Spironolactone and Hydrochlorothiazide (Page 4 of 4)

Spironolactone:

Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting.

Reproductive: Gynecomastia (see Precautions), inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast pain. Carcinoma of the breast has been reported in patients taking spironolactone but a cause and effect relationship has not been established.

Hematologic: Leukopenia (including agranulocytosis), thrombocytopenia.

Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis.

Metabolism: Hyperkalemia, electrolyte disturbances (see Warnings and Precautions).

Musculoskeletal: Leg cramps.

Nervous system/psychiatric: Lethargy, mental confusion, ataxia, dizziness, headache, drowsiness.

Liver/biliary: A very few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with spironolactone administration.

Renal: Renal dysfunction (including renal failure).

Skin: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, pruritus.

Post Marketing Experience

Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

OVERDOSAGE

The oral LD50 of spironolactone is greater than 1000 mg/kg in mice, rats, and rabbits. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Rarely, instances of hyponatremia, hyperkalemia (less commonly seen with spironolactone and hydrochlorothiazide tablets because the hydrochlorothiazide component tends to produce hypokalemia), or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage.

However, because spironolactone and hydrochlorothiazide tablets contain both spironolactone and hydrochlorothiazide, the toxic effects may be intensified, and signs of thiazide overdosage may be present. These include electrolyte imbalance such as hypokalemia and/or hyponatremia. The potassium-sparing action of spironolactone may predominate and hyperkalemia may occur, especially in patients with impaired renal function. BUN determinations have been reported to rise transiently with hydrochlorothiazide. There may be CNS depression with lethargy or even coma.

Treatment: Induce vomiting or evacuate the stomach by lavage. There is no specific antidote. Treatment is supportive to maintain hydration, electrolyte balance, and vital functions.

Patients who have renal impairment may develop spironolactone-induced hyperkalemia. In such cases, spironolactone and hydrochlorothiazide tablets should be discontinued immediately. With severe hyperkalemia, the clinical situation dictates the procedures to be employed. These include the intravenous administration of calcium chloride solution, sodium bicarbonate solution, and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. These are temporary measures to be repeated as required. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.

DOSAGE AND ADMINISTRATION

Optimal dosage should be established by individual titration of the components.

Edema in adults (congestive heart failure, hepatic cirrhosis, or nephrotic syndrome). The usual maintenance dose of spironolactone and hydrochlorothiazide tablets is 100 mg each of spironolactone and hydrochlorothiazide daily, administered in a single dose or in divided doses, but may range from 25 mg to 200 mg of each component daily depending on the response to the initial titration. In some instances it may be desirable to administer separate tablets of either spironolactone or hydrochlorothiazide in addition to spironolactone and hydrochlorothiazide tablets in order to provide optimal individual therapy.

The onset of diuresis with spironolactone and hydrochlorothiazide tablets occurs promptly and, due to prolonged effect of the spironolactone component, persists for two to three days after spironolactone and hydrochlorothiazide tablets are discontinued.

Essential hypertension. Although the dosage will vary depending on the results of titration of the individual ingredients, many patients will be found to have an optimal response to 50 mg to 100 mg each of spironolactone and hydrochlorothiazide daily, given in a single dose or in divided doses.

Concurrent potassium supplementation is not recommended when spironolactone and hydrochlorothiazide tablets are used in the long-term management of hypertension or in the treatment of most edematous conditions, since the spironolactone content of spironolactone and hydrochlorothiazide tablets is usually sufficient to minimize loss induced by the hydrochlorothiazide component.

HOW SUPPLIED

Spironolactone and hydrochlorothiazide tablets, USP are supplied as follows:

Spironolactone and hydrochlorothiazide tablets, 25 mg/25 mg are buff, round, unscored, debossed MP 40.

Bottles of 100

NDC 53489-144-01

Bottles of 500

NDC 53489-144-05

Bottles of 1000

NDC 53489-144-10

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room Temperature]

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

Distributed by: Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512

Rev 12, December 2022

PRINCIPAL DISPLAY PANEL — 25 mg Tablet Bottle Label

PDP-25mg/25mg
(click image for full-size original)
SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE
spironolactone and hydrochlorothiazide tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53489-144
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Spironolactone (Spironolactone) Spironolactone 25 mg
Hydrochlorothiazide (Hydrochlorothiazide) Hydrochlorothiazide 25 mg
Inactive Ingredients
Ingredient Name Strength
anhydrous lactose
silicon dioxide
D&C yellow No. 10
docusate sodium
FD&C yellow no. 6
Aluminum Oxide
magnesium stearate
MICROCRYSTALLINE CELLULOSE
peppermint
POVIDONE, UNSPECIFIED
sodium benzoate
Sodium Starch Glycolate Type A Potato
Product Characteristics
Color WHITE (off-white, buff) Score no score
Shape ROUND Size 10mm
Flavor PEPPERMINT Imprint Code MP;40
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:53489-144-01 100 TABLET in 1 BOTTLE, PLASTIC None
2 NDC:53489-144-05 500 TABLET in 1 BOTTLE, PLASTIC None
3 NDC:53489-144-10 1000 TABLET in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA089534 07/02/1987
Labeler — Sun Pharmaceutical Industries, Inc. (146974886)
Establishment
Name Address ID/FEI Operations
Frontida BioPharm Inc. 080243260 ANALYSIS (53489-144), MANUFACTURE (53489-144), PACK (53489-144)

Revised: 01/2023 Sun Pharmaceutical Industries, Inc.

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