Indatab may be available in the countries listed below.
Ingredient matches for Indatab
Indapamide
Indapamide is reported as an ingredient of Indatab in the following countries:
- Vietnam
International Drug Name Search
Wednesday, 26 September 2012
Monday, 24 September 2012
Glyburide Tablets
Glyburide Tablets (micronized), USP contain smaller particle size. Glyburide is an oral blood-glucose-lowering drug of the sulfonylurea class. Glyburide is a white, crystalline compound. Each tablet, for oral administration, contains 1.5 mg, 3 mg, or 6 mg of glyburide. Inactive ingredients: microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate. In addition, the 3 mg, and 6 mg strengths contain FD&C Blue No. 1 and FD&C Blue No. 2. The chemical name for glyburide is 1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea. The molecular formula is C23H28ClN3O5S, and the molecular weight is 494.01. The structural formula is represented below:
Glyburide Tablets - Clinical Pharmacology
Actions
Glyburide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which glyburide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. The combination of glyburide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms.
Some patients who are initially responsive to oral hypoglycemic drugs, including glyburide, may become unresponsive or poorly responsive over time. Alternatively, glyburide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs.
In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Disulfiram-like reactions have very rarely been reported in patients treated with glyburide.
Pharmacokinetics
Single dose studies with Glyburide Tablets (micronized) in normal subjects demonstrate significant absorption of glyburide within one hour, peak drug levels at about two to three hours, and low but detectable levels at twenty-four hours.
Bioavailability studies have demonstrated that Glyburide Tablets (micronized) 3 mg provide serum glyburide concentrations that are not bioequivalent to those from nonmicronized Glyburide Tablets 5 mg. Therefore, the patient should be retitrated.
In a single-dose bioavailability study (see Figure A) in which subjects received Glyburide Tablets (micronized) 3 mg and nonmicronized Glyburide Tablets 5 mg with breakfast, the peak of the mean serum glyburide concentration-time curve was 97.2 ng/mL for Glyburide Tablets (micronized) 3 mg and 87.5 ng/mL for nonmicronized Glyburide Tablets 5 mg. The mean of the individual maximum serum concentration values of glyburide (Cmax) from Glyburide Tablets (micronized) 3 mg was 106 ng/mL and that from nonmicronized Glyburide Tablets 5 mg was 104 ng/mL. The mean glyburide area under the serum concentration-time curve (AUC) for this study was 568 ng x hr/mL for Glyburide Tablets (micronized) 3 mg and 746 ng x hr/mL for nonmicronized Glyburide Tablets 5 mg.
Mean serum levels of glyburide, as reflected by areas under the serum concentration-time curve, increase in proportion to corresponding increases in dose. Multiple dose studies with glyburide in diabetic patients demonstrate drug level concentration-time curves similar to single dose studies, indicating no buildup of drug in tissue depots.
In a steady-state study in diabetic patients receiving Glyburide Tablets (micronized) 6 mg once daily or Glyburide Tablets (micronized) 3 mg twice daily, no difference was seen between the two dosage regimens in average 24 hour glyburide concentrations following two weeks of dosing. The once-daily and twice-daily regimens provided equivalent glucose control as measured by fasting plasma glucose levels, 4 hour postprandial glucose AUC values, and 24 hour glucose AUC values. Insulin AUC response over the 24 hour period was not different for the two regimens. There were differences in insulin response between the regimens for the breakfast and supper 4 hour postprandial periods, but these did not translate into differences in glucose control.
The serum concentration of glyburide in normal subjects decreased with a half-life of about four hours.
In single dose studies in fasting normal subjects who were administered nonmicronized Glyburide Tablets in doses ranging from 1.25 mg to 5 mg, the degree and duration of blood glucose lowering is proportional to the dose administered and to the area under the drug level concentration-time curve. The blood glucose lowering effect persists for 24 hours following single morning doses in nonfasting diabetic patients. Under conditions of repeated administration in diabetic patients, however, there is no reliable correlation between blood drug levels and fasting blood glucose levels. A one year study of diabetic patients treated with glyburide showed no reliable correlation between administered dose and serum drug level.
The major metabolite of glyburide is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites probably contribute no significant hypoglycemic action in humans since they are only weakly active (1/400th and 1/40th as active, respectively, as glyburide) in rabbits.
Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.
Sulfonylurea drugs are extensively bound to serum proteins. Displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. In vitro, the protein binding exhibited by glyburide is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. Acidic drugs such as phenylbutazone, warfarin, and salicylates displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding glyburide. It has not been shown that this difference in protein binding will result in fewer drug-drug interactions with glyburide in clinical use.
Indications and Usage for Glyburide Tablets
Glyburide Tablets (micronized) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Contraindications
Glyburide Tablets (micronized) are contraindicated in patients with:
- Known hypersensitivity or allergy to the drug.
- Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
- Type I diabetes mellitus.
SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes, 19 (Suppl. 2):747-830, 1970).
UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2 1/2 times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glyburide (micronized) and of alternative modes of therapy.
Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
Precautions
Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glyburide (micronized) or any other antidiabetic drug.
Bioavailability studies have demonstrated that Glyburide Tablets (micronized) 3 mg provide serum glyburide concentrations that are not bioequivalent to those from nonmicronized Glyburide Tablets 5 mg. Therefore, patients should be retitrated when transferred from nonmicronized glyburide or other oral hypoglycemic agents.
General
Hypoglycemia
All sulfonylureas are capable of producing severe hypoglycemia. Proper patient selection and dosage and instructions are important to avoid hypoglycemic episodes. Renal or hepatic insufficiency may cause elevated drug levels of glyburide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose lowering drug is used. The risk of hypoglycemia may be increased with combination therapy.
Loss of Control of Blood Glucose
When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection or surgery, a loss of control may occur. At such times it may be necessary to discontinue glyburide (micronized) and administer insulin.
The effectiveness of any hypoglycemic drug, including glyburide (micronized), in lowering blood glucose to a desired level decreases in many patients over a period of time which may be due to progression of the severity of diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when glyburide (micronized) is first given. Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.
Hemolytic Anemia
Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because glyburide (micronized) belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered. In postmarketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
Information for Patients
Patients should be informed of the potential risks and advantages of glyburide (micronized) and of alternative modes of therapy. They also should be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure also should be explained.
Physician Counseling Information for Patients
In initiating treatment for type 2 diabetes, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The importance of regular physical activity should also be stressed, and cardiovascular risk factors should be identified and corrective measures taken where possible. Use of glyburide (micronized) or other antidiabetic medications must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitution or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of glyburide (micronized) or other antidiabetic medications. Maintenance or discontinuation of glyburide (micronized) or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.
Laboratory Tests
Therapeutic response to Glyburide Tablets (micronized) should be monitored by frequent urine glucose tests and periodic blood glucose tests. Measurement of glycosylated hemoglobin levels may be helpful in some patients.
Drug Interactions
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including non-steroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving glyburide, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glyburide, the patient should be observed closely for loss of control.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glyburide, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving glyburide, the patient should be observed closely for hypoglycemia.
A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism of action for this interaction is not known.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known.
Metformin
In a single-dose interaction study in NIDDM subjects, decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain. Coadministration of glyburide and metformin did not result in any changes in either metformin pharmacokinetics or pharmacodynamics.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies in rats at doses up to 300 mg/kg/day for 18 months showed no carcinogenic effects. Glyburide is nonmutagenic when studied in the Salmonella microsome test (Ames test) and in the DNA damage/alkaline elution assay.
No drug-related effects were noted in any of the criteria evaluated in the two-year oncogenicity study of glyburide in mice.
Pregnancy
Teratogenic Effects
Pregnancy category B
Reproduction studies have been performed in rats and rabbits at doses up to 500 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to glyburide. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose as close to normal as possible.
Nonteratogenic Effects
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glyburide (micronized) is used during pregnancy, it should be discontinued at least two weeks before the expected delivery date.
Nursing Mothers
Although it is not known whether glyburide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, 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. If the drug is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see DOSAGE AND ADMINISTRATION).
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function.
Adverse Reactions
Hypoglycemia
See PRECAUTIONS and OVERDOSAGE sections.
Gastrointestinal Reactions
Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; Glyburide Tablets (micronized) should be discontinued if this occurs.
Liver function abnormalities, including isolated transaminase elevations, have been reported.
Gastrointestinal disturbances, e.g., nausea, epigastric fullness, and heartburn are the most common reactions, having occurred in 1.8% of treated patients during clinical trials. They tend to be dose related and may disappear when dosage is reduced.
Dermatologic Reactions
Allergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions occurred in 1.5% of treated patients during clinical trials. These may be transient and may disappear despite continued use of glyburide. If skin reactions persist, the drug should be discontinued.
Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
Hematologic Reactions
Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see PRECAUTIONS), aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic Reactions
Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas; however, hepatic porphyria has not been reported with glyburide and disulfiram-like reactions have been reported very rarely.
Cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.
Other Reactions
Changes in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. These are thought to be related to fluctuation in glucose levels.
In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.
Overdosage
Overdosage of sulfonylureas, including glyburide, can produce hypoglycemia. Mild hypoglycemic symptoms, without loss of consciousness or neurological findings, should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate which will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery.
Glyburide Tablets Dosage and Administration
Patients should be retitrated when transferred from nonmicronized Glyburide Tablets or other oral hypoglycemic agents.
