TELMISARTAN AND HYDROCHLOROTHIAZIDE tablet

Land: Vereinigte Staaten

Sprache: Englisch

Quelle: NLM (National Library of Medicine)

Wirkstoff:

HYDROCHLOROTHIAZIDE (UNII: 0J48LPH2TH) (HYDROCHLOROTHIAZIDE - UNII:0J48LPH2TH), TELMISARTAN (UNII: U5SYW473RQ) (TELMISARTAN - UNII:U5SYW473RQ)

Verfügbar ab:

Lupin Pharmaceuticals, Inc.

INN (Internationale Bezeichnung):

HYDROCHLOROTHIAZIDE

Zusammensetzung:

HYDROCHLOROTHIAZIDE 25 mg

Verabreichungsweg:

ORAL

Verschreibungstyp:

PRESCRIPTION DRUG

Anwendungsgebiete:

Telmisartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with telmisartan and hydrochlorothiazide tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy [see Clinical Studies (14)]. Telmisartan and hydrochlorothiazide tablets are not indicated for initial therapy for the treatment of hypertension [see Dosage and Administration (2.1)]. Telmisartan and hydrochlorothiazide tablets may be used alone or in combination with other antihypertensive agents. Telmisartan and hydrochlorothiazide tablets are contraindicated: -   In patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.5)]. -   In patients with anuria. -   For co-administration with aliskiren in patients with diabetes [see Drug Interactions (7.4)]. Risk Summary Telmisartan and hydrochlorothiazide tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations) . Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin angiotensin system from other antihypertensive agents. Studies in rats and rabbits with telmisartan showed fetotoxicity only at maternally toxic doses (see  Data ). When pregnancy is detected, discontinue telmisartan and hydrochlorothiazide tablets as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions: Telmisartan Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. In patients taking telmisartan and hydrochlorothiazide tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue telmisartan and hydrochlorothiazide tablets, unless it is considered lifesaving for the mother. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to telmisartan and hydrochlorothiazide tablets for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function [see Use in Specific Populations (8.4) ]. Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults. Data Animal Data:   Telmisartan and hydrochlorothiazide tablets A developmental toxicity study was performed in rats with telmisartan/hydrochlorothiazide doses of 3.2/1.0, 15/4.7, 50/15.6, and 0/15.6 mg/kg/day. Although the two higher dose combinations appeared to be more toxic (significant decrease in body weight gain) to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. Telmisartan No teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses of up to 50 mg/kg/day and to pregnant rabbits at oral doses of up to 45 mg/kg/day. In rabbits, embryo lethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of 80 mg on a mg/m2 basis). In rats, maternally toxic (reduced body weight gain and food consumption) telmisartan doses of 15 mg/kg/day (approximately 1.9 times the MRHD on a mg/m2 basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. The no-observed effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are approximately 0.64 and 3.7 times, respectively, on a mg/m2 basis, the MRHD of telmisartan (80 mg/day). Hydrochlorothiazide Studies in which hydrochlorothiazide was administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the MRHD), provided no evidence of harm to the fetus. Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times that in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided. Risk Summary There is no information regarding the presence of telmisartan and hydrochlorothiazide tablets or telmisartan in human milk, the effects on the breastfed infant or the effects on milk production. Limited published studies report that hydrochlorothiazide is present in human milk. However, there is insufficient information to determine the effects of hydrochlorothiazide on the breastfed infant or the effects of hydrochlorothiazide on milk production. Telmisartan is present in the milk of lactating rats (see Data ). Because of the potential for serious adverse reactions in the breastfed infant including hypotension, hyperkalemia and renal impairment, advise a nursing woman not to breastfeed during treatment with telmisartan and hydrochlorothiazide tablets. Data Telmisartan was present in the milk of lactating rats at concentrations 1.5 to 2 times those found in plasma from 4 to 8 hours after administration. Safety and effectiveness of telmisartan and hydrochlorothiazide tablets in pediatric patients have not been established. Neonates with a history of in utero exposure to telmisartan and hydrochlorothiazide tablets If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. In the controlled clinical trials (n=1017), approximately 20% of patients treated with telmisartan/hydrochlorothiazide were 65 years of age or older, and 5% were 75 years of age or older. No overall differences in effectiveness and safety of telmisartan/hydrochlorothiazide were observed in these patients compared to younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy. Patients with biliary obstructive disorders or hepatic insufficiency should initiate treatment under close medical supervision using the 40 mg/12.5 mg combination. Telmisartan As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance and higher blood levels. Hydrochlorothiazide Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease. Safety and effectiveness of telmisartan and hydrochlorothiazide tablets in patients with severe renal impairment (CrCl ≤30 mL/min) have not been established. In patients with severe renal impairment, telmisartan and hydrochlorothiazide tablets are not recommended. No dose adjustment is required in patients with mild (CrCl 60 to 90 mL/min) or moderate (CrCl 30 to 60 mL/min) renal impairment.

