DRUGS & SUPPLEMENTS

Vabra-TZ

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Vabra-TZ uses

Vabra-TZ consists of Tizanidine, Valdecoxib.

Tizanidine:


Vabra-TZ (Tizanidine) is a short-acting drug for the management of spasticity. Vabra-TZ (Tizanidine) is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, Vabra-TZ (Tizanidine) has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of Vabra-TZ (Tizanidine) are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.

Indication: For the management of increased muscle tone associated with spasticity

Valdecoxib:


INDICATIONS AND USAGE

Vabra-TZ (Valdecoxib) Tablets are indicated:

  • For relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis.
  • For the treatment of primary dysmenorrhea.

CONTRAINDICATIONS

Vabra-TZ (Valdecoxib) should not be given to patients who have demonstrated allergic-type reactions to sulfonamides.

Vabra-TZ (Valdecoxib) Tablets are contraindicated in patients with known hypersensitivity to Vabra-TZ (Valdecoxib). Vabra-TZ (Valdecoxib) should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs are possible in such patients. BEXTRA is contraindicated for the treatment of post-operative pain immediately following coronary artery bypass graft (CABG) surgery and should not be used in this setting..

WARNINGS

Gastrointestinal Effects — Risk of GI Ulceration, Bleeding, and Perforation

Serious gastrointestinal toxicity such as bleeding, ulceration and perforation of the stomach, small intestine or large intestine can occur at any time with or without warning symptoms in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor gastrointestinal problems such as dyspepsia are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding even in the absence of previous GI tract symptoms. Patients should be informed about the signs and symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation caused by NSAIDs appear to occur in approximately 1% of patients treated for 3 to 6 months and 2–4% of patients treated for one year. These trends continue, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Studies have shown that patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease, pharmacoepidemiological studies have identified several other co-therapies or co-morbid conditions that may increase the risk for GI bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status.

Serious Skin Reactions

Vabra-TZ contains a sulfonamide moiety and patients with a known history of a sulfonamide allergy may be at a greater risk of skin reactions. Patients without a history of sulfonamide allergy may also be at risk for serious skin reactions.

Serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported through postmarketing surveillance in patients receiving Vabra-TZ (Valdecoxib). Fatalities due to Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Patients appear to be at higher risk for these events early in the course of therapy, with the onset of the event occurring in the majority of cases within the first two weeks of treatment. Vabra-TZ (Valdecoxib) should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Serious skin reactions have been reported with other COX-2 inhibitors during postmarketing experience. The reported rate of these events appears to be greater for Vabra-TZ (Valdecoxib) as compared to other COX-2 agents.

Anaphylactoid Reactions

In postmarketing experience, cases of hypersensitivity reactions (anaphylactic reactions and angioedema) have been reported in patients receiving Vabra-TZ (Valdecoxib). These cases have occurred in patients with and without a history of allergic-type reactions to sulfonamides. Vabra-TZ (Valdecoxib) should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Coronary Artery Bypass Graft Surgery

Patients treated with Vabra-TZ for pain following coronary artery bypass graft surgery have a higher risk for cardiovascular/thromboembolic events, deep surgical infections or sternal wound complications. Vabra-TZ (Valdecoxib) is therefore contraindicated for the treatment of postoperative pain following CABG surgery. .

Advanced Renal Disease

No information is available regarding the safe use of Vabra-TZ (Valdecoxib) Tablets in patients with advanced kidney disease. Therefore, treatment with Vabra-TZ (Valdecoxib) is not recommended in these patients. If therapy with Vabra-TZ (Valdecoxib) must be initiated, close monitoring of the patient's kidney function is advisable.

Pregnancy

In late pregnancy, Vabra-TZ (Valdecoxib) should be avoided because it may cause premature closure of the ductus arteriosus.

