isk 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. thalitone can be used alone or in combination with other antihypertensive agents. 1.2 edema chlorthalidone is indicated in adults as adjunctive therapy in edema associated with heart failure, cirrhosis of the liver, and renal disease, including nephrotic syndrome.

sk of developing acute renal failure on thalitone. monitor renal function periodically. consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on thalitone [see drug interactions (7)]. 5.3 electrolyte abnormalities thalitone can cause hypokalemia, hyponatremia, hypochloremic alkalosis, and hypomagnesemia. hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. monitor serum electrolytes periodically. if hypokalemia is accompanied by clinical signs (e.g., muscular weakness, paresis, or ecg alterations), thalitone should be discontinued. correction of hypokalemia and any coexisting hypomagnesemia is recommended prior to the initiation of thiazides. 5.4 metabolic disturbances chlorthalidone may alter glucose tolerance. chlorthalidone may raise serum levels of cholesterol and triglycerides. chlorthalidone may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients. chlorthalidone decreases urinary calcium excretion and may cause elevations of serum calcium. monitor calcium levels in patients with hypercalcemia receiving thalitone.

ommended initial dosage is 50 to 100 mg daily or 100 mg on alternate days. depending on response, dosage can be decreased or increased up to a maximum of 200 mg daily.

�™s syndrome (toxic epidermal necrolysis). cardiovascular reaction: orthostatic hypotension. other adverse reactions: muscle spasm, weakness, restlessness, impotence, xanthopsia. the most frequently expected adverse drug reactions among patients receiving thalitone are hypotension, dizziness, renal dysfunction, and electrolyte abnormalities (6). to report suspected adverse reactions, contact casper pharma llc at 1-844-5-casper (1-844-522-7737) or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

kground 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 risks 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 stillbirth. fetal/neonatal adverse reactions thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. thiazides, like other diuretics, can cause placental hypoperfusion. use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, hypoglycemia, and electrolyte abnormalities. thiazides do not prevent or alter the course of eph (edema, proteinuria, hypertension) gestosis (pre-eclampsia) and should not be used as first-line therapy to treat hypertension in pregnant women. data animal data reproduction studies have been performed in the rat and the rabbit and have revealed no evidence of harm to the fetus due to chlorthalidone.the available data do not allow the calculation of comparisons between the exposure of chlorthalidone observed in animal studies to the systemic exposure that would be expected in humans. 8.2 lactation risk summary chlorthalidone is present in human milk. there is no information regarding the effects of chlorthalidone on the breastfed infant or the effects on milk production. because of the potential for chlorthalidone accumulation which may lead to serious adverse reactions in the breastfed infant (such as jaundice, thrombocytopenia, hyperglycemia, electrolyte abnormalities), advise patients that breastfeeding is not recommended during treatment with chlorthalidone. 8.4 pediatric use safety and effectiveness in children have not been established. 8.5 geriatric use clinical studies of thalitone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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 disease or other drug therapy. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

sease-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 stillbirth. fetal/neonatal adverse reactions thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. thiazides, like other diuretics, can cause placental hypoperfusion. use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, hypoglycemia, and electrolyte abnormalities. thiazides do not prevent or alter the course of eph (edema, proteinuria, hypertension) gestosis (pre-eclampsia) and should not be used as first-line therapy to treat hypertension in pregnant women. data animal data reproduction studies have been performed in the rat and the rabbit and have revealed no evidence of harm to the fetus due to chlorthalidone.the available data do not allow the calculation of comparisons between the exposure of chlorthalidone observed in animal studies to the systemic exposure that would be expected in humans.

hlorthalidone produces dose-related reductions in serum potassium levels, elevations in serum uric acid and blood glucose, and it can lead to decreased sodium and chloride levels. 12.3 pharmacokinetics absorption thalitone (chlorthalidone usp) has been formulated with pvp (povidone polyvinylpyrrolidone), a bioavailability enhancer that provides 104% to 116% bioavailability relative to an oral solution of chlorthalidone [see clinical studies (14)]. thalitone cannot be substituted with other formulations of chlorthalidone. distribution in the blood, approximately 75% of the drug is bound to plasma proteins over a concentration range of 0.2 to 7.7 ug/ml. elimination the mean plasma half-life of chlorthalidone is about 40 to 60 hours. it is eliminated primarily as unchanged drug in the urine.

mg) pairwise comparison 2 through 12 weeks 4 through 12 weeks mean change (95% ci) significance level mean change (95% ci) significance level standing sbp, mm hg thalitone 15 mg vs. placebo −11.77 vs. −1.89 (−13.02, −6.74) <0.001 −12.43 vs. −2.02 (−13.87, −6.95) <0.001 thalitone 15 mg vs. standard chlorthalidone 25 mg −11.77 vs. −11.73 (−3.18, 3.1) 0.98 −12.43 vs. −11.70 (−4.19, 2.73) 0.68 standing dbp, mm hg thalitone 15 mg vs. placebo −5.95 vs. −3.28 (−4.5, −0.84) <0.01 −6.64 vs. −3.42 (−5.29, −1.15) <0.01 thalitone 15 mg vs. standard chlorthalidone 25 mg − 5.95 vs. −6.79 (−0.99, 2.67) 0.37 −6.64 vs. −7.06 (−1.65, 2.49) 0.69 supine sbp, mm hg thalitone 15 mg vs. placebo −8.42 vs. −2.63 (−8.87, −2.71) <0.001 −8.91 vs. −2.85 (-9.46, -2.66) <0.001 thalitone 15 mg vs. standard chlorthalidone 25 mg −8.42 vs. −10.31 (−1.19, 4.97) 0.23 −8.91 vs. −10.61 (−1.70, 5.10) 0.33 supine dbp, mm hg thalitone 15 mg vs. placebo −6.44 vs. −4.16 (−4.46, −0.11) 0.04 −6.72 vs. −4.28 (−4.85, −0.03) 0.05 thalitone 15 mg vs. standard chlorthalidone 25 mg −6.44 vs. −6.82 (−1.80, 2.56) 0.73 −6.72 vs. −7.05 (−2.08, 2.74) 0.79 sbp: systolic blood pressure, dbp: diastolic blood pressure, ci: confidence interval table 2. mean changes in laboratory parameters (thalitone 15 mg vs. standard chlorthalidone 25 mg) parameter thalitone 15 mg standard chlorthalidone 25 mg placebo potassium (mmol/l) baseline n/a n/a n/a 4 weeks −0.35 (0.08)* −0.53 (0.05)* 0.10 (0.05) 12 weeks −0.31 (0.07)* −0.55 (0.06)* 0.12 (0.06) cholesterol (mg/dl) baseline n/a n/a n/a 4 weeks 5.51 (3.70)* 5.14 (3.29)* −7.18 (3.30) 12 weeks 9.34 (3.03) 8.11 (3.86) 0.26 (4.53) glucose (mg/dl) baseline n/a n/a n/a 4 weeks 1.83 (2.55) 6.56 (2.36) 1.52 (2.17) 12 weeks −0.84 (2.58) + 11.02 (2.71)* −1.83 (2.29) uric acid (mg/dl) baseline n/a n/a n/a 4 weeks 0.66 (0.16)* 1.04 (0.14)* −0.34 (0.15) 12 weeks 0.71 (0.13)* 1.10 (0.14)* −0.19 (0.15) *p<0.05 vs. placebo +p<0.05 vs. standard chlorthalidone 25 mg n/a: not applicable

india. revised: 12/2019