What should I discuss with my healthcare provider before taking meloxicam Mobic? In a six month target animal safety study, meloxicam was administered orally at 1, 3, and 5X the recommended dose with no significant clinical adverse reactions. All animals in all dose groups controls, 1, 3, and 5X the recommended dose exhibited some gastrointestinal distress diarrhea and vomiting. Treatment related changes seen in hematology and chemistry included decreased red blood cell counts in seven of 24 dogs four 3X and three 5X dogs decreased hematocrit in 18 of 24 dogs including three control dogs dose related neutrophilia in one 1X, two 3X and three 5X dogs, evidence of regenerative anemia in two 3X and one 5X dog. Also noted were increased BUN in two 5X dogs and decreased albumin in one 5X dog. brand cozaar zamienniki
Severe impairment or active liver disease: Use is contraindicated. There is limited experience with meloxicam overdosage. Cholestyramine is known to accelerate the clearance of meloxicam. Accelerated removal of meloxicam by 4 g oral doses of cholestyramine given three times a day was demonstrated in a clinical trial. Administration of cholestyramine may be useful following an overdosage. Serious stomach ulcers or bleeding can occur with the use of meloxicam suspension. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking meloxicam suspension with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling.
Maximum 15 mg daily. There are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. GI bleed compared to patients with neither of these risk factors.
As with other NSAIDs, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam. Meloxicam should not be given to patients with the aspirin triad. Consider potential benefits and risks of meloxicam therapy as well as alternative therapies before initiating therapy with the drug. Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
There is no evidence of statistically significant gender differences in drug pharmacokinetics. Drug bioavailability, volume of distribution, and total systemic clearance remain constant up to 5 times the recommended dose for use in dogs. However, there is some evidence of enhanced drug accumulation and terminal elimination half-life prolongation when dogs are dosed for 45 days or longer. Agitate the suspension well prior to administration of each dose. The other trademarks referenced are owned by third parties not affiliated with Boehringer Ingelheim Pharmaceuticals, Inc. Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. No dose adjustment is necessary in patients with mild to moderate renal impairment. Patients with severe renal impairment have not been studied. The use of meloxicam in subjects with severe renal impairment is not recommended. Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs NSAIDs. If combined, monitor patients extra closely for signs and symptoms of bleeding. Read the health information leaflet that accompanies the prescription as well as every time the prescription is refilled. There may be new health or medical information. Metabolized by CYP isoenzymes, mainly by CYP2C9 and to a lesser extent by CYP3A4. Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. The absolute bioavailability of meloxicam capsules was 89% following a single oral dose of 30 mg compared with 30 mg IV bolus injection. 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. The safe use of Metacam Oral Suspension in dogs younger than 6 months of age, dogs used for breeding, or in pregnant or lactating dogs has not been evaluated. Meloxicam is not recommended for use in dogs with bleeding disorders, as safety has not been established in dogs with these disorders. Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. AUC was unchanged. The time to maximum concentration T max was achieved between 5 and 6 hours. In comparison, neither the AUC nor the C max values for meloxicam suspension were affected following a similar high fat meal, while mean T max values were increased to approximately 7 hours. No pharmacokinetic interaction was detected with concomitant administration of antacids. Based on these results, meloxicam can be administered without regard to timing of meals or concomitant administration of antacids. Hemodialysis not dialyzable: Use with caution and monitor closely. Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Mobic, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Mobic, in women who have difficulties conceiving or who are undergoing investigation of infertility.
New onset or worsening of may occur. Increased risk of a heart attack or stroke that can lead to death. Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Meloxicam was not mutagenic in an Ames assay, or clastogenic in a chromosome aberration assay with human lymphocytes and an in vivo micronucleus test in mouse bone marrow. If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals. cilostazol
Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. Am J Med. Non-Steroidal Anti-Inflammatory Drugs NSAIDs? Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024. NSAIAs selective COX-2 inhibitors, prototypical NSAIAs may increase morbidity and mortality in patients with heart failure. Symptoms may include chest pain; decreased urination; loss of consciousness; seizures; severe dizziness, headache, or drowsiness; severe nausea, vomiting, or stomach pain; slow or troubled breathing; sluggishness; symptoms of liver problems eg, dark urine, loss of appetite, pale stools, severe stomach pain, yellowing of the skin or eyes; symptoms of stomach or bowel bleeding eg, bloody or black, tarry stools; vomit that looks like coffee grounds. Long-term administration of NSAIDs, including Mobic, has resulted in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. During concomitant use of Mobic and cyclosporine, monitor patients for signs of worsening renal function. See Table 3 for clinically significant drug interactions with meloxicam. Take meloxicam suspension by mouth. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems eg, bleeding, ulcers. Pharmaceuticals America, Inc. May, 2016. isoxsuprine buy online payment europe isoxsuprine
CycloSPORINE Systemic: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE Systemic. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE Systemic. CycloSPORINE Systemic may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents NSAIDs. Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects eg, hypertension during concomitant therapy with NSAIDs. Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, meloxicam should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma. Nonsteroidal anti-inflammatory drugs NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction MI and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk. Meloxicam pharmacokinetics have been investigated in subjects with mild and moderate renal impairment. Total drug plasma concentrations of meloxicam decreased and total clearance of meloxicam increased with the degree of renal impairment while free AUC values were similar in all groups. The higher meloxicam clearance in subjects with renal impairment may be due to increased fraction of unbound meloxicam which is available for hepatic metabolism and subsequent excretion. No dosage adjustment is necessary in patients with mild to moderate renal impairment. Patients with severe renal impairment have not been adequately studied. Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines. cheapest estreva purchase shopping