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PRECAUTIONS

General

Vabra-TZ Tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of Vabra-TZ (Valdecoxib) in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. These laboratory abnormalities may progress, may remain unchanged, or may remain transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure (some with fatal outcome) have been reported with NSAIDs. In controlled clinical trials of Vabra-TZ (Valdecoxib), the incidence of borderline (defined as 1.2- to 3.0-fold) elevations of liver tests was 8.0% for Vabra-TZ (Valdecoxib) and 8.4% for placebo, while approximately 0.3% of patients taking Vabra-TZ (Valdecoxib), and 0.2% of patients taking placebo, had notable (defined as greater than 3-fold) elevations of ALT or AST.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with Vabra-TZ (Valdecoxib). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), Vabra-TZ (Valdecoxib) should be discontinued.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis 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 and Angiotensin Converting Enzyme inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Caution should be used when initiating treatment with Vabra-TZ (Valdecoxib) in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with Vabra-TZ (Valdecoxib). Caution is also recommended in patients with preexisting kidney disease.

Hematological Effects

Anemia is sometimes seen in patients receiving Vabra-TZ (Valdecoxib). Patients on long-term treatment with Vabra-TZ (Valdecoxib) should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

Vabra-TZ (Valdecoxib) does not generally affect platelet counts, prothrombin time (PT), or activated partial thromboplastin time (APTT), and does not appear to inhibit platelet aggregation at indicated dosages.

Fluid Retention and Edema

Fluid retention and edema have been observed in some patients taking Vabra-TZ. Therefore, Vabra-TZ (Valdecoxib) should be used with caution in patients with fluid retention, hypertension, or heart failure.

Preexisting Asthma

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 nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Vabra-TZ (Valdecoxib) should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Vabra-TZ can cause GI discomfort and, rarely, more serious GI side effects, which may result in hospitalization and even fatal outcomes. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up Effects — Risk of GI Ulceration, Bleeding, and Perforation).

Patients should report to their physicians, signs or symptoms of gastrointestinal ulceration or bleeding, weight gain, or edema. Patients should be instructed to discontinue treatment and seek medical attention at the first signs of a skin reaction (pruritus, rash, erythema, or mucosal lesions).Patients should also be instructed to seek immediate emergency help in the case of an anaphylactoid reaction. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical attention. In late pregnancy, Vabra-TZ (Valdecoxib) should be avoided because it may cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs and symptoms of GI bleeding.

Drug Interactions

The drug interaction studies with Vabra-TZ were performed both with Vabra-TZ (Valdecoxib) and a rapidly hydrolyzed intravenous prodrug form. The results from trials using the intravenous prodrug are reported in this section as they relate to the role of Vabra-TZ (Valdecoxib) in drug interactions.

General

In humans, Vabra-TZ (Valdecoxib) metabolism is predominantly mediated via CYP 3A4 and 2C9 with glucuronidation being a further (20%) route of metabolism. In vitro studies indicate that Vabra-TZ (Valdecoxib) is a moderate inhibitor of CYP 2C19 (IC50 = 6 µg/mL or 19 µM) and 2C9 (IC50 = 13 µg/mL or 41 µM), and a weak inhibitor of CYP 2D6 (IC50 = 31 µg/mL or 100 µM) and 3A4 (IC50 = 44 µg/mL or 141 µM).

Aspirin

Concomitant administration of aspirin with Vabra-TZ may result in an increased risk of GI ulceration and complications compared to Vabra-TZ (Valdecoxib) alone. Because of its lack of anti-platelet effect Vabra-TZ (Valdecoxib) is not a substitute for aspirin for cardiovascular prophylaxis.

In a parallel group drug interaction study comparing the intravenous prodrug form of Vabra-TZ (Valdecoxib) at 40 mg BID (n=10) vs placebo (n=9), Vabra-TZ (Valdecoxib) had no effect on in vitro aspirin-mediated inhibition of arachidonate- or collagen-stimulated platelet aggregation.

Methotrexate

Vabra-TZ (Valdecoxib) 10 mg BID did not show a significant effect on the plasma exposure or renal clearance of methotrexate.

ACE-inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking Vabra-TZ concomitantly with ACE-inhibitors.