Produktbesonderheiten:

Telmisartan and Hydrochlorothiazide Tablets USP are available in three strengths: 40 mg/12.5 mg: supplied as oval shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is red coloured and telmisartan layer is white to off-white in colour but may have red specks; debossed with 'M31' on one side and 'LU' on other side. Bottle of 30's: NDC 68180-193-06 Bottle of 90's: NDC 68180-193-09 Unit Dose Blisters of 3 X 10s NDC 68180-193-13 80 mg/12.5 mg: supplied as capsule shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is red coloured and telmisartan layer is white to off-white in colour but may have red specks; debossed with 'M32' on one side and 'LU' on other side. Bottle of 30's: NDC 68180-194-06 Bottle of 90's: NDC 68180-194-09 Unit Dose Blisters of 3 X 10s NDC 68180-194-13 80 mg/25 mg: supplied as capsule shaped, biconvex, bilayer, uncoated tablets; where hydrochlorothiazide layer is yellow coloured and telmisartan layer is white to off-white in colour but may have yellow specks; debossed with 'M33' on one side and 'LU' on other side. Bottle of 30's: NDC 68180-195-06 Bottle of 90's: NDC 68180-195-09 Unit Dose Blisters of 3 X 10s NDC 68180-195-13 Storage Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].

Berechtigungsstatus:

Abbreviated New Drug Application

Fachinformation

TELMISARTAN AND HYDROCHLOROTHIAZIDE- TELMISARTAN AND
HYDROCHLOROTHIAZIDE TABLET
LUPIN PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TELMISARTAN AND
HYDROCHLOROTHIAZIDE TABLETS SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION
FOR TELMISARTAN AND HYDROCHLOROTHIAZIDE TABLETS.
TELMISARTAN AND HYDROCHLOROTHIAZIDE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2000
WARNING: FETAL TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_.
WHEN PREGNANCY IS DETECTED, DISCONTINUE TELMISARTAN AND
HYDROCHLOROTHIAZIDE
TABLETS AS SOON AS POSSIBLE. (5.1, 8.1)
DRUGS THAT ACT DIRECTLY ON THE RENIN-ANGIOTENSIN SYSTEM CAN CAUSE
INJURY AND DEATH
TO THE DEVELOPING FETUS. (5.1, 8.1)
INDICATIONS AND USAGE
Telmisartan and hydrochlorothiazide tablets are combination of an
angiotensin II receptor blocker (ARB)
and a thiazide diuretic indicated for the treatment of hypertension,
alone or with other antihypertensive
agents, to lower blood pressure. Lowering blood pressure reduces the
risk of fatal and nonfatal
cardiovascular events, primarily strokes and myocardial infarctions
(1)
Telmisartan and hydrochlorothiazide tablets are not indicated for
initial therapy (1)
DOSAGE AND ADMINISTRATION
Usual starting dose is 80 mg/12.5 mg once daily (2.1)
Titrate up to 160 mg/25 mg as needed (2.1)
Initiate patients with biliary obstructive disorders or hepatic
insufficiency at 40 mg/12.5 mg (2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 40 mg/12.5 mg, 80 mg/12.5 mg, 80 mg/25 mg (3)
CONTRAINDICATIONS
Hypersensitivity to telmisartan or any component (4)
Anuria (4)
Co-Administration with aliskiren in patients with diabetes (4)
WARNINGS AND PRECAUTIONS
Avoid fetal or neonatal exposure (5.1)
Correct volume or salt depletion before initiating therapy. Observe
for signs and symptoms of
hypotension (5.2)
Monitor renal function and potassium in susceptible patients (5.3)
Observe for clinical signs of fluid or electrolyte imbalance (5.4)
Hypersensitivity Rea