There is no fixed dosage regimen for the management of diabetes mellitus with Glyburide Tablets (micronized), USP or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient’s blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of adequate blood glucose lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient’s response to therapy.
Short-term administration of Glyburide Tablets (micronized), USP may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
Usual Starting Dose
The suggested starting dose of Glyburide Tablets (micronized), USP is 1.5 to 3 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 0.75 mg daily (see PRECAUTIONS for patients at increased risk). Failure to follow an appropriate dosage regimen may precipitate hypoglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy.
Transfer From Other Hypoglycemic Therapy; Patients Receiving Other Oral Antidiabetic Therapy
Patients should be retitrated when transferred from nonmicronized Glyburide Tablets or other oral hypoglycemic agents. The initial daily dose should be 1.5 to 3 mg. When transferring patients from oral hypoglycemic agents other than chlorpropamide to Glyburide Tablets (micronized), USP, no transition period and no initial or priming dose are necessary. When transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia.
Patients Receiving Insulin
Some Type II diabetic patients being treated with insulin may respond satisfactorily to Glyburide Tablets (micronized), USP. If the insulin dose is less than 20 units daily, substitution of Glyburide Tablets (micronized), USP 1.5 to 3 mg as a single daily dose may be tried. If the insulin dose is between 20 and 40 units daily, the patient may be placed directly on Glyburide Tablets (micronized), USP 3 mg daily as a single dose. If the insulin dose is more than 40 units daily, a transition period is required for conversion to Glyburide Tablets (micronized), USP. In these patients, insulin dosage is decreased by 50% and Glyburide Tablets (micronized), USP 3 mg daily is started. Please refer to Titration to Maintenance Dose for further explanation.
Titration to Maintenance Dose
The usual maintenance dose is in the range of 0.75 to 12 mg daily, which may be given as a single dose or in divided doses (see Dosage Interval). Dosage increases should be made in increments of no more than 1.5 mg at weekly intervals based upon the patient’s blood glucose response.
No exact dosage relationship exists between Glyburide Tablets (micronized), USP and the other oral hypoglycemic agents, including nonmicronized Glyburide Tablets. Although patients may be transferred from the maximum dose of other sulfonylureas, the maximum starting dose of 3 mg of Glyburide Tablets (micronized), USP should be observed. A maintenance dose of 3 mg of Glyburide Tablets (micronized), USP provides approximately the same degree of blood glucose control as 250 to 375 mg chlorpropamide, 250 to 375 mg tolazamide, 5 mg of glyburide (nonmicronized tablets), 500 to 750 mg acetohexamide, or 1000 to 1500 mg tolbutamide.
When transferring patients receiving more than 40 units of insulin daily, they may be started on a daily dose of Glyburide Tablets (micronized), USP 3 mg concomitantly with a 50% reduction in insulin dose. Progressive withdrawal of insulin and increase of Glyburide Tablets (micronized), USP in increments of 0.75 to 1.5 mg every 2 to 10 days is then carried out. During this conversion period when both insulin and Glyburide Tablets (micronized), USP are being used, hypoglycemia may rarely occur. During insulin withdrawal, patients should test their urine for glucose and acetone at least three times daily and report results to their physician. The appearance of persistent acetonuria with glycosuria indicates that the patient is a Type I diabetic who requires insulin therapy.
Concomitant Glyburide and Metformin Therapy
Glyburide Tablets (micronized), USP should be added gradually to the dosing regimen of patients who have not responded to the maximum dose of metformin monotherapy after four weeks (see Usual Starting Dose and Titration to Maintenance Dose). Refer to metformin package insert.
With concomitant glyburide and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the optimal dose of each drug needed to achieve this goal. With concomitant glyburide and metformin therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken (see PRECAUTIONS).
Maximum Dose
Daily doses of more than 12 mg are not recommended.
Dosage Interval
Once-a-day therapy is usually satisfactory. Some patients, particularly those receiving more than 6 mg daily, may have a more satisfactory response with twice-a-day dosage.
Specific Patient Populations
Glyburide Tablets (micronized), USP are not recommended for use in pregnancy or for use in pediatric patients.
In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS).
How is Glyburide Tablets Supplied
Glyburide Tablets (micronized), USP are supplied as follows:
Glyburide Tablets (micronized), USP 1.5 mg are white, oval-shaped, flat face, beveled-edge, compressed tablets, debossed with 1.5 | 034 on one side and stylized N on the reverse. They are supplied as follows:
NDC 0093-8034-01 bottles of 100
Glyburide Tablets (micronized), USP 3 mg are pale-blue colored, oval-shaped, flat face, beveled-edge, compressed tablets, debossed with 3 | 035 on one side and stylized N on the reverse. They are supplied as follows:
NDC 0093-8035-01 bottles of 100
NDC 0093-8035-05 bottles of 500
NDC 0093-8035-50 bottles of 5000
Glyburide Tablets (micronized), USP 6 mg are dark-blue colored, oval-shaped, flat face, beveled-edge, compressed tablets, debossed with 6 | 036 on one side and stylized N on the reverse. They are supplied as follows:
NDC 0093-8036-01 bottles of 100
The glyburide tablet (micronized), USP can be easily divided in half for a more flexible dosing regimen. Press gently on the score and the tablet will split in even halves.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with safety closure. Keep container tightly closed.
