Cognivel D

Cognivel D Uses, Dosage, Side Effects, Food Interaction and all others data.

Vitamin D is essential for normal bone growth and development and to maintain bone density. It is also necessary for utilization of both Calcium and Phosphorus. Vitamin D acts as a hormone and increases reabsorption of Calcium and Phosphorus by the kidneys and increased bone turnover.

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D . These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization . Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules . There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys . It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys .

Piracetam's mechanism of action is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as a sedative or stimulant. Piracetam is a positive allosteric modulator of the AMPA receptor. It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability. GABA brain metabolism and GABA receptors are not affected by piracetam

It has been found to increase blood flow and oxygen consumption in parts of the brain, but this may be a side effect of increased brain activity rather than a primary effect or mechanism of action for the drug.

Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes. Furthermore, piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains. Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria. But in the brain, it also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.

Piracetam is known to mediate various pharmacodynamic actions:

Neuronal effects:

Piracetam modulates the cholinergic, serotonergic, noradrenergic, and glutamatergic neurotransmission although the drug does not display high affinity to any of the associated receptors (Ki >10μM). Instead, piracetam increases the density of postsynaptic receptors and/or restore the function of these receptors through stabilizing the membrane fluidity . In the forebrain of aging mice, the density of NMDA receptors was increased by approximately 20% following 14 days of piracetam treatment. Based on the findings of various animal and human studies, the cognitive processses including learning, memory, attention and consciousness were enhanced from piracetam therapy without inducing sedation and psychostimulant effects . Piracetam mediate neuroprotective effects against hypoxia-induced damage, intoxication, and electroconvulsive therapy .

Vinpocetine increases cerebral metabolism; it increases glucose and O2 consumption; improves cerebral hypoxia tolerance; shifts glucose metabolism to the energetically more favourable aerobic pathway, but it increases the anaerobic pathway as well; it elevates the ATP concentration and the ATP/AMP ratio in the brain, and elevates the cerebral norepinephrine, dopamine and serotonin levels.

Vinpocetine considerably improves cerebral microcirculation by inhibiting platelet aggregation, reducing the pathologically increased blood viscosity, and increases erythrocyte deformability. It also promotes O2 transport into the tissues by reducing the O2 affinity of erythrocytes.

It selectively and intensely increases cerebral blood flow and the share of the brain in cardiac output, it reduces cerebral vascular resistance without affecting systemic circulation (blood pressure, heart rate, cardiac output, total peripheral resistance). It does not elicit steal phenomenon; on the contrary, it primarily improves the blood supply of the injured and ischaemic area while it remains unchanged in the intact areas (inverse steal effect). It further increases blood flow which is already increased as a result of hypoxia.

Cognivel D
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	Cognivel D
Generic	Betahistine Hcl + Cholecalciferol + Ginko Dry Extract + Piracetam + Vinpocetine
Type	Tablet
Therapeutic Class
Manufacturer	Linux Laboratories
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun.

Vitamin D with calcium is used to treat or prevent bone loss (osteoporosis). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth.

Cerebral vascular accidents and cerebral insufficiencies: Ischaemic or even haemorrhagic acute accidents, chronic manifestations of the above accidents or of cerebral atherosclerosis.

Mental retardation in children: Ease of resuming individual contact, sociability and learning, improved intellectual performances and school results.

Behaviour and psychotic problems in old age: Memory deficits, particularly with regard to fixation and evocation asthenia adaption disorders, disturbed psychomotor reactions. Patients suffering from myoclonus of cortical origin.

All forms of acute and chronic cerebral circulatory insufficiency: TIA (Transient Ischaemic Attack), reversible ischaemic neurological deficiency, progressive stroke, completed stroke, post-apoplectic conditions, multiinfarct dementia, cerebral arteriosclerosis, post-traumatic, hypertensive encephalopathy etc.

For the reduction of psychic or neurological symptoms of cerebral insufficiency (e.g., memory disturbances, dizziness, headache, aphasia, apraxia, locomotor disorders etc.).

