Complete SPL Sections#
SPL UNCLASSIFIED SECTION
SPL UNCLASSIFIED SECTION
novaplus TM + Rx Only
DESCRIPTION
DESCRIPTION SECTION
Chlorothiazide Sodium for Injection, USP is a diuretic and antihypertensive. It is 6-chloro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide monosodium salt and its molecular weight is 317.71. Its empirical formula is C 7 H 5 ClN 3 NaO 4 S 2 and its structural formula is: Chlorothiazide Sodium for Injection, USP is a sterile lyophilized white powder and is supplied in a vial containing: Chlorothiazide sodium equivalent to chlorothiazide 500 mg, and the inactive ingredient mannitol 250 mg with sodium hydroxide to adjust pH. Chlorothiazide is a diuretic and antihypertensive. It is 6-chloro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C 7 H 6 ClN 3 O 4 S 2 and its structural formula is: It is a white, or practically white, crystalline powder with a molecular weight of 295.72, which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide. It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
The mechanism of the antihypertensive effect of thiazides is unknown. Chlorothiazide does not usually affect normal blood pressure. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours. Following intravenous use of chlorothiazide sodium, onset of the diuretic action occurs in 15 minutes and the maximal action in 30 minutes.
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Chlorothiazide Sodium for Injection, USP is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Chlorothiazide Sodium for Injection, USP has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
Anuria. Hypersensitivity to any component of this product or to other sulfonamide-derived drugs.
WARNINGS
WARNINGS SECTION
Intravenous use in infants and children has been limited and is not generally recommended. Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function. Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Thiazides may add to or potentiate the action of other antihypertensive drugs. Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported. Lithium generally should not be given with diuretics (see PRECAUTIONS, Drug Interactions ).
PRECAUTIONS
PRECAUTIONS SECTION
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity. Body as a Whole : Weakness. Cardiovascular : Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs). Digestive : Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia. Hematologic : Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity : Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura. Metabolic : Electrolyte imbalance (see PRECAUTIONS ), hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal : Muscle spasm. Nervous System/Psychiatric : Vertigo, paresthesias, dizziness, headache, restlessness. Skin : Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia. Special Senses : Transient blurred vision, xanthopsia. Renal : Renal failure, renal dysfunction, interstitial nephritis, (see WARNINGS ); hematuria (following intravenous use). Urogenital : Impotence. Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn. To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
OVERDOSAGE
OVERDOSAGE SECTION
The most common signs and symptoms observed 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. In the event of overdosage, symptomatic and supportive measures should be employed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment. The degree to which chlorothiazide sodium is removed by hemodialysis has not been established. The intravenous LD 50 of chlorothiazide in the mouse is 1.1 g/kg.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
Chlorothiazide Sodium for Injection, USP should be reserved for patients unable to take oral medication or for emergency situations. Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response. Intravenous use in infants and children has been limited and is not generally recommended. When medication can be taken orally, therapy with chlorothiazide tablets or oral suspension may be substituted for intravenous therapy, using the same dosage schedule as for the parenteral route. Chlorothiazide Sodium for Injection, USP may be given slowly by direct intravenous injection or by intravenous infusion. Extravasation must be rigidly avoided. Do not give subcutaneously or intramuscularly. The usual adult dosage is 500 mg to 1 g once or twice a day. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on three to five days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.
HOW SUPPLIED
HOW SUPPLIED SECTION
Chlorothiazide Sodium for Injection, USP is supplied as follows: NDC Chlorothiazide Sodium for Injection, USP Package Factor 25021-305-66 500 mg Single-Dose Vial 1 vial per carton Chlorothiazide Sodium for Injection, USP is a dry, sterile lyophilized white powder usually in cake form, supplied in vials containing chlorothiazide sodium equivalent to 500 mg of chlorothiazide.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label NDC 25021-305-66 Rx ONLY Chlorothiazide Sodium for Injection, USP FOR THE PREPARATION OF INTRAVENOUS SOLUTIONS Single-Dose Vial For Intravenous Use 500 mg per vial