Manufactured In Canada By:
TEVA CANADA LIMITED
Toronto, Canada M1B 2K9
Manufactured For:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. I 10/2011
PRINCIPAL DISPLAY PANEL
Glyburide Tablets (Micronized) USP 1.5 mg 100s Label Text
NDC 0093-8034-01
Glyburide Tablets
(micronized), USP
1.5 mg
Rx only
100 TABLETS
TEVA
PRINCIPAL DISPLAY PANEL
Glyburide Tablets (Micronized) USP 3 mg 100s Label Text
NDC 0093-8035-01
Glyburide Tablets
(micronized), USP
3 mg
Rx only
100 TABLETS
TEVA
PRINCIPAL DISPLAY PANEL
Glyburide Tablets (Micronized) USP 6 mg 100s Label Text
NDC 0093-8036-01
Glyburide Tablets
(micronized), USP
6 mg
Rx only
100 TABLETS
TEVA
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| Labeler - Teva Pharmaceuticals USA Inc (118234421) |
Sunday, 23 September 2012
Caraco Pharmaceutical Laboratories
AddressCaraco Pharmaceutical Laboratories, 1150 Elijah McCoy Drive, Detroit, MI 48202 Contact DetailsPhone: (800) 818-4555Website: http://www.caraco.com/ Careers: http://www.caraco.com/aspx/CareerHome.aspx |
Saturday, 22 September 2012
Stalevo 50 / 12.5 / 200mg
Stalevo 50 mg/12.5 mg/200 mg film-coated tablets
Levodopa/carbidopa/entacapone
Read all of this leaflet carefully before you start taking this medicine.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it to others. It may harm them, even if their symptoms are the same as yours.
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
In this leaflet:
1. What Stalevo is and what it is used for
2. Before you take Stalevo
3. How to take Stalevo
4. Possible side effects
5 How to store Stalevo
6. Further information
What Stalevo Is And What It Is Used For
Stalevo contains three active substances (levodopa, carbidopa and entacapone) in one film-coated tablet. Stalevo is used for the treatment of Parkinson’s disease.
Parkinson’s disease is caused by low levels of a substance called dopamine in the brain. Levodopa increases the amount of dopamine and hence reduces the symptoms of Parkinson’s disease. Carbidopa and entacapone improve the antiparkinson effects of levodopa.
Before You Take Stalevo
Do not take Stalevo if you
- are allergic (hypersensitive) to levodopa, carbidopa or entacapone, or any of the other ingredients of Stalevo
- have narrow-angle glaucoma (an eye disorder)
- have a tumour of the adrenal gland
- are taking certain medicines for treating depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO-inhibitors)
- have ever had neuroleptic malignant syndrome (NMS – this is a rare reaction to medicines used to treat severe mental disorders)
- have ever had non-traumatic rhabdomyolysis (a rare muscle disorder)
- have a severe liver disease.
Take special care with Stalevo
Consult your doctor if you have or have ever had:
- a heart attack or any other diseases of the heart including cardiac arrythmias, or of the blood vessels
- asthma or any other disease of the lungs
- a liver problem, because your dose may need to be adjusted
- kidney or hormone-related diseases
- tomach ulcers or convulsions
- if you experience prolonged diarrhoea consult your doctor as it may be a sign of inflammation of the colon
- any form of severe mental disorder like psychosis
- chronic wide-angle glaucoma, because your dose may need to be adjusted and the pressure in your eyes may need to be monitored.
Consult your doctor if you are currently taking:
- antipsychotics (medicines used to treat psychosis)
- a medicine which may cause low blood pressure when rising from a chair or bed. You should be aware that Stalevo may make these reactions worse.
Consult your doctor if during the treatment with Stalevo you:
- notice that your muscles get very rigid or jerk violently, or if you get tremors, agitation, confusion,fever, rapid pulse, or wide fluctuations in your blood pressure. If any of this happens, contact your doctor immediately
- feel depressed, have suicidal thoughts, or notice unusual changes in your behaviour
- find yourself suddenly falling asleep, or if you feel very drowsy. If this happens, you should not drive or use any tools or machines (see also section 'Driving and using machines')
- notice that uncontrolled movements begin or get worse after you started to take Stalevo. If this happens, your doctor may need to change the dose of your antiparkinson medicine
- experience diarrhoea: monitoring of your weight is recommended in order to avoid potentially excessive weight loss
- experience progressive anorexia, asthenia (weakness, exhaustion) and weight decrease within a relatively short period of time. If this happens, a general medical evaluation including liver function should be considered
- experience excessive gambling or excessive sexual activity
- feel the need to stop using Stalevo, see section 'If you stop taking Stalevo'.