Furosemide

Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

Anticonvulsants

Steady state plasma exposure (AUC) of Vabra-TZ (Valdecoxib) (40 mg BID for 12 days) was decreased by 27% when coadministered with multiple doses (300 mg QD for 12 days) of phenytoin (a CYP 3A4 inducer). Patients already stabilized on Vabra-TZ (Valdecoxib) should be closely monitored for loss of symptom control with phenytoin coadministration. Vabra-TZ (Valdecoxib) did not have a statistically significant effect on the pharmacokinetics of phenytoin (a CYP 2C9 and CYP 2C19 substrate).

Drug interaction studies with other anticonvulsants have not been conducted. Routine monitoring should be performed when therapy with Vabra-TZ (Valdecoxib) is either initiated or discontinued in patients on anticonvulsant therapy.

Dextromethorphan

Dextromethorphan is primarily metabolized by CYP 2D6 and to a lesser extent by 3A4. Coadministration with Vabra-TZ (40 mg BID for 7 days) resulted in a significant increase in dextromethorphan plasma levels suggesting that, at these doses, Vabra-TZ (Valdecoxib) is a weak inhibitor of 2D6. Even so, dextromethorphan plasma concentrations in the presence of high doses of Vabra-TZ (Valdecoxib) were almost 5-fold lower than those seen in CYP 2D6 poor metabolizers suggesting that dose adjustment is not necessary.

Lithium

Vabra-TZ (Valdecoxib) 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing therapy with Vabra-TZ (Valdecoxib) in patients receiving lithium. Lithium carbonate (450 mg BID for 7 days) had no effect on Vabra-TZ (Valdecoxib) pharmacokinetics.

Warfarin

The effect of Vabra-TZ on the anticoagulant effect of warfarin (1–8 mg/day) was studied in healthy subjects by coadministration of Vabra-TZ (Valdecoxib) 40 mg BID for 7 days. Vabra-TZ (Valdecoxib) caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%, respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR) of warfarin. While mean INR values were only slightly increased with coadministration of Vabra-TZ (Valdecoxib), the day-to-day variability in individual INR values was increased. Anticoagulant therapy should be monitored, particularly during the first few weeks, after initiating therapy with Vabra-TZ (Valdecoxib) in patients receiving warfarin or similar agents.

Fluconazole and Ketoconazole

Ketoconazole and fluconazole are predominantly CYP 3A4 and 2C9 inhibitors, respectively. Concomitant single dose administration of Vabra-TZ (Valdecoxib) 20 mg with multiple doses of ketoconazole and fluconazole produced a significant increase in exposure of Vabra-TZ (Valdecoxib). Plasma exposure (AUC) to Vabra-TZ (Valdecoxib) was increased 62% when coadministered with fluconazole and 38% when coadministered with ketoconazole.

Glyburide

Glyburide is a CYP 2C9 substrate. Coadministration of Vabra-TZ (10 mg BID for 7 days) with glyburide (5 mg QD or 10 mg BID) did not affect the pharmacokinetics (exposure) of glyburide. Coadministration of Vabra-TZ (Valdecoxib) (40 mg BID (day 1) and 40 mg QD (days 2–7)) with glyburide (5 mg QD) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glyburide. Coadministration of Vabra-TZ (Valdecoxib) (40 mg BID (day 1) and 40 mg QD (days 2–7)) with glyburide (10 mg glyburide BID) resulted in 21% increase in glyburide AUC(0–12hr) and a 16% increase in glyburide Cmax leading to a 16%decrease in glucose AUC(0–24hr). Insulin parameters were not affected. Because changes in glucose concentrations with Vabra-TZ (Valdecoxib) coadministration were within the normal variability and individual glucose concentrations were above or near 70 mg/dL, dose adjustment for glyburide (5 mg QD and 10 mg BID) with Vabra-TZ (Valdecoxib) coadministration (up to 40 mg QD) is not indicated. Coadministration of glyburide with doses higher than 40 mg Vabra-TZ (Valdecoxib) (e.g., 40 mg BID) has not been studied.

