Telmisartan and Hydrochlorothiazide

1 INDICATIONS AND USAGE 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 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 The usual starting dose of telmisartan is 40 mg once a day; blood pressure response is dose related over the range of 20 to 80 mg. Patients with depletion of intravascular volume should have the condition corrected or telmisartan tablets should be initiated under close medical supervision (see WARNINGS, Hypotension in Volume Depleted Patients ). Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision (see PRECAUTIONS ). Hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg once daily. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. The side effects (see WARNINGS ) of telmisartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of telmisartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects. Telmisartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents. Telmisartan and hydrochlorothiazide tablets may be administered with or without food. Replacement Therapy The combination may be substituted for the titrated components. Dose Titration by Clinical Effect Telmisartan and hydrochlorothiazide tablets are available as tablets containing either telmisartan 40 mg and hydrochlorothiazide 12.5 mg, or telmisartan 80 mg and hydrochlorothiazide 12.5 mg or 25 mg. A patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg (see above) may be switched to telmisartan and hydrochlorothiazide tablets, telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily, and finally titrated up to 160/25 mg, if necessary. A patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg or telmisartan 80 mg/hydrochlorothiazide 25 mg tablets once daily. The clinical response to telmisartan and hydrochlorothiazide tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 2 to 4 weeks of therapy, the dose may be titrated up to 160/25 mg, if necessary. Those patients controlled by 25 mg hydrochlorothiazide but who experience hypokalemia with this regimen, may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg tablets once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. Patients with Renal Impairment The usual regimens of therapy with telmisartan and hydrochlorothiazide tablets may be followed as long as the patient’s creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so telmisartan and hydrochlorothiazide tablets are not recommended. Patients with Hepatic Impairment Telmisartan and hydrochlorothiazide tablets are not recommended for patients with severe hepatic impairment. Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision using the 40/12.5 mg combination (see PRECAUTIONS ).

3 DOSAGE FORMS AND STRENGTHS • 40 mg/12.5 mg: Biconvex, two-layered, capsule shaped uncoated tablets wherein, the hydrochlorothiazide layer is white to off-white debossed with “423” and the telmisartan layer is mottled orange to reddish brown without debossing. Hydrochlorothiazide layer may contain reddish brown specks. • 80 mg/12.5 mg: Biconvex, two-layered, capsule shaped uncoated tablets wherein, the hydrochlorothiazide layer is white to off-white debossed with “424” and the telmisartan layer is mottled orange to reddish brown without debossing. Hydrochlorothiazide layer may contain reddish brown specks. • 80 mg/25 mg: Biconvex, two-layered, capsule shaped uncoated tablets wherein, the hydrochlorothiazide layer is light yellow debossed with “425” and the telmisartan layer is mottled orange to reddish brown without debossing. Hydrochlorothiazide layer may contain reddish brown specks. Tablets: 40 mg/12.5 mg, 80 mg/12.5 mg, 80 mg/25 mg ( 3 )

CONTRAINDICATIONS Telmisartan and hydrochlorothiazide tablets, USP are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, hydrochlorothiazide, or any other component of this product (see ADVERSE REACTIONS ). Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not co-administer aliskiren with telmisartan and hydrochlorothiazide tablets in patients with diabetes (see PRECAUTIONS , Drug Interactions ).