Your doctor may take some regular laboratory tests during a long term treatment with Stalevo.
If you must undergo surgery, please tell your doctor that you are using Stalevo.
Stalevo is not recommended to be used for treatment of extrapyramidal symptoms (e.g. involuntary movements, shaking, muscle rigidity and muscle contractions) caused by other medicines.
Children
Experience with Stalevo in patients under 18 years is limited. Therefore, the use of Stalevo in children is not recommended.
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal medicines.
Do not take Stalevo if you are taking certain medicines for treating depression (combinations of selective MAO-A and MAO-B inhibitors, or non-selective MAO inhibitors).
Stalevo may increase the effects and side effects of certain medicines. These include:
- medicines used to treat depression such as moclobemide, amitryptiline, desipramine, maprotiline, venlafaxine and paroxetine
- rimiterole and isoprenaline, used to treat respiratory diseases
- adrenaline, used for severe allergic reactions
- noradrenaline, dopamine and dobutamine, used to treat heart diseases and low blood pressure
alpha-methyldopa, used to treat high blood pressure - apomorphine, which is used to treat Parkinson’s disease.
The effects of Stalevo may be weakened by certain medicines. These include:
- dopamine antagonists used to treat mental disorders, nausea and vomiting
- phenytoin, used to prevent convulsions
- papaverine used to relax the muscles.
Stalevo may make it harder for you to digest iron. Therefore, do not take Stalevo and iron supplements at the same time. After taking one of them, wait at least 2 to 3 hours before taking the other.
Taking Stalevo with food and drink
Stalevo may be taken with or without food. For some patients, Stalevo may not be well absorbed if it is taken with, or shortly after eating protein-rich food (such as meats, fish, dairy products, seeds and nuts). Consult your doctor if you think this applies to you.
Pregnancy and breast-feeding
If you are pregnant or think you may be pregnant, consult your doctor before taking Stalevo.
You should not breast-feed during treatment with Stalevo.
Driving and using machines
Stalevo may lower your blood pressure, which may make you feel light-headed or dizzy. Therefore, be particularly careful when you drive or when you use any tools or machines.
If you feel very drowsy, or if you sometimes find yourself suddenly falling asleep, wait until you feel fully awake again before driving or doing anything else that requires you to be alert. Otherwise, you may put yourself and others at risk of serious injury or death.
Important information about some of the ingredients of Stalevo
Stalevo contains sucrose (1.2 mg/tablet). If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.
How To Take Stalevo
Always take Stalevo exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
For adults and elderly:
- Your doctor will tell you exactly how many tablets of Stalevo to take each day.
- The tablets are not intended to be split or broken into smaller pieces.
- You should take only one tablet each time.
- Depending on how you respond to treatment, your doctor may suggest a higher or lower dose.
- If you are taking Stalevo 50 mg/12.5 mg/200 mg, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg or 150 mg/37.5 mg/200 mg tablets, do not take more than 10 tablets per day.
Talk to your doctor or pharmacist if you think the effect of Stalevo is too strong or too weak, or if you experience possible side effects
If you take more Stalevo than you should
If you have accidentally taken more Stalevo tablets than you should, talk to your doctor or pharmacist immediately.
If you forget to take Stalevo
Do not take a double dose to make up for a forgotten tablet.
If it is more than 1 hour until your next dose:
Take one tablet as soon as you remember, and the next tablet at the normal time.
If it is less than 1 hour until your next dose:
Take a tablet as soon as you remember, wait 1 hour, then take another tablet. After that carry on as normal.
Always leave at least an hour between Stalevo tablets, to avoid possible side effects.
If you stop taking Stalevo
Do not stop taking Stalevo unless your doctor tells you to. In such a case your doctor may need to adjust your other antiparkinson medicines, especially levodopa, to give sufficient control of your symptoms. If you suddenly stop taking Stalevo and other antiparkinsonian medicines it may result in unwanted side effects.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Stalevo 50/12.5/200mg Side Effects
Like all medicines, Stalevo can cause side effects, although not everybody gets them. If you experience any of these side effects, talk to your doctor as soon as possible. Many of the side effects can be relieved by adjusting the dose.
The frequencies are defined as:
Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)
Not known (frequency cannot be estimated from the available data).