Omeprazole

Omeprazole is a CYP 3A4 substrate and CYP 2C19 substrate and inhibitor. Vabra-TZ (Valdecoxib) steady state plasma concentrations (40 mg BID) were not affected significantly with multiple doses of omeprazole (40 mg QD). Coadministration with Vabra-TZ (Valdecoxib) increased exposure of omeprazole (AUC) by 46%. Drugs whose absorption is sensitive to pH may be negatively impacted by concomitant administration of omeprazole and Vabra-TZ (Valdecoxib). However, because higher doses (up to 360 mg QD) of omeprazole are tolerated in Zollinger-Ellison (ZE) patients, no dose adjustment for omeprazole is recommended at current doses. Coadministration of Vabra-TZ (Valdecoxib) with doses higher than 40 mg QD omeprazole has not been studied.

Oral Contraceptives

Vabra-TZ (40 mg BID) did not induce the metabolism of the combination oral contraceptive norethindrone/ethinyl estradiol (1 mg/0.035 mg combination, Ortho-Novum 1/35®). Coadministration of Vabra-TZ (Valdecoxib) and Ortho-Novum 1/35® increased the exposure of norethindrone and ethinyl estradiol by 20% and 34%, respectively. Although there is little risk for loss of contraceptive efficacy, the clinical significance of these increased exposures in terms of safety is not known. These increased exposures of norethindrone and ethinyl estradiol should be taken into consideration when selecting an oral contraceptive for women taking Vabra-TZ (Valdecoxib).

Diazepam

Diazepam (Valium®) is a CYP 3A4 and CYP 2C19 substrate. Plasma exposure of diazepam (10 mg BID) was increased by 28% following administration of Vabra-TZ (Valdecoxib) (40 mg BID) for 12 days, while plasma exposure of Vabra-TZ (Valdecoxib) (40 mg BID) was not substantially increased following administration of diazepam (10 mg BID) for 12 days. Although the magnitude of changes in diazepam plasma exposure when coadministered with Vabra-TZ (Valdecoxib) were not sufficient to warrant dosage adjustments, patients may experience enhanced sedative side effects caused by increased exposure of diazepam under this circumstance. Patients should be cautioned against engaging in hazardous activities requiring complete mental alertness such as operating machinery or driving a motor vehicle.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Vabra-TZ was not carcinogenic in rats given oral doses up to 7.5 mg/kg/day for males and 1.5 mg/kg/day for females (equivalent to approximately 2- to 6-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)) or in mice given oral doses up to 25 mg/kg/day for males and 50 mg/kg/day for females (equivalent to approximately 0.6- to 2.4-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)) for two years.

Vabra-TZ (Valdecoxib) was not mutagenic in an Ames test or a mutation assay in Chinese hamster ovary (CHO) cells, nor was it clastogenic in a chromosome aberration assay in CHO cells or in an in vivo micronucleus test in rat bone marrow. Valdecoxib did not impair male rat fertility at oral doses up to 9.0 mg/kg/day (equivalent to approximately 3- to 6-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)). In female rats, a decrease in ovulation with increased pre- and post-implantation loss resulted in decreased live embryos/fetuses at doses ≥2 mg/kg/day (equivalent to approximately 2-fold human exposure at 20 mg QD as measured by the AUC(0–24hr) for Vabra-TZ (Valdecoxib)). The effects on female fertility were reversible. This effect is expected with inhibition of prostaglandin synthesis and is not the result of irreversible alteration of female reproductive function.

Pregnancy

Teratogenic Effects

Pregnancy Category C

The incidence of fetuses with skeletal anomalies such as semi-bipartite thoracic vertebra centra and fused sternebrae was slightly higher in rabbits at an oral dose of 40 mg/kg/day ) throughout organogenesis. Vabra-TZ (Valdecoxib) was not teratogenic in rabbits up to an oral dose of 10 mg/kg/day (equivalent to approximately 8-fold human exposures at 20 mg QD as measured by the AUC(0–24hr)).

