Side effects may go away after you take the medicine for a while. Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When Depakote ER is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. order now online pantozol pills pantozol
Chemically it is designated as sodium bis2-propylpentanoate. Caution should be observed when administering valproate products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. See below, “Patients with Known or Suspected Mitochondrial Disease. If you are able to become pregnant, you must use an effective form of birth control while you take Depakote ER extended-release tablets. Contact your doctor right away if you become pregnant or think you may be pregnant while taking Depakote ER extended-release tablets.
Children younger than 2 years old have an increased risk of fatal liver problems, especially if they take more than 1 seizure medicine or have a metabolic disorder, a severe seizure disorder along with mental retardation, or organic brain disease. Discuss any questions or concerns with your doctor. Children within the first two months of life have a markedly decreased ability to eliminate valproate compared to older children and adults. This is a result of reduced clearance perhaps due to delay in development of glucuronosyltransferase and other enzyme systems involved in valproate elimination as well as increased volume of distribution in part due to decreased plasma protein binding. For example, in one study, the half-life in children under 10 days ranged from 10 to 67 hours compared to a range of 7 to 13 hours in children greater than 2 months.
Check with your pharmacist about how to dispose of unused medicine. Fortunately, many women with the financial resources or support from their employers can work from bed using a portable computer and telephone, for example. The maximum time between doses in the three times a day schedule should not exceed 12 hours. What other drugs will affect gabapentin? Depakote ER or placebo and treated for 12 weeks.
The results of two multicenter, randomized, double-blind, placebo-controlled clinical trials established the effectiveness of Depakote in the prophylactic treatment of migraine headache. Don't stop taking your medicine without your doctor's permission. As of 2016 it is also registered for 45 phase II clinical trials some completed for various cancers. Depakote Sprinkle Capsules are for oral administration. Depakote Sprinkle Capsules contain specially coated particles of divalproex sodium equivalent to 125 mg of valproic acid in a hard gelatin capsule. Depakote ER, Depakote should be used instead. SCE frequencies may be associated with epilepsy. What is valproic acid, and how does it work mechanism of action? Gralise R is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. There may be other side effects that you experience that are not described above. This article is meant to be educational and is not meant to be all-inclusive or to replace information provided by your doctor. To govern infection, we need to apprehend what is causing it within the first place. While the elements contributing to infection appear complicated, the main things to recollect are two: digestive health and mental fitness. Nervous System: Abnormal dreams, abnormal gait, agitation, ataxia, catatonic reaction, confusion, depression, diplopia, dysarthria, hallucinations, hypertonia, hypokinesia, insomnia, paresthesia, reflexes increased, tardive dyskinesia, thinking abnormalities, vertigo. Inflammation of the pancreas is a potentially life-threatening illness associated with Depakote ER extended-release tablets. Symptoms include stomach pain, vomiting, or loss of appetite. Contact your doctor at once if any of these symptoms occur.
There may be other medicines to treat your condition that have a lower chance of causing birth defects and decreased IQ in your child. Do not stop taking Depakote or Depakene without first talking to your healthcare provider. Stopping Depakote or Depakene suddenly can cause serious problems. Regardless of what happens, you should let your doctor know that you had an episode of angina. If this is unusual for you, if your angina episodes are occurring more frequently or lasting longer, or if you need more medicine to control them, tell your doctor. Valproate causes birth defects; exposure during is associated with about three times as many major abnormalities as usual, mainly with the risks being related to the strength of medication used and use of more than one drug. More rarely, with several other defects, possibly including a "valproate syndrome". Reproductive: Aspermia, azoospermia, decreased sperm count, decreased spermatozoa motility, male infertility, and abnormal spermatozoa morphology. The primary findings were an increase in the incidence of subcutaneous fibrosarcomas in high-dose male rats receiving valproate and a dose-related trend for benign pulmonary adenomas in male mice receiving valproate. The significance of these findings for humans is unknown. This is compared to a rate of 5% for the 81 placebo patients. The maximum time between doses in the three times a day schedule should not exceed 12 hours. There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during