Ophthalmology: It can be used for the treatment of vascular disorders of the choroid and retina due to arteriosclerosis, vasospasm, macular degeneration, arterial or venous thrombosis or embolism, and glaucoma secondary to the above mentioned disorders.

Otology: For the treatment of impaired hearing of vascular or toxic (iatrogenic) origin, presbyacusis, Meniere’s disease, cochleovestibular neuritis, tinnitus and dizziness of labyrinth origin.

For the treatment of vasovegetative symptoms of climacteric syndrome.For the treatment of vasovegetative symptoms of climacteric syndrome.

Cognivel D is also used to associated treatment for these conditions: Calcium and Vitamin D Deficiencies, Deficiency of Vitamin D3, Deficiency, Vitamin A, Deficiency, Vitamin D, Fracture Bone, Hip Fracture, Hypoparathyroidism, Hypophosphatemia, Familial, Menopause, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Vertebral Fractures, Vitamin D Resistant Rickets, Vitamin Deficiency, Severe Bone Resorption, Spine fracture, Calcium supplementation, Nutritional supplementation, Vitamin D Supplementation, Vitamin supplementationAlcohol Dependency, Alcohol Withdrawl, Cognitive Deficits caused by Injuries, Craniocerebral, Cognitive Dysfunctions, Cognitive Impairments, Comatose caused by Blood Vessel (Vascular) Dysfunction, Comatose caused by CNS Toxicity, Comatose caused by Traumas, Learning Disorders, Myoclonus, Sickle Cell Disease (SCD), Giddiness caused by Injuries, CraniocerebralCerebrovascular stenosis, Neurological Disorders

How Cognivel D works

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight .

Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease . Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone . Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus . This enhanced mobilization of skeletal calcium leads towards porotic bone conditions .

Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet . At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation . This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma .

In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively . Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts . Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels . Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys .

Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements . When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome . It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency . In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions .

Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity . Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide . The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion . This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function such as membrane transport, chemical secretion, and receptor binding and stimulation .

Through restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level . It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow .

Dosage

Cognivel D dosage

Oral solution: Colecalciferol (Vitamin D3) is recommended 5-10 mcg or 1-2ml (200-400 IU)/day or as directed by the physician.

Chewable tablet: Cholecalciferol (Vitamin D3) is recommended 100 IU (1 tablet) daily, or as directed by physician. Take the medicine with food or within 1 hour after a meal. Place the tablet in mouth swallow after chewing.

Injection:

Treatment of Cholecalciferol deficiency: 40,000 lU/week for 7 weeks, followed by maintenance therapy (1400-2000 lU/day). Follow-up 25 (OH) D measurements should be made approximately 3 to 4 months after initiating maintenance therapy to confirm that the target level has been achieved.
Prevention of Vitamin D deficiency: 20,000 lU/Month.
Treatment of Vitamin D deficiency:12-18 years: 20,000 IU, once every 2 weeks for 6 weeks. Prevention of Vitamin D deficiency, 12-18 years: 20,000 IU, once every 6 weeks.

Oral: Adults:

In cerebro-cortical insufficiency disorders, usual dose is one tablet (800 mg) 3 times a day.
In myoclonic seizures, a dose of 7.2 gm daily, increasing by 4.8 gm per day every 3 to 4 days up to maximum of 20 gm daily, given in 2 or 3 divided doses.

Oral: Children:

The daily dosage depends on the weight of the child, 50 mg/kg of body weight in 3 divided doses. Once the desired results has been obtained, reduce the initial dose by half.

Parenteral formulations: When parenteral administration is needed (e.g. swallowing difficulties, unconsciousness) Piracetam can be administered intravenously.When treating severe symptoms, 12 g daily may need to be administered as an intravenous infusion.

Vinpocetine is taken 15-30 mg daily in 3 divided doseswith meals. The maintenance dose is 15 mg three times daily over long periods.

Piracetam is compatible (physico-chemical compatibility) with the perfusions of:

Glucose 5%, 10%, 20%
Fructose 5%, 10%, 20%
Sodium chloride 0.9%
Dextran 40 (10% in a 0.9% NaCl solution)
Ringer Mannitol 20%
HES solution (Hydroxy Ethyl Starch) 6% and 10%

The stability of these solutions has been demonstrated up to 24 hours.