Vabra-TZ (Valdecoxib) was not teratogenic in rats up to an oral dose of 10 mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)). There are no studies in pregnant women. However, Vabra-TZ (Valdecoxib) crosses the placenta in rats and rabbits. Vabra-TZ (Valdecoxib) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-teratogenic Effects

Vabra-TZ (Valdecoxib) caused increased pre- and post-implantation loss with reduced live fetuses at oral doses ≥10 mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)) in rats and an oral dose of 40 mg/kg/day (equivalent to approximately 72-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)) in rabbits throughout organogenesis. In addition, reduced neonatal survival and decreased neonatal body weight when rats were treated with Vabra-TZ (Valdecoxib) at oral doses ≥6 mg/kg/day (equivalent to approximately 7-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)) throughout organogenesis and lactation period. No studies have been conducted to evaluate the effect of Vabra-TZ (Valdecoxib) on the closure of the ductus arteriosus in humans. Therefore, as with other drugs known to inhibit prostaglandin synthesis, use of Vabra-TZ (Valdecoxib) during the third trimester of pregnancy should be avoided.

Labor and Delivery

Vabra-TZ produced no evidence of delayed labor or parturition at oral doses up to 10 mg/kg/day in rats (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC(0–24hr)). The effects of Vabra-TZ (Valdecoxib) on labor and delivery in pregnant women are unknown.

Nursing Mothers

Vabra-TZ (Valdecoxib) and its active metabolite are excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for adverse reactions in nursing infants from Vabra-TZ (Valdecoxib), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the importance of nursing to the infant.

Pediatric Use

Safety and effectiveness of Vabra-TZ in pediatric patients below the age of 18 years have not been evaluated.

Geriatric Use

Of the patients who received Vabra-TZ (Valdecoxib) in arthritis clinical trials of three months duration, or greater, approximately 2100 were 65 years of age or older, including 570 patients who were 75 years or older. No overall differences in effectiveness were observed between these patients and younger patients.

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ADVERSE REACTIONS

Of the patients treated with Vabra-TZ Tablets in controlled arthritis trials, 2665 were patients with OA, and 2684 were patients with RA. More than 4000 patients have received a chronic total daily dose of Vabra-TZ (Valdecoxib) 10 mg or more. More than 2800 patients have received Vabra-TZ (Valdecoxib) 10 mg/day, or more, for at least 6 months and 988 of these have received Vabra-TZ (Valdecoxib) for at least 1 year.

Osteoarthritis and Rheumatoid Arthritis

Table 4 lists all adverse events, regardless of causality, that occurred in ≥2.0% of patients receiving Vabra-TZ (Valdecoxib) 10 and 20 mg/day in studies of three months or longer from 7 controlled studies conducted in patients with OA or RA that included a placebo and/or a positive control group.

(Total Daily Dose)
Vabra-TZ (Valdecoxib) DiclofenacIbuprofenNaproxen
Adverse Event

Number Treated

Placebo

973

10 mg

1214

20 mg

1358

150 mg

711

2400 mg

207

1000 mg

766

Autonomic Nervous System Disorders
Hypertension0.61.62.12.52.41.7
Body as a Whole
Back pain1.61.62.72.81.41.0
Edema peripheral0.72.43.03.22.92.1
Influenza-like symptoms2.22.02.23.12.92.0
Injury accidental2.84.03.73.93.93.0
Central and Peripheral Nervous System Disorders
Dizziness2.12.62.74.23.42.7
Headache7.14.88.56.64.35.5
Gastrointestinal System Disorders
Abdominal fullness2.02.11.93.02.92.5
Abdominal pain6.37.08.217.08.210.1
Diarrhea4.25.46.010.83.94.7
Dyspepsia6.37.98.713.415.012.9
Flatulence4.12.93.53.17.75.4
Nausea5.97.06.38.47.78.7
Musculoskeletal System Disorders
Myalgia1.62.01.92.42.41.4
Respiratory System Disorders
Sinusitis2.22.61.81.13.43.4
Upper respiratory tract infection6.06.75.76.34.36.4
Skin and Appendages Disorders
Rash1.01.42.11.50.51.4

In these placebo- and active-controlled clinical trials, the discontinuation rate due to adverse events was 7.5% for arthritis patients receiving Vabra-TZ (Valdecoxib) 10 mg daily, 7.9% for arthritis patients receiving Vabra-TZ (Valdecoxib) 20 mg daily and 6.0%for patients receiving placebo.