Very common
- uncontrolled movements (dyskinesias), worsening of Parkinson’s symptoms
- feeling sick (nausea)
- harmless reddish-brown discoloration of urine
Common
- light-headedness or fainting due to low blood pressure
- dizziness, drowsiness, tingling or numbness
- vomiting, abdominal pain, dry mouth, constipation, diarrhoea
- inability to sleep, hallucinations, confusion, nightmares, feeling agitated, tiredness
- mental changes – including paranoid and psychotic symptoms, depression (possibly with thoughts of suicide) and problems with memory or thinking
- heart or artery disease events (e.g. chest pain), irregular heart rate or rhythm
- more frequent falling
- shortness of breath
- increased sweating, itching and rashes
- muscle cramps
- vision disturbances
Uncommon
- heart attack
- loss of appetite, weight loss or gain, bleeding in the gut, duodenal ulcers
- high blood pressure
- changes in the blood cell count (which may result in symptoms such as tiredness, fainting, infections, bleeding)
- inflammation of the veins in the legs
- convulsions
The following side effects have also been reported:
- colitis (inflammation of the colon)
- hepatitis (inflammation of the liver)
- skin, hair, beard and nail discolorations
If you during the treatment with Stalevo experience the following symptoms, contact your doctor immediately:
- Your muscles get very rigid or jerk violently, you get tremors, agitation, confusion, fever, rapid pulse, or wide fluctuations in your blood pressure. These can be symptoms of neuroleptic malignant syndrome (NMS, a rare severe reaction to medicines used to treat disorders of the central nervous system) or rhabdomyolysis (a rare severe muscle disorder).
- Allergic reaction, the signs may include hives (nettle rash), itching, rash, swelling of your face, lips, tongue or throat. This may cause difficulties in breathing or swallowing.
Behavioural changes such as urge to gamble (pathological gambling) or increased sexual desire and urges (increased libido and hypersexuality) have been reported in patients receiving dopamine replacement therapy including Stalevo.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
How To Store Stalevo
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the bottle and the carton after EXP. The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Further Information
What Stalevo contains
- The active substances of Stalevo are levodopa, carbidopa and entacapone.
- Each Stalevo 50 mg/12.5 mg/200 mg tablet contains 50 mg of levodopa, 12.5 mg of carbidopa and 200 mg of entacapone.
- The other ingredients in the tablet core are croscarmellose sodium, magnesium stearate, maize starch, mannitol (E421) and povidone (E1201)
- The ingredients in the film-coating are glycerol (85 per cent) (E422), hypromellose, magnesium stearate, polysorbate 80, red iron oxide (E172), sucrose, titanium dioxide (E171), and yellow iron oxide (E172).
What Stalevo looks like and contents of the pack
Stalevo 50 mg/12.5 mg/200 mg: brownish or greyish red, round, convex unscored film-coated tablets marked with ‘LCE 50’ on one side.
Stalevo comes in six different pack sizes (10, 30, 100, 130, 175 or 250 tablets). Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.
United Kingdom
Orion Pharma (UK) Ltd.
Tel:+44 1635 520 300
This leaflet was last approved on 2 June 2010
Detailed information on this medicine is available on the European Medicine’s Agency (EMA) web site: http://www.ema.europa.eu
Wednesday, 19 September 2012
Cetirizine hydrochloride 10 mg film-coated tablets
1. Name Of The Medicinal Product
Cetirizine hydrochloride 10 mg film-coated tablets
2. Qualitative And Quantitative Composition
Each film-coated tablet contains 10 mg cetirizine hydrochloride.
Excipient: 155.2 mg lactose monohydrate/ film-coated tablet
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Film-coated tablet.
White to off-white, film-coated, off-rectangular tablets, debossed with 'X' on one side with '20' on the other side. Score line between '2' and '0'.
The tablet can be divided into equal halves.
4. Clinical Particulars
4.1 Therapeutic Indications
In adults and paediatric patients 6 years and above:
• Cetirizine is indicated for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.
• Cetirizine is indicated for the relief of symptoms of chronic idiopathic urticaria.
4.2 Posology And Method Of Administration
Oral use.
Children aged from 6 to 12 years: 5mg twice daily (a half tablet twice daily).
Adults and adolescents over 12 years of age: 10mg once daily (1 tablet).
The tablets need to be swallowed with a glass of liquid.
Elderly subjects: data do not suggest that the dose needs to be reduced in elderly subjects provided that the renal function is normal.
Patients with moderate to severe renal impairment: there are no data to document the efficacy/safety ratio in patients with renal impairment. Since cetirizine is mainly excreted via renal route (see section 5.2), in cases no alternative treatment can be used, the dosing intervals must be individualized according to renal function. Refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in ml/min is needed. The CLcr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following formula:
Dosing adjustments for adult patients with impaired renal function
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In paediatric patients suffering from renal impairment, the dose will have to be adjusted on an individual basis taking into account the renal clearance of the patient, his age and his body weight.