Depakote treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of Depakote in such longer-term treatment. Although there are no efficacy data that specifically address longer-term antimanic treatment with Depakote, the safety of Depakote in long-term use is supported by data from record reviews involving approximately 360 patients treated with Depakote for greater than 3 months. Depakote ER is a valproate and is indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. A mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode depressed mood, loss of interest or pleasure in nearly all activities. Divalproex sodium does not relieve acute migraine headaches. Prepare the inhalation solution right before use. Discard any unused solution after 24 hours. Do not store for longer periods. Ask your professional for details. You may also feel a burning sensation under your tongue. aprovel
Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. 'Multum' is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Depakote tablets are administered orally. The recommended starting dose is 250 mg twice daily. Primidone, which is metabolized to a barbiturate, may be involved in a similar interaction with valproate. NEAD study: a prospective observational study. Do not stop Depakote or Depakene without first talking to a healthcare provider. Stopping Depakote or Depakene suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop status epilepticus. Death AK, McGrath KC, Handelsman DJ 2005. "Valproate is an anti-androgen and anti-progestin". Steroids. Experience employing dosing regimens from once-a-day to four-times-a-day, as well as studies in primate epilepsy models involving constant rate infusion, indicate that total daily systemic bioavailability extent of absorption is the primary determinant of seizure control and that differences in the ratios of plasma peak to trough concentrations between valproate formulations are inconsequential from a practical clinical standpoint. Tell your doctor or dentist that you take Depakote delayed-release tablets before you receive any medical or dental care, emergency care, or surgery. Figure 2 presents the proportion of patients X axis whose percentage reduction from baseline in complex partial seizure rates was at least as great as that indicated on the Y axis in the adjunctive therapy study. Depakote delayed-release tablets may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Depakote delayed-release tablets with caution. Counsel patients, their caregivers, and families that AEDs, including Depakote ER, may increase the risk of suicidal thoughts and behavior and to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Depakote ER extended-release tablets has been shown to cause harm to the fetus. If you may become pregnant, discuss other possible treatment options with your doctor. If a decision is made to take Depakote ER extended-release tablets, use effective birth control while you are taking it. Talk with your doctor if you are planning to become pregnant, or if you have questions or concerns about this information.
John M. Pellock, MD, spokesman for the American Society and chairman of child neurology at Virginia Commonwealth University. "Get and stay healthy. In animal studies, offspring with prenatal exposure to valproate had structural malformations similar to those seen in humans and demonstrated neurobehavioral deficits. Hurley, founder and executive director of Sidelines National Support Network, a resource for women and families who are experiencing complicated pregnancies. The mechanism of this interaction in not well understood. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during Depakote ER treatment of an acute manic episode. purchase apetamin-p high
RxList is part of the WebMD Health Network. The opinions expressed in the WebMD User Reviews are solely those of the User, who may or may not have medical or scientific training, and do not represent the opinions of WebMD. These member reviews have not been reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other purpose except for compliance with our Terms and Conditions. Depakote ER extended-release tablets may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Depakote ER extended-release tablets with caution. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor. Depakote and Depakene can cause drowsiness and dizziness. GABA by neuronal cells. Body as a Whole: Accidental injury, viral infection. Controlling certain types of seizures in the treatment of epilepsy. It is also used to treat the manic phase of bipolar disorder manic-depressive illness and prevent migraine headaches. It may also be used for other conditions as determined by your doctor. Depakote Sprinkle Capsules are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. Depakote Sprinkle Capsules are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures. Sotaniemi K 1982. "Valproic acid in the treatment of nonepileptic myoclonus". Arch. Neurol. Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate. The elimination half-life of diazepam remained unchanged upon addition of valproate. Depakote delayed-release tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people.
Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, depression, or if you feel agitated, hostile, restless, hyperactive mentally or physically or have thoughts about suicide or hurting yourself. The following adverse reactions occurred in greater than 5% of Depakote ER-treated patients and at a greater incidence for placebo than for Depakote ER: asthenia and flu syndrome. Nervous System: Abnormal dreams, amnesia, confusion, depression, emotional lability, insomnia, nervousness, paresthesia, speech disorder, thinking abnormalities, and vertigo. Plasma valproate C min concentrations for DEPAKOTE ER on average are equivalent to DEPAKOTE, but may vary across patients after conversion. Effective Dose: reached by upward titration over a period of approximately 3 days. In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Matsuoka M, Igisu H 1993. "Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia". Biochem. Pharmacol. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M 2013. The recommended dosage is 600 mg orally twice daily. This drug is available at a higher level co-pay. Lonergan E, Luxenberg J 2009. PDF. Cochrane Database Syst Rev 3: CD003945. Divalproex sodium can cause liver failure that may be fatal, especially in children under age 2 and in people with liver problems caused by a genetic mitochondrial disorder. Do not consider Communities as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare provider because of something you have read on WebMD. You should always speak with your doctor before you start, stop, or change any prescribed part of your care plan or treatment. WebMD understands that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified health care provider. If you think you may have a medical emergency, call your doctor or dial 911 immediately. fenofibrate online purchase now
Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment. In general, you should call your doctor if any new symptoms occur or if you notice side effects from your medication. Mood stabilizers balance certain chemicals that control emotional states and behavior. Luat, AF 20 September 2007. "Paroxysmal tonic upgaze of childhood with co-existent absence epilepsy. Depakote ER is indicated for prophylaxis of migraine headaches in adults. Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. For the best possible benefit, it is important to receive each scheduled dose of this as directed. If you miss an injection, contact your doctor or right away to establish a new dosing schedule. No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. In a case review study of 583 patients, 72 patients 12% were greater than 65 years of age. A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. Discontinuation of valproate was occasionally associated with the latter two events. It is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. When using delayed-release tablets, total daily doses in excess of 250 mg should be given in divided doses. You may open the divalproex sodium sprinkle capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow this mixture right away. Depakote divalproex sodium delayed release tablets for this indication. P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation. The maximum time interval between doses should not exceed 12 hours. Depakote ER divalproex sodium extended-release tablets are administered orally, and must be swallowed whole.
Multiple subpial transection MST is a surgery used to control brain seizures in people with epilepsy who don't respond to medication. Ask your health care provider any questions you may have about how to use Depakote delayed-release tablets. Depakote ER-treated group was greater than 5% and was greater than that for placebo patients. Get emergency medical help if you have signs of an allergic reaction to gabapentin: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Depakote ER 500 mg is available as gray ovaloid tablets with the “a” logo and the code HC. Each Depakote ER tablet contains divalproex sodium equivalent to 500 mg of valproic acid. Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes. Depakote delayed-release tablets may cause an unusual drop in body temperature hypothermia. Symptoms may include confusion, lack of energy, loss of coordination, shivering, slow heartbeat, slow or shallow breathing, slurred speech, or unusual drowsiness. Contact your doctor right away if you have any of these symptoms. When he examined her, he found that her was 80% effaced thinned out -- a sign of early labor and she was having that lasted about 100 seconds and were spaced only five minutes apart. She went on from that moment on and remained in bed for 14 weeks until her water broke. Then she went to the hospital for delivery. Valproate can cause decreased IQ scores in children whose mothers were treated with valproate during pregnancy. armidex
These medicines are available in syrup, tablet, capsule, and chewable tablet forms. Bentley, Suzanne Dec 11, 2013. Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Valproate is excreted in human milk. Diabetes patients - Depakote ER extended-release tablets may cause the results of some tests for urine ketones to be wrong. Ask your doctor before you change your diet or the dose of your diabetes medicine. Inform pregnant women and women of childbearing potential that use of valproate during pregnancy increases the risk of birth defects and decreased IQ in children who were exposed. Advise women to use effective contraception while using valproate. When appropriate, counsel these patients about alternative therapeutic options. This is particularly important when valproate use is considered for a condition not usually associated with permanent injury or death.
There have been reports of acute or subacute encephalopathy in the absence of elevated ammonia levels, elevated valproate levels, or neuroimaging changes. The encephalopathy reversed partially or fully after valproate discontinuation. Depakote delayed-release tablets comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Depakote delayed-release tablets refilled. Hicks CW, Pandya MM, Itin I, Fernandez HH 2011. "Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease". Parkinsonism Relat. Disord. Special Senses: Hearing loss. For colistimethate injection, consult the product instructions and your for storage details. Depakote ER 250 and 500 mg tablets are for oral administration. Depakote ER tablets contain divalproex sodium in a once-a-day extended-release formulation equivalent to 250 and 500 mg of valproic acid. order cheapest irbesartan shopping europe
Depakote is contraindicated in patients with known urea cycle disorders UCD. Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of Depakote therapy, evaluation for UCD should be considered in the following patients: 1 those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2 those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3 those with a family history of UCD or a family history of unexplained infant deaths particularly males; 4 those with other signs or symptoms of UCD. Take an active role. You need to be more than a patient. We're 2000 miles apart in a long-distance relation. I'm a busy professional also. I plan to visit him at a break in a week. Perhaps I need to drag him to see a doctor? Carbapenem antibiotics for example, ertapenem, imipenem, meropenem; this is not a complete list may reduce serum valproate concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproate concentrations should be monitored frequently after initiating carbapenem therapy. Note Depakene capsules are valproic acid. Long-acting forms of nitroglycerin are used to prevent angina from happening. They are not used to stop sudden symptoms of angina. These long-acting forms include pills, tablets, ointment, and skin patches. This topic does not cover these long-acting forms of nitroglycerin. Depakote ER-treated group was greater than 5% and greater than the placebo incidence. If you take too much Depakote or Depakene, call your healthcare provider or local Poison Control Center right away. Some MEDICINES MAY INTERACT with Depakote delayed-release tablets. Therefore, healthcare providers who elect to use Depakote ER for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient. Based on a population pharmacokinetic analysis, rufinamide clearance was decreased by valproate. Metabolic and Nutritional Disorders: Hypoproteinemia, Peripheral Edema.