The use of meloxicam for the treatment of the signs and symptoms of rheumatoid arthritis was evaluated in a 12-week, double-blind, controlled multinational trial. Davies NM, Skjodt NM. Clinical pharmacokinetics of meloxicam; a cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug. Clin Pharmacokinet. RA is a type of arthritis that causes pain and swelling in the and small joints of the hand and feet. Fluid retention and edema have been observed in some patients taking NSAIDs. Use meloxicam with caution in patients with fluid retention, hypertension, or heart failure. Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs NSAIDs. If combined, monitor patients extra closely for signs and symptoms of bleeding. Food and Drug Administration. WebMD does not endorse any specific product, service, or treatment. Like bears coming out of hibernation, many of us are shaking off the winter rust and enjoying outdoor sports. Aspirin: When meloxicam is administered with aspirin 1000 mg three times daily to healthy volunteers, it tended to increase the AUC 10% and C max 24% of meloxicam. Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. During concomitant use of Mobic and lithium, monitor patients for signs of lithium toxicity. Category C. 1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.
NSAIDs should be considered. Cholestyramine is known to accelerate the clearance of meloxicam. During concomitant use of MOBIC and lithium, monitor patients for signs of lithium to xicity. The maximum amount of meloxicam for adults is 15 milligrams mg per day. Know the amount of meloxicam in the specific product you are taking. The pharmacological activity of Mobic in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections. Use of NSAIDs can be considered for the treatment of mild rheumatoid arthritis flares in pregnant women; however, use should be minimized or avoided early and late in pregnancy Bermas 2014; Saavedra Salinas 2015. ReoPro abciximab US prescribing information. Meloxicam is used to treat pain or inflammation caused by osteoarthritis or rheumatoid arthritis in adults and children who are at least 2 years old. No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs. 1 502 508 See Specific Drugs under Interactions. cheapest symbicort buy mastercard australia
Let your doctor know right away if you have any bleeding episodes or signs of bleeding. Mobic treatment groups in a 12-week placebo- and active-controlled osteoarthritis trial. Vicoprofen contains the same dose of ibuprofen as over-the-counter OTC NSAIDs, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuous use may increase the risk of heart attack or stroke. What happens if I miss a dose Mobic? B-adrenoreceptor-blockade therapy on blood pressure and the renin system in essential hypertension. Treating rheumatoid arthritis, osteoarthritis, and juvenile arthritis. It may also be used for other conditions as determined by your doctor. NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. Dogs with known hypersensitivity to meloxicam should not receive Metacam Oral Suspension. Do not use Metacam Oral Suspension in cats. Acute renal failure and death have been associated with the use of meloxicam in cats. Correct volume status in dehydrated or hypovolemic patients prior to initiating Mobic. Studies show the majority of sciatica sufferers respond to conservative treatment within a few weeks. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Mutagenesis: Meloxicam was not mutagenic in an Ames assay, or clastogenic in a chromosome aberration assay with human lymphocytes and an in vivo micronucleus test in mouse bone marrow. Do not consider WebMD User-generated content 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. purchase cheap phenazopyridine payment phenazopyridine
Young females exhibited slightly lower plasma concentrations relative to young males. Meloxicam suspension has an NSAID in it. Before you start any new medicine, check the label to see if it has an NSAID eg, ibuprofen in it too. If it does or if you are not sure, check with your doctor or pharmacist. This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation forming of a hole. These conditions can be fatal and can occur without warning while you are taking meloxicam, especially in older adults. The cause of the interaction is not known. Tell your doctor if your condition worsens. In vitro studies indicate that CYP2C9 cytochrome P450 metabolizing enzyme plays an important role in this metabolic pathway with a minor contribution of the CYP3A4 isozyme. Cimetidine: Concomitant administration of 200 mg cimetidine four times daily did not alter the single-dose pharmacokinetics of 30 mg meloxicam. Push the plunger to empty the contents of the syringe. NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Cymbalta duloxetine hydrochloride US prescribing information. Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Overdose symptoms may include nausea, vomiting, dizziness, drowsiness, black or bloody stools, coughing up blood, fever, urinating less than usual or not at all, shallow breathing, fainting, seizure convulsions or coma. Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of meloxicam with placebo. You can also ask them how many sessions you'll need. How Does Physical Therapy Treat Pain? Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops. What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs NSAIDs? caverta
To improve dosing accuracy in smaller weight children, the use of the Meloxicam Oral Suspension is recommended. The clinical relevance of this interaction has not been established. Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Sciatica often rears its ugly head when muscle imbalances are present. Tight, short muscles in the front of your thigh psoas, quadriceps can keep muscles in the back of your hips from properly doing their job. This scenario can cause an unbalanced tug-of-war between your weak and strong muscles, resulting in your spine not being supported efficiently. Osteoarthritis is a referred to as a because of the progressive decrease of surrounding the joints. Osteoarthritis is the most common chronic condition affecting the joints. Shake well before use then remove cap. Metacam Oral Suspension may be either mixed with food or placed directly into the mouth. Particular care should be given with regard to the accuracy of dosing. Metacam Oral Suspension can be given using the measuring syringe provided in the package see dosing procedure below.