ADVERSE REACTIONS Telmisartan and hydrochlorothiazide tablets has been evaluated for safety in over 1700 patients, including 716 treated for over six months and 420 for over one year. In clinical trials with telmisartan and hydrochlorothiazide tablets, no unexpected adverse events have been observed. Adverse experiences have been limited to those that have been previously reported with telmisartan and/or hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo. Most adverse experiences were mild in intensity and transient in nature and did not require discontinuation of therapy. Adverse events occurring at an incidence of 2% or more in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo, irrespective of their causal association, are presented in Table 1. TABLE 1 Adverse Events Occurring ≥2% of Telmisartan/Hydrochlorothiazide (HCTZ) Patients* Telm/HCTZ (N=414) (%) Placebo (N=74) (%) Telm (N=209) (%) HCTZ (N=121) (%) Body as a whole Fatigue 3 1 3 3 Influenza-like symptoms 2 1 2 3 Central/peripheral nervous system Dizziness 5 1 4 6 Gastrointestinal system Diarrhea 3 0 5 2 Nausea 2 0 1 2 Respiratory system disorder Sinusitis 4 3 3 6 Upper respiratory tract infection 8 7 7 10 * includes all doses of telmisartan (20 to 160 mg), hydrochlorothiazide (6.25 to 25 mg), and combinations thereof The following adverse events were reported at a rate less than 2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo: back pain, dyspepsia, vomiting, tachycardia, hypokalemia, bronchitis, pharyngitis, rash, hypotension postural, abdominal pain. Finally, the following adverse events were reported at a rate of 2% or greater in patients treated with telmisartan/hydrochlorothiazide, but were as, or more common in the placebo group: pain, headache, cough, urinary tract infection. Adverse events occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients. In controlled trials (n=1017), 0.3% of patients treated with telmisartan and hydrochlorothiazide tablets 40/12.5 mg, 80/12.5 mg or 80/25 mg discontinued due to orthostatic hypotension, and the incidence of dizziness was 4%, 7%, and 1% respectively. Telmisartan Other adverse experiences that have been reported with telmisartan, without regard to causality, are listed below: Autonomic Nervous System : impotence, increased sweating, flushing Body as a Whole : allergy, fever, leg pain, malaise, chest pain Cardiovascular : palpitation, dependent edema, angina pectoris, leg edema, abnormal ECG, hypertension, peripheral edema CNS : insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoaesthesia Gastrointestinal : flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders Metabolic : gout, hypercholesterolemia, diabetes mellitus Musculoskeletal : arthritis, arthralgia, leg cramps, myalgia Psychiatric : anxiety, depression, nervousness Resistance Mechanism : infection, fungal infection, abscess, otitis media Respiratory : asthma, rhinitis, dyspnea, epistaxis Skin : dermatitis, eczema, pruritus Urinary : micturition frequency, cystitis Vascular : cerebrovascular disorder Special Senses : abnormal vision, conjunctivitis, tinnitus, earache A single case of angioedema was reported (among a total of 3781 patients treated with telmisartan). Hydrochlorothiazide Other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below: Body as a whole : weakness Digestive : pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation Hematologic : aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia Hypersensitivity …

Drug Interactions Telmisartan Aliskiren: Do not co-administer aliskiren with telmisartan and hydrochlorothiazide tablets in patients with diabetes. Avoid use of aliskiren with telmisartan and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/min). Digoxin : When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. It is, therefore, recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing telmisartan to avoid possible over- or under-digitalization. Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Cases have also been reported with angiotensin II receptor antagonists including telmisartan. Because lithium should not be used with diuretics, the use of lithium with telmisartan and hydrochlorothiazide is not recommended. Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) : In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors. Ramipril and Ramiprilat: Co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state C max and AUC of ramipril 2.3 and 2.1 fold, respectively, and C max and AUC of ramiprilat 2.4 and 1.5 fold, respectively. In contrast, C max and AUC of telmisartan decrease by 31% and 16%, respectively. When co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. Warfarin : Telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a change in International Normalized Ratio (INR). Other Drugs : Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19. Hydrochlorothiazide When administered concurrently, the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics : Potentiation of orthostatic hypotension may occur. Antidiabetic drugs (oral agents and insulin) : Dosage adjustment of the antidiabetic drug may be required. Other antihypertensive drugs : Additive effect or potentiation. Cholestyramine and colestipol resins : Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. Corticosteroids, ACTH : Intensified electrolyte depletion, particularly hypokalemia. Pressor amines (e.g., norepinephrine) : Possible decreased respons …

8 USE IN SPECIFIC POPULATIONS Lactation: Do not breastfeed during treatment with telmisartan and hydrochlorothiazide (8.2) Severe Hepatic Impairment: Use not recommended (8.6) Severe Renal Impairment: Use not recommended (8.7) 8.1 Pregnancy Risk Summary Telmisartan and hydrochlorothiazide 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 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 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, 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 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 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 pr …

12.1 Mechanism of Action Telmisartan and Hydrochlorothiazide Tablets Telmisartan and hydrochlorothiazide tablets are a combination of two drugs with antihypertensive properties: a thiazide diuretic, hydrochlorothiazide, and an angiotensin II receptor blocker (ARB), telmisartan. Telmisartan Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3,000-fold) for the AT1 receptor than for the AT 2 receptor. Telmisartan does not inhibit ACE (kininase II) nor does it bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure. Hydrochlorothiazide Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium salt and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an ARB tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is not fully understood.