Patients with hepatic impairment: no dose adjustment is needed in patients with solely hepatic impairment.
Patients with hepatic impairment and renal impairment: dose adjustment is recommended (see Patients with moderate to severe renal impairment above).
4.3 Contraindications
• Hypersensitivity to the active substance, to any of the excipients, to hydroxyzine or to any piperazine derivatives.
• Patients with severe renal impairment at less than 10 ml/min creatinine clearance.
4.4 Special Warnings And Precautions For Use
At therapeutic doses, no clinically significant interactions have been demonstrated with alcohol (for a blood alcohol level of 0.5 g/L). Nevertheless, precaution is recommended if alcohol is taken concomitantly.
Caution in epileptic patients and patients at risk of convulsions is recommended.
The use of the film-coated tablet formulation is not recommended in children aged less than 6 years since this formulation does not allow for appropriate dose adaptation.
Allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
Cetirizine 10 mg film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Due to the pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Actually, neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400 mg/day).
The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.
4.6 Pregnancy And Lactation
Pregnancy
For cetirizine very rare clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.
Lactation
Cetirizine is excreted in human milk at concentrations representing 0.25 to 0.90 those measured in plasma, depending on sampling time after administration. Therefore, caution should be exercised when prescribing cetirizine to lactating women.
4.7 Effects On Ability To Drive And Use Machines
Objective measurements of driving ability, sleep latency and assembly line performance have not demonstrated any clinically relevant effects at the recommended dose of 10mg.
Patients intending to drive, engaging in potentially hazardous activities or operating machinery should not exceed the recommended dose and should take their response to the medicinal product into account. In these sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.
4.8 Undesirable Effects
Clinical studies have shown that cetirizine at the recommended dosage has minor undesirable effects on the CNS, including somnolence, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulation has been reported.
Although cetirizine is a selective antagonist of peripheral H1-receptors and is relatively free of anticholinergic activity, isolated cases of micturition difficulty, eye accommodation disorders and dry mouth have been reported.
Instances of abnormal hepatic function with elevated hepatic enzymes accompanied by elevated bilirubin have been reported. Mostly this resolves upon discontinuation of the treatment with cetirizine hydrochloride.
Clinical trials:
Double blind controlled clinical or pharmacoclinical trials comparing cetirizine to placebo or other antihistamines at the recommended dosage (10mg daily for cetirizine), of which quantified safety data are available, included more than 3200 subjects exposed to cetirizine.
From this pooling, the following adverse events were reported for cetirizine 10mg in the placebo-controlled trials at rates of 1.0% or greater:
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Although statistically more common than under placebo, somnolence was mild to moderate in the majority of cases. Objective tests as demonstrated by other studies have demonstrated that usual daily activities are unaffected at the recommended daily dose in healthy young volunteers.
Adverse drug reactions at rates of 1% or greater in children aged from 6 months to 12 years, included in placebo-controlled clinical or pharmacological trials are:
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Post-marketing experience
In addition to the adverse effects reported during clinical studies and listed above, isolated cases of the following adverse drug reactions have been reported in post-marketing experience. For these less frequently reported undesirable effects, the estimated frequencies (uncommon:
Investigations:
Rare: weight increased
Cardiac disorders:
Rare: tachycardia
Blood and lymphatic disorders:
Very rare: thrombocytopenia
Nervous system disorders:
Uncommon: paraesthesia
Rare: convulsions, movement disorders
Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia
Not known: amnesia, memory impairment
Eye disorders:
Very rare: accommodation disorder, blurred vision, oculogyration
Gastrointestinal disorders:
Uncommon: diarrhoea
Renal and urinary disorders:
Very rare: dysuria, enuresis
Skin and subcutaneous tissue disorders:
Uncommon: pruritus, rash
Rare: urticaria.
Very rare: angioneurotic oedema, fixed drug eruption
General disorders and administration site conditions:
Uncommon: asthenia, malaise
Rare: oedema
Immune system disorders
Rare: hypersensitivity
Very rare: anaphylactic shock
Hepato-billiary disorders:
Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γ-GT and bilirubin)
Psychiatric disorders:
Uncommon: agitation
Rare: aggression, confusion, depression, hallucination, insomnia
Very rare: tics
4.9 Overdose
Symptoms:
Symptoms observed after an overdose of cetirizine are mainly associated with CNS effects or with effects that could suggest an anticholinergic effect.
Adverse events reported after an intake of at least 5 times the recommended daily dose are: confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia, tremor, and urinary retention.
Management:
There is no known specific antidote to cetirizine.
Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage should be considered following ingestion of a short occurrence.