In the seven controlled OA and RA studies, the following adverse events occurred in 0.1–1.9% of patients treated with Vabra-TZ (Valdecoxib) 10–20 mg daily, regardless of causality.Application site disorders: Cellulitis, dermatitis contactCardiovascular: Aggravated hypertension, aneurysm, angina pectoris, arrhythmia, cardiomyopathy, congestive heart failure, coronary artery disorder, heart murmur, hypotensionCentral, peripheral nervous system: Cerebrovascular disorder, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, paresthesia, tremor, twitching, vertigoEndocrine: GoiterFemale reproductive: Amenorrhea, dysmenorrhea, leukorrhea, mastitis, menstrual disorder, menorrhagia, menstrual bloating, vaginal hemorrhageGastrointestinal: Abnormal stools, constipation, diverticulosis, dry mouth, duodenal ulcer, duodenitis, eructation, esophagitis, fecal incontinence, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux, hematemesis, hematochezia, hemorrhoids, hemorrhoids bleeding, hiatal hernia, melena, stomatitis, stool frequency increased, tenesmus, tooth disorder, vomitingGeneral: Allergy aggravated, allergic reaction, asthenia, chest pain, chills, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, halitosis, malaise, pain, periorbital swelling, peripheral painHearing and vestibular: Ear abnormality, earache, tinnitusHeart rate and rhythm: Bradycardia, palpitation, tachycardiaHemic: AnemiaLiver and biliary system: Hepatic function abnormal, hepatitis, ALT increased, AST increasedMale reproductive: Impotence, prostatic disorderMetabolic and nutritional: Alkaline phosphatase increased, BUN increased, CPK increased, creatinine increased, diabetes mellitus, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipemia, hyperuricemia, hypocalcemia, hypokalemia, LDH increased, thirst increased, weight decrease, weight increase, xerophthalmiaMusculoskeletal: Arthralgia, fracture accidental, neck stiffness, osteoporosis, synovitis, tendonitisNeoplasm: Breast neoplasm, lipoma, malignant ovarian cystPlatelets (bleeding or clotting): Ecchymosis, epistaxis, hematoma NOS, thrombocytopeniaPsychiatric: Anorexia, anxiety, appetite increased, confusion, depression, depression aggravated, insomnia, nervousness, morbid dreaming, somnolenceResistance mechanism disorders: Herpes simplex, herpes zoster, infection fungal, infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis mediaRespiratory: Abnormal breath sounds, bronchitis, bronchospasm, coughing, dyspnea, emphysema, laryngitis, pneumonia, pharyngitis, pleurisy, rhinitisSkin and appendages: Acne, alopecia, dermatitis, dermatitis fungal, eczema, photosensitivity allergic reaction, pruritus, rash erythematous, rash maculopapular, rash psoriaform, skin dry, skin hypertrophy, skin ulceration, sweating increased, urticariaSpecial senses: Taste perversionUrinary system: Albuminuria, cystitis, dysuria, hematuria, micturition frequency increased, pyuria, urinary incontinence, urinary tract infectionVascular: Claudication intermittent, hemangioma acquired, varicose veinVision: Blurred vision, cataract, conjunctival hemorrhage, conjunctivitis, eye pain, keratitis, vision abnormalWhite cell and RES disorders: Eosinophilia, leukopenia, leukocytosis, lymphadenopathy, lymphangitis, lymphopeniaOther serious adverse events that were reported rarely (estimated <0.1%) in clinical trials, regardless of causality, in patients taking Vabra-TZ (Valdecoxib):Autonomic nervous system disorders: Hypertensive encephalopathy, vasospasmCardiovascular: Abnormal ECG, aortic stenosis, atrial fibrillation, carotid stenosis, coronary thrombosis, heart block, heart valve disorders, mitral insufficiency, myocardial infarction, myocardial ischemia, pericarditis, syncope, thrombophlebitis, unstable angina, ventricular fibrillationCentral, peripheral nervous system: ConvulsionsEndocrine: HyperparathyroidismFemale reproductive: Cervical dysplasiaGastrointestinal: Appendicitis, colitis with bleeding, dysphagia, esophageal perforation, gastrointestinal bleeding, ileus, intestinal obstruction, peritonitisHemic: Lymphoma-like disorder, pancytopeniaLiver and biliary system: Cholelithiasis Metabolic: DehydrationMusculoskeletal: Pathological fracture, osteomyelitisNeoplasm: Benign brain neoplasm, bladder carcinoma, carcinoma, gastric carcinoma, prostate carcinoma, pulmonary carcinomaPlatelets (bleeding or clotting): Embolism, pulmonary embolism, thrombosisPsychiatric: Manic reaction, psychosisRenal: Acute renal failureResistance mechanism disorders: SepsisRespiratory: Apnea, pleural effusion, pulmonary edema, pulmonary fibrosis, pulmonary infarction, pulmonary hemorrhage, respiratory insufficiencySkin: Basal cell carcinoma, malignant melanomaUrinary system: Pyelonephritis, renal calculusVision: Retinal detachment