11 DESCRIPTION Telmisartan and Hydrochlorothiazide Tablets, USP are a combination of telmisartan, USP an orally active angiotensin II antagonist acting on the AT 1 receptor subtype, and hydrochlorothiazide, USP a thiazide diuretic. Telmisartan, USP a non-peptide molecule, is chemically described as 4’-[[4-methyl- 6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl] methyl]-2-biphenylcarboxylic acid. Its empirical formula is C 33 H 30 N 4 O 2 , its molecular weight is 514.62, and its structural formula is: Telmisartan, USP is a white or slightly yellowish crystalline powder. It is practically insoluble in water, slightly soluble in methanol, sparingly soluble in methylene chloride and it dissolves in 1M sodium hydroxide. Hydrochlorothiazide, USP is a white or practically white, practically odorless, crystalline powder with a molecular weight of 297.74. It is very slightly soluble in water, and freely soluble in sodium hydroxide solution, in n -butylamine and in dimethylformamide, sparingly soluble in methanol; insoluble in ether, in chloroform and dilute mineral acids. Hydrochlorothiazide, USP is chemically described as 6-chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C 7 H 8 ClN 3 O 4 S 2 , and its structural formula is: Telmisartan and Hydrochlorothiazide Tablets, USP are formulated for oral administration in three combinations of 40 mg/12.5 mg, 80 mg/12.5 mg, and 80 mg/25 mg telmisartan, USP and hydrochlorothiazide, USP respectively. The tablets contain the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, mannitol, meglumine, povidone K-25, sodium hydroxide, sodium stearyl fumarate and talc. As coloring agents, the 40 mg/12.5 mg, 80 mg/12.5 mg, and 80 mg/25 mg tablets contain ferric oxide red, the 80 mg/25 mg tablets also contain ferric oxide yellow. Telmisartan and Hydrochlorothiazide Tablets, USP are hygroscopic and require protection from moisture. FDA approved dissolution test specifications differ from USP. structure1 structure2

10 OVERDOSAGE Telmisartan Limited data are available with regard to overdosage of telmisartan in humans. The most likely manifestations of overdosage with telmisartan are hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemofiltration and is not dialyzable. Hydrochlorothiazide The most common signs and symptoms observed in patients with a hydrochlorothiazide overdose are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD 50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

HOW SUPPLIED Telmisartan and hydrochlorothiazide tablets are available in three strengths as 40 mg/12.5 mg, 80 mg/12.5 mg and 80 mg/25 mg. 40 mg/12.5 mg: Oblong shaped, biconvex, bilayered, uncoated tablets with one white to off white color layer and one pink color mottled layer debossed with ‘L199’.White to off white color layer may contains pink color specks. NDC 46708-209-30 bottle of 30 units NDC 46708-209-91 bottle of 1000 units NDC 46708-209-10 100 Tablets (i.e.; 10 blister cards of 10 tablets each) 80 mg/12.5 mg: Oblong shaped, biconvex, bilayered, uncoated tablets with one white to off white color layer and one pink color mottled layer debossed with ‘L200’. White to off white color layer may contains pink color specks. NDC 46708-210-30 bottle of 30 units NDC 46708-210-91 bottle of 1000 units NDC 46708-210-10 100 Tablets (i.e.; 10 blister cards of 10 tablets each) 80 mg/25 mg: Oblong shaped, biconvex, bilayered, uncoated tablets with one white to off white color layer and one yellow color mottled layer debossed with ‘L201’. White to off white color layer may contains yellow color specks. NDC 46708-211-30 bottle of 30 units NDC 46708-211-91 bottle of 1000 units NDC 46708-211-10 100 Tablets (i.e.; 10 blister cards of 10 tablets each) Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Tablets should not be removed from blisters until immediately before administration. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Manufactured by: Alembic Pharmaceuticals Limited (Formulation Division), Village Panelav, P. O. Tajpura, Near Baska, Taluka-Halol, Panchmahal, Gujarat, India. Revised: 03/2014