Cetirizine is not effectively removed by dialysis.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Piperazine derivatives, ATC code: R06AE07
Cetirizine, a human metabolite of hydroxyzine, is a potent and selective antagonist of peripheral H1-receptors. In vitro receptors binding studies have shown no measurable affinity for other than H1-receptors.
In addition to its anti-H1 effect, cetirizine was shown to display anti-allergic activities: at a dose of 10mg once or twice daily, it inhibits the late phase recruitment of eosinophils, in the skin and conjunctiva of atopic subjects submitted to allergen challenge.
Studies in healthy volunteers show that cetirizine, at doses of 5 and 10mg strongly inhibits the wheal and flare reactions induced by very high concentrations of histamine into the skin, but the correlation with efficacy is not established.
In a 35-day study in children aged 5 to 12, no tolerance to the antihistaminic effect (suppression of wheal and flare) of cetirizine was found. When a treatment with cetirizine is stopped after repeated administration, the skin recovers its normal reactivity to histamine within 3 days.
In a six-week, placebo-controlled study of 186 patients with allergic rhinitis and concomitant mild to moderate asthma, cetirizine 10mg once daily improved rhinitis symptoms and did not alter pulmonary function. This study supports the safety of administering cetirizine to allergic patients with mild to moderate asthma.
In a placebo-controlled study, cetirizine given at the high daily dose of 60mg for seven days did not cause statistically significant prolongation of QT interval.
At the recommended dosage, cetirizine has demonstrated that it improves the quality of life of patients with perennial and seasonal allergic rhinitis.
5.2 Pharmacokinetic Properties
The steady-state peak plasma concentrations is approximately 300 ng/ml and is achieved within 1.0 ± 0.5 h. No accumulation is observed for cetirizine following daily doses of 10 mg for 10 days. The distribution of pharmacokinetic parameters such as peak plasma concentration (Cmax) and area under curve (AUC), is unimodal in human volunteers.
The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased. The extent of bioavailability is similar when cetirizine is given as solutions, capsules or tablets.
The apparent volume of distribution is 0.50 l/kg. Plasma protein binding of cetirizine is 93 ± 0.3%. Cetirizine does not modify the protein binding of warfarin.
Cetirizine does not undergo extensive first pass metabolism. About two third of the dose are excreted unchanged in urine. The terminal half-life is approximately 10 hours.
Cetirizine exhibits linear kinetics over the range of 5 to 60mg.
Special populations
Elderly: Following a single 10mg oral dose, half-life increased by about 50% and clearance decreased by 40% in 16 elderly subjects compared to the normal subjects. The decrease in cetirizine clearance in these elderly volunteers appeared to be related to their decreased renal function.
Children, infants and toddlers: The half-life of cetirizine was about 6 hours in children of 6-12 years and 5 hours in children 2-6 years. In infants and toddlers aged 6 to 24 months, it is reduced to 3.1 hours.
Renally impaired patients: The pharmacokinetics of the drug were similar in patients with mild impairment (creatinine clearance higher than 40ml/min) and healthy volunteers. Patients with moderate renal impairment had a 3-fold increase in half-life and a 70% decrease in clearance compared to healthy volunteers.
Patients on haemodialysis (creatinine clearance less than 7 ml/min) given a single oral 10mg dose of cetirizine had a 3-fold increase in half-life and a 70% decrease in clearance compared to normals. Cetirizine was poorly cleared by haemodialysis. Dosing adjustment is necessary in patients with moderate or severe renal impairment (see section 4.2).
Hepatically impaired patients: Patients with chronic liver disease (hepatocellular, cholestatic, and biliary cirrhosis) given 10 or 20mg of cetirizine as a single dose had a 50% increase in half-life along with a 40% decrease in clearance compared to healthy subjects.
Dosing adjustment is only necessary in hepatically impaired patients if concomitant renal impairment is present.
5.3 Preclinical Safety Data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential or toxicity to reproduction.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Tablet core:
Lactose monohydrate
Crospovidone
Starch, pregelatinised (maize)
Magnesium stearate
Film-coat:
Hypromellose
Titanium dioxide
Macrogol 400
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
Blister pack: 1 year
HDPE bottle pack: 18 months
6.4 Special Precautions For Storage
Store below 25°C.
6.5 Nature And Contents Of Container
PVC-PVDC Aluminium blisters: 1,2, 7, 10, 14, 15, 20, 21, 30, 50, 60, 90, 98 and 100 film-coated tablets.
HDPE bottle: 250 film-coated tablets.
Not all pack sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
No special requirements.
7. Marketing Authorisation Holder
Aurobindo Pharma (Malta) Limited
46/2, South street, Valletta, VLT 11, Malta
8. Marketing Authorisation Number(S)
PL 32256/0036
9. Date Of First Authorisation/Renewal Of The Authorisation
03/07/2009
10. Date Of Revision Of The Text
17/06/2011
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