Titration: The dose should be rapidly titrated to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. Do not take the erection-enhancing medicine sildenafil Viagra tadalafil or vardenafil if you are taking nitroglycerin. Combining nitroglycerin with any of these medicines can cause a life-threatening drop in blood pressure. If you have angina and have taken one of these erection-enhancing medicines, be sure to tell your doctor so that you are not given nitroglycerin or another nitrate medicine. Metabolism and nutrition: Weight gain. Special Senses: Amblyopia, conjunctivitis, deafness, dry eyes, ear pain, eye pain, tinnitus. Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose. What happens if I overdose? Before having surgery or any procedure requiring anesthesia or that block nerve or muscle activity, tell your doctor or dentist that you are using this medication. Body as a Whole: Back pain, chest pain, malaise. Avoid taking an antacid within 2 hours before or after you take gabapentin. Antacids can make it harder for your body to absorb gabapentin. Wyllie E, Cascino GD, Gidal BE, Goodkin HP 17 February 2012. Respiratory System: Dyspnea, and sinusitis. Cardiovascular System: Hypertension, hypotension, palpitations, postural hypotension, tachycardia, vasodilation. Depakote ER 250 mg is available as white ovaloid tablets with the “a” logo and the code HF. Each Depakote ER tablet contains divalproex sodium equivalent to 250 mg of valproic acid. What are Depakote and Depakene? Miles MV, Snead OC 3rd, Thorn MD. Predictability of unbound antiepileptic drug concentrations in children treated with valproic acid and phenytoin. Please speak to your therapist as soon as possible. You deserve to live life for YOU, not for the prospect that someone will one day come back to you. Nurture yourself. Love yourself. We are here for you. This information should not be used to decide whether or not to take Depakote delayed-release tablets or any other medicine. Only your health care provider has the knowledge and training to decide which medicines are right for you. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Depakote delayed-release tablets. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Depakote delayed-release tablets. This information is not specific medical advice and does not replace information you receive from your health care provider. You must talk with your health care provider for complete information about the risks and benefits of using Depakote delayed-release tablets. arvut.info risperdal
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Due to an increased risk for liver problems, people with certain inherited metabolic disorders such as Alpers-Huttenlocher syndrome should not use this medication. Children younger than 2 years who might have these disorders should not use this medication. Children older than 2 years who might have these disorders should be closely monitored during treatment with divalproex sodium. Talk to your doctor for details. For sudden episodes of angina, use nitroglycerin in a tablet or liquid spray form. Behaviors of concern should be reported immediately to healthcare providers. The opinions expressed in WebMD Communities are solely those of the User, who may or may not have medical or scientific training. These opinions do not represent the opinions of WebMD. Communities are not reviewed by a WebMD physician or any member of the WebMD editorial staff for accuracy, balance, objectivity, or any other reason except for compliance with our Terms and Conditions.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your or local waste disposal company. Do not start, stop, or change the dosage of any medicines without your doctor's approval. Contact your doctor or health care provider right away if any of these apply to you. To answer your question, the drop from 140 down to 60 mgs of methadone is whats causing ur withdrawal symptoms not the lithium. Respiratory System: Sinusitis, cough increased, pneumonia, epistaxis.
Also, tell your doctor about other drugs, vitamins, and you take. when you are taking an epilepsy medication. The capacity of elderly patients age range: 68 to 89 years to eliminate valproate has been shown to be reduced compared to younger adults age range: 22 to 26 years. Intrinsic clearance is reduced by 39%; the free fraction is increased by 44%. Hepatic failure resulting in fatalities has occurred in patients receiving valproate. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months of valproate therapy. However, healthcare providers should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.
Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take. Depakote tablets are for oral administration. Remember that your doctor has prescribed this because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication not have serious side effects.