Postmarketing Experience

The following reactions have been identified during postmarketing use of Vabra-TZ (Valdecoxib). These reactions have been chosen for inclusion either due to their seriousness, reporting frequency, possible causal relationship to Vabra-TZ (Valdecoxib), or a combination of these factors. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General: Hypersensitivity reactions (including anaphylactic reactions and angioedema)Gastrointestinal: PancreatitisSkin and appendages: Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

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OVERDOSAGE

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.

Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Hemodialysis removed only about 2% of administered Vabra-TZ (Valdecoxib) from the systemic circulation of 8 patients with end-stage renal disease and, based on its degree of plasma protein binding (>98%), dialysis is unlikely to be useful in overdose. Forced diuresis, alkalinization of urine, or hemoperfusion also may not be useful due to high protein binding.

DOSAGE AND ADMINISTRATION

Osteoarthritis and Adult Rheumatoid Arthritis

The recommended dose of Vabra-TZ Tablets for the relief of the signs and symptoms of arthritis is 10 mg once daily.

Primary Dysmenorrhea

The recommended dose of Vabra-TZ (Valdecoxib) Tablets for treatment of primary dysmenorrhea is 20 mg twice daily, as needed.

HOW SUPPLIED

Vabra-TZ (Valdecoxib) Tablets 10 mg are white, film-coated, and capsule-shaped, debossed "10" on one side with a four pointed star shape on the other, supplied as:

NDC Number Size
0025-1975-31Bottle of 100
0025-1975-51Bottle of 500
0025-1975-34Carton of 100 unit dose

Vabra-TZ (Valdecoxib) Tablets 20 mg are white, film-coated, and capsule-shaped, debossed "20" on one side with a four pointed star shape on the other, supplied as:

NDC NumberSize
0025-1980-31Bottle of 100
0025-1980-51Bottle of 500
0025-1980-34Carton of 100 unit dose

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).

Rx only

LAB-0266-7.0

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Vabra-TZ pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Vabra-TZ available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Vabra-TZ destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Vabra-TZ Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Vabra-TZ pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."BEXTRA (VALDECOXIB) TABLET, FILM COATED [G.D. SEARLE LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."VALDECOXIB: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "tizanidine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Vabra-TZ?

Depending on the reaction of the Vabra-TZ after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Vabra-TZ not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Vabra-TZ addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Vabra-TZ, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Vabra-TZ consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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