Side Effects

Generally all nutritional supplements are considered to be safe and well tolerable. However, few side-effects can generally occur including hypercalcaemia syndrome or Calcium intoxication (depending on the severity and duration of hypercalcaemia), occasional acute symptoms include anorexia, headache, nausea, vomiting, abdominal pain or stomach ache and constipation with the administration of Colecaciferol.

The side effects reported include nervousness, agitation, irritability, anxiety and sleep disturbances. The incidence of these during clinical trials was (≤ 5%) and they were more often noted in the older patients taking > 2.4 gm daily. In the majority of cases, a dose reduction sufficed to make these symptoms disappear. Some patients may complain of fatigue or drowsiness, gastrointestinal problems, e.g. nausea, vomiting, diarrhoea and stomachache have also been reported but their incidence during clinical trials was ≤ 2%. Other symptoms e.g. vertigo, headache, trembling and sexual stimulation have occasionally been reported.

Vinpocetine is well tolerated. In some cases transient fall of blood pressure and tachycardia may occur.

Toxicity

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae . Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia . Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures .

Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established . Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus, and other effects . Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures .

Vitamin D is deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of Vitamin D3 in excess of 10 µg daily should not be administered daily to nursing women.

The cases of overdose with piracetam is rare. The highest reported overdose with piracetam was oral intake of 75g which was associated with diarrhea and abdominal pain; the signs were most likely related to the extreme high dose of sorbitol contained in the used formulation. In cases of acute, significant overdosage, stomach emptying by gastric lavage or induced emesis is recommended as there are no known antidotes for piracetam . Management for an overdose will most likely be symptomatic treatment and may include hemodialysis, where the extraction efficacy of the dialyser is 50 to 60% for the drug .

Oral LD50 in a mouse acute toxicity study was 2000 mg/kg .

Precaution

People with the following conditions should exercise caution when considering taking vitamin D supplements: High blood Calcium or Phosphorus level, Heart problems, Kidney disease.

Vitamin D must be taken with adequate amounts of both Calcium and Magnesium supplementation. When Calcium level is low (due to insufficient vitamin D and calcium intake), the body activates the parathyroid gland, which produces PTH (parathyroid hormone). This hormone kick starts vitamin D hormone production and assists removal of Calcium from the bones to be used in more important functions such as neutralizing body acidity.

Because Vinpocetine can reduce the ability of blood to clot, those individuals with a tendency to bleed should avoid Vinpocetine.

Interaction

Cholecalciferol is known to interact with Carbamazepine, Dactinomycin, Diuretics, Fosphenytoin, Miconazole, Phenobarbital, Phenytoin, Primidone

In a single case, confusion, irritability and sleep disorders were reported in concomitant use with thyroid extract. At present, no interaction has been observed with the following anti-epileptic drugs, clonazepam, carbamazepine, phenyton, phenobarbitone and sodium valporate, based on a small number of studies.

Slight changes in prothrombin time have been noted in those adding Vinpocetine to Warfarin dosing. The changes appear minimal. There are no other interactions reported so far. Therefore, it can be applied in combinations.

Volume of Distribution

Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L .

Vd is approximately 0.6L/kg. Piracetam may cross the blood-brain barrier as it was measured in the cerebrospinal fluid following intravenous administration . Piracetam diffuses to all tissues except adipose tissues, crosses placental barrier and penetrates the membranes of isolated red blood cells .

Elimination Route

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal . Moreover, bile is necessary for absorption as well .

In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol .

Piracetam displays a linear and time-dependent pharmacokinetic properties with low intersubject variability over a large range of doses. Piracetam is rapidly and extensively absorbed following oral administration with the peak plasma concentration is reached within 1 hour after dosing in fasted subjects. Following a single oral dose of 3.2 g piracetam, the peak plasma concentration (Cmax) was 84 µg/mL. Intake of food may decrease the Cmax by 17% and increase the time to reach Cmax (Tmax) from 1 to 1.5 hours. Tmax in the cerebrospinal fluid is achieved approximately 5 hours post-administration .