No clinically important effect. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, NSAIDs, and aspirin all affect how platelets work to stop bleeding. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. Who should not take NSAIDs? Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. NSAIDs after a recent heart attack. Always provide client information sheet with prescription. Carefully consider the potential benefits and risk of Metacam and other treatment options before deciding to use Metacam. Use the lowest effective dose for the shortest duration consistent with individual response. Anemia may occur in patients receiving NSAIDs, including meloxicam. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including meloxicam, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. brand danocrine uk
NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. NSAIDs, including meloxicam, can cause serious gastrointestinal GI adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk. Pristiq desvenlafaxine succinate US prescribing information. Meloxicam is extensively metabolized in the liver. Meloxicam was approved for use in April 2000. This pharmacokinetic difference due to gender is likely to be of little clinical importance. There was linearity of pharmacokinetics and no appreciable difference in the C max or T max across genders. Meloxicam is extensively metabolized in the liver. Meloxicam metabolites include 5'-carboxy meloxicam 60% of dose from P-450 mediated metabolism formed by oxidation of an intermediate metabolite 5'-hydroxymethyl meloxicam which is also excreted to a lesser extent 9% of dose. In vitro studies indicate that CYP2C9 cytochrome P450 metabolizing enzyme plays an important role in this metabolic pathway with a minor contribution of the CYP3A4 isozyme. Cmax or Tmax across genders. No information is available from controlled clinical studies regarding the use of Mobic in patients with advanced renal disease. Avoid the use of Mobic in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome SJS and toxic epidermal necrolysis TEN; may occur without warning; discontinue use at first appearance of skin rash or any other sign of hypersensitivity. NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft CABG. vuli.info omeprazole
Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their healthcare provider. CYP2C9 Inhibitors Moderate: May decrease the metabolism of CYP2C9 Substrates. This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. Patients with severe renal impairment have not been studied. Information for Dog Owners: Metacam, like other drugs of its class, is not free from adverse reactions. Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with drug intolerance. Adverse reactions may include vomiting, diarrhea, decreased appetite, dark or tarry stools, increased water consumption, increased urination, pale gums due to anemia, yellowing of gums, skin or white of the eye due to jaundice, lethargy, incoordination, seizure, or behavioral changes. Serious adverse reactions associated with this drug class can occur without warning and in rare situations result in death see Adverse Reactions. Owners should be advised to discontinue Metacam and contact their veterinarian immediately if signs of intolerance are observed. NSAIDs that is written for health professionals. Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency. The opinions expressed in WebMD User-generated content areas like communities, reviews, ratings, or blogs 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. User-generated content areas 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. Meloxicam has nearly 100% bioavailability when administered orally with food. Keeping hip and back muscles strong and flexible may help keep sciatica from sidelining you. Foam rollers can also address muscle tightness by breaking up muscle adhesions aka “knots”. Not studied in patients with severe hepatic impairment Child-Pugh class III. lamisil
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The beneficial effects of your beta-blocker may decrease and cause an increase in your blood pressure. Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. For oral use in dogs only. Ross JR, Beeley L. Sulindac, prothrombin time, and anticoagulants. Vitamin K Antagonists eg, warfarin: NSAID Nonselective may enhance the anticoagulant effect of Vitamin K Antagonists. Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.
Long-term administration of NSAIDs, including meloxicam, can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Not all pack sizes may be marketed. The molecular weight is 351. Hosie J, Distel M, Bluhmki E. Meloxicam in osteoarthritis: a 6-month, double-blind comparison with diclofenac sodium. Br J Rheumatol.
What are Non-Steroidal Anti-Inflammatory Drugs NSAIDs? Meloxicam may also be used for purposes not listed in this medication guide. The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized, the drug is withdrawn, and veterinary care, if appropriate, is initiated. Owners should be advised of the importance of periodic follow up for all dogs during administration of any NSAID. Physical therapists are experts not only in treating pain but also its source. Yours will look for areas of weakness or stiffness that may be adding stress to the places that hurt. And they will treat those areas with certain exercises to reduce pain and help you move better.