone growth.

In Menopause:

Melatonin helps peri- or postmenopausal women to regulate sleep patterns.

Eating disorders: Melatonin levels may play a role in the symptoms of anorexia.

Sarcoidosis:

Sarcoidosis is an inflammatory disease that affects multiple organs in the body, but mostly the lungs and lymph glands.

Attention Deficit Hyperactivity Disorder (ADHD): It may be effective in managing sleep disturbances in children with this condition

Nerich 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 supplementationInsomnia

How Nerich 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.

The mechanism of action of inositol in brain disorders is not fully understood but it is thought that it may be involved in neurotransmitter synthesis and it is a precursor to the phosphatidylinositol cycle. The change that occurs in the cycle simulates when the postsynaptic receptor is activated but without activating the receptor. This activity provokes a fake activation which regulated the activity of monoamines and other neurotransmitters.

Reports have shown that insulin resistance plays a key role in the clinical development of PCOS. The presence of hyperinsulinemia can induce an excess in androgen production by stimulating ovaries to produce androgens and by reducing the sex hormone binding globulin serum levels. One of the mechanisms of insulin deficiency is thought to be related to a deficiency in inositol in the inositolphosphoglycans. The administration of inositol allows it to act as a direct messenger of the insulin signaling and improves glucose tissue uptake. This mechanism is extrapolated to its functions in diabetes treatment, metabolic syndrome, and weight loss.

In cancer, the mechanism of action of inositol is not fully understood. It is hypothesized that the administration of inositol increases the level of lower-phosphate inositol phosphates why can affect cycle regulation, growth, and differentiation of malignant cells. On the other hand, the formation of inositol hexaphosphate after administration of inositol presents antioxidant characteristics by the chelation of ferric ions and suppression of hydroxyl radicals.

Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.

Dosage

Nerich 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.

Adult-

Insomnia: 3-6 mg one hour before bedtime

Jet lag: 0.50 to 5 mg one hour prior to bedtime at final destination or, 1 to 5 mg 1 hour before bedtime for 2 days prior to departure and for 2 to 3 days upon arrival at final destination.

Eastbound travel: Take a preflight early evening treatment followed by treatment at bedtime for 4 days after arrival.
Westbound travel: Take for 4 days at bedtime when in the new time zone.

Sarcoidosis:

20 mg per day for 4 to 12 months.

Depression: 0.125 mg twice in the late afternoon, each dose 4 hours apart.

Difficulty falling asleep: 5 mg 3 to 4 hours before an imposed sleep period over a 4-weeks period.

Children-

6 months to 14 years of age with sleep disorders: 0.30 mg/day

May be taken with or without food.

Side Effects

GI disturbances, hypersensitivity reactions; bronchospasm.

Increased seizure activity; drowsiness, headache. Disruption of normal circadian rhythm. May worsen symptoms for individuals with depression.

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

Consumption of high doses of inositol is reported to only cause some gastrointestinal effects.

Generally well-tolerated when taken orally. The most common side effects, day-time drowsiness, headache and dizziness, appear to occur at the same frequency as with placebo. Other reported side effects include transient depressive symptoms, mild tremor, mild anxiety, abdominal cramps, irritability, reduced alertness, confusion, nausea, vomiting, and hypotension. Safety in Adults: Evidence indicates that it is likely safe to use in oral and parenteral forms for up to two months when used appropriately. Some evidence indicates that it can be safely used orally for up to 9 months in some patients. It is also likely safe to use topically when used appropriately. Safety in Children: Melatonin appeared to be used safely in small numbers of children enrolled in short-term clinical trials. However, concerns regarding safety in children have arisen based on their developmental state. Compared to adults over 20 years of age, people under 20 produce high levels of melatonin. Melatonin levels are inversely related to gonadal development and it is thought that exogenous administration of melatonin may adversely affect gonadal development. Safety during Pregnancy: High doses of melatonin administered orally or parenterally may inhibit ovulation. Not advised for use in individuals who are pregnant or trying to become pregnant. Safety during Lactation: Not recommended as safety has not be established.

Oral, rat: LD₅₀ ≥3200 mg/kg

Precaution

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

Caffeine and fluvoxamine may increase the effects of melatonin, while melatonin may decrease the antihypertensive effect of nifedipine.

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.

Antidepressant Medications: Melatonin reduces the antidepressant effects of desipramine and fluoxetine. In addition, fluoxetine leads to measurable depletion of melatonin in people.

Antipsychotic Medications: People with schizophrenia and tardive dyskinesia taking antipsychotic medications with melatonin has significantly reduced mouth movements compared to those who did not take the supplements.

Benzodiazepines: The combination of melatonin and triazolam improves sleep quality. In addition, there have been a few reports suggesting that melatonin supplements may help individuals stop using long-term benzodiazepine therapy.

Blood Pressure Medications: Melatonin may reduce the effectiveness of blood pressure medications like methoxamine and clonidine. In addition, calcium channel blockers (such as nifedipine, verapamil, diltiazem, amlodipine, nimodipine, felodipine, nisoldipine, and bepridil) may decrease melatonin levels. Use of beta-blockers (propranolol, acebutolol, atenolol, labetolol, metoprolol, pindolol, nadolol, sotalol, and timolol) may reduce melatonin production in the body.

Blood-Thinning Medications, Anticoagulants: Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin.

Interleukin 2: In one study of 80 cancer patients, use of melatonin in conjunction with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs such as ibuprofen may reduce the levels of melatonin in the blood.

Steroids and Immunosuppressant Medications: People should not take melatonin with corticosteroids or other medications used to suppress the immune system because the supplement may cause them to be ineffective.

Tamoxifen: Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit certain patients with breast and other cancers.

Other Substances: Caffeine, tobacco, and alcohol can all diminish levels of melatonin in the body while cocaine and amphetamines may increase melatonin production.

Volume of Distribution

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

The pharmacokinetic profile of inositol was studied in preterm infants and the estimated volume of distribution was reported to be 0.5115 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.

Inositol is absorbed from the small intestine. In patients with inositol deficiency, the maximal plasma concentration after oral administration of inositol is registered to be of 4 hours. Inositol is taken up by the tissues via sodium-dependent inositol co-transporter which also mediates glucose uptake. Oral ingestion of inositol is registered to generate a maximal plasma concentration of 36-45 mcg.

The absorption and bioavailability of melatonin varies widely.

Half Life

The pharmacokinetic profile of inositol was studied in preterm infants and the estimated elimination half-life was reported to be of 5.22 hours.

35 to 50 minutes

Clearance

The pharmacokinetic profile of inositol was studied in preterm infants and the estimated clearance rate was reported to be 0.0679 L.kg/h.

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.

Most of the administered dose is excreted in urine.

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).

Information regarding safety and efficacy in pregnancy and lactation is not available.