The absolute bioavailability of piracetam oral formulations is close to 100% and the steady state plasma concentrations are achieved within 3 days of dosing .

Half Life

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days .

Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals .

The plasma half life of piracetam is approximately 5 hours following oral or intravenous administration. The half life in the cerebrospinal fluid was 8.5 hours .

Clearance

Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day .

The apparent total body clearance is 80-90 mL/min .

Elimination Route

It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces .

Piracetam is predominantly excreted via renal elimination, where about 80-100% of the total dose is recovered in the urine. Approximately 90% of the dose of piracetam is excreted in the urine as unchanged drug .

Pregnancy & Breastfeeding use

There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses. Colecalciferol should be used during pregnancy only if the benefits outweigh the potential risk to the fetus.

It should be assumed that exogenous Colecalciferol passes into the breast milk. In view of the potential for hypercalcaemia in the mother and for adverse reactions from Colecalciferol in nursing infants, mothers may breastfeed while taking Colecalciferol, provided that the serum Calcium levels of the mother and infant are monitored.

Piracetam should not be prescribed during pregnancy or when breast feeding, except under exceptional circumstances. Piracetam is able to cross the placenta.

Pregnancy category- Not classified

Contraindication

Colecalciferol is contraindicated in all diseases associated with hypercalcaemia. It is also contraindicated in patients with known hypersensitivity to Colecalciferol (or medicines of the same class) and any of the constituent excipients. Colecalciferol is contraindicated if there is evidence of vitamin D toxicity.

Piracetam is contra-indicated in patients with severe renal insufficiency (creatinine clearance < 20 ml/min) and hepatic impairment. As the principal route of elimination for Piracetam is via the kidney, special care must be taken when treating patients known to suffer from renal insufficiency. Monitoring of renal function is recommended in such cases. The increase in half-life is directly related to the decrease in renal function and creatinine clearance. This is also true for the older patient in whom creatinine clearance is dependent on age. When the creatinine clearance is < 60 ml/min, or serum creatinine is >1.25 mg/100 ml, the dosage prescribed should be calculated as following:

CrCl 60-40 ml/min: Dosage should be 1/2 of normal dose

CrCl 40-20 ml/min: Dosage should be 1/4 of normal dose

Vinpocetine is contraindicated in pregnancy and lactation. Hypersensitivity to its components is also contraindicated.

Special Warning

Children: No formal pharmacokinetic study has been conducted in children.

Elderly: In the elderly, the half-life of piracetam is increased and the increase is related to the decrease in renal function in this population (see Section Dosage and Administration).

Renal impairment: Piracetam clearance is correlated to creatinine clearance. It is therefore recommended to adjust the daily dose of piracetam based on creatinine clearance in patients with renal impairment

Hepatic impairment: The influence of hepatic impairment on the pharmacokinetics of piracetam has not been evaluated. Because 80 to 100% of the dose is excreted in the urine as unchanged drug, hepatic impairment solely would not be expected to have a significant effect on piracetam elimination.

Acute Overdose

Symptoms: anorexia, headache, vomiting, constipation, dystrophy (weakness, loss of weight), sensory disturbances, possibly fever with thirst, polyuria, dehydration, apathy, arrested growth and urinary tract infections. Hypercalcaemia ensues, with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.

Treatment: Immediate gastric lavage or induction of vomiting to prevent further absorption. Liquid paraffin should be administered to promote faecal excretion. Repeated serum calcium determinations are advisable. If elevated calcium levels persist in the serum, phosphates and corticosteroids may be administered and measures instituted to bring about adequate diuresis.

Piracetam appears to be devoid of toxicity even at very high doses and, therefore, the need for specific measures to be taken in case of an overdose is avoided. Drug Interactions: In a single case, confusion, irritability and sleep disorders were reported in concomitant use with thyroid extract. At present, no interaction has been observed with the following anti-epileptic drugs, clonazepam, carbamazepine, phenytoin, phenobarbitone and sodium valproate, based on a small number of studies.