Chlorothiazide inhibits sodium and water reabsorption in the distal tubules resulting in salt and water loss from the body. It is thus used to treat the following conditions:

• Edematous and fluid overloaded states
• It may be used to treat Hypertension as monotherapy (or in combination with other medicines ) in the absence of other comorbid conditions like diabetes, kidney disease, ischemic heart disease, and cerebrovascular disease.

Chlorothiazide Dose in Adults

• Dose in Hypertension:
  • 500 to 2,000 mg per day once or twice daily.

• Dose in patients with Edema:
  • 250 to 500 mg orally once or twice daily to a maximum daily dose of 1,000 mg.
  • 500 to 1,000 mg intravenous once a day in combination with a loop diuretic

Chlorothiazide Dose in Childrens

• For diuresis, heart failure, and hypertension:
  • Infants, Children, and Adolescents:
    • 10 to 40 mg/kg/day orally once or twice daily to a maximum daily dose of
      • 375 mg/day in infants and children less than 2 years of age,
      • 1000 mg in children older than 2 years of age, and
      • 2000 mg daily in adolescents
    • 5 to 10 mg/kg/day intravenous in one or two daily divided doses to a maximum dose of 500 mg/dose.

• Dose in central Diabetes insipidus:
  • Infants:
    • 10 mg/kg/day in two divided doses. The dose may be incrementally increased to a target urine osmolality of 100 to 150 mOsm/L.

Pregnancy Risk Factor C

• The placental barrier is crossed by chlorothiazide and can cause neonatal jaundice or thrombocytopenia.
• Women with hypertension may need thiazide diuretics during pregnancy. It should not be used to treat edema caused by pregnancy

Chlorothiazide use during breastfeeding:

• Breastmilk contains chlorothiazide, which can be excreted in this substance.
• This could lead to serious adverse drug reactions in the child.
• You should stop using it while you are breastfeeding. 
• Nursing mothers should avoid diuretics as they can reduce milk production.

Chlorothiazide Dose in Kidney Disease:

• It is usually not effective in patients with a CrCl of less than 30 mL/minute and is, therefore, combined with a loop diuretic.
• Patients with a CrCl of less the 10 mL/minute should avoid the drug.

Chlorothiazide Dose in Liver Disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease, however, it should be used with caution in advanced liver disease.

Side Effects of Chlorothiazide:

• Cardiovascular:
  • Hypotension
  • Necrotizing angiitis
  • Orthostatic hypotension
• Central nervous system:
  • Dizziness
  • Headache
  • Paresthesia
  • Restlessness
  • Vertigo
• Dermatologic:
  • Alopecia
  • Erythema multiforme
  • Exfoliative dermatitis
  • Skin photosensitivity
  • Skin rash
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Urticaria
• Endocrine & metabolic:
  • Glycosuria
  • Hypercalcemia
  • Hyperglycemia
  • Hyperuricemia
  • Hypochloremic alkalosis
  • Hypokalemia
  • Hypomagnesemia
  • Hyponatremia
  • Increased serum cholesterol
  • Increased serum triglycerides
• Gastrointestinal:
  • Abdominal cramps
  • Anorexia
  • Constipation
  • Diarrhea
  • Gastric irritation
  • Nausea
  • Pancreatitis
  • Sialadenitis
  • Vomiting
• Genitourinary:
  • Hematuria
  • Impotence
• Hematologic & oncologic:
  • Agranulocytosis
  • Aplastic anemia
  • Hemolytic anemia
  • Leukopenia
  • Purpura
  • Thrombocytopenia
• Hepatic:
  • Jaundice
• Hypersensitivity:
  • Anaphylaxis
• Neuromuscular & skeletal:
  • Muscle spasm
  • Systemic lupus erythematosus
  • Weakness
• Ophthalmic:
  • Blurred vision
  • Xanthopsia
• Renal:
  • Interstitial nephritis
  • Renal failure
  • Renal insufficiency
• Respiratory:
  • Pneumonitis
  • Pulmonary edema
  • Respiratory distress
• Miscellaneous:
  • Fever

Contraindication to chlorothiazide include:

• Allergy or sensitivity to chlorothiazide, any sulfonamide-derived drug, or any component in the formulation
• Anuria is a urine volume of less than 100ml within the last 24 hours.

Warnings and Precautions

• Electrolyte disturbances:
  • It alters blood electrolytes, causing hypercalcemia and hyponatremia as well as hypokalemia, hypochloremic acidosis, hypokalemia, and hypomagnesemia.
• Orthostatic hypotension
  • This can lead to postural hypotension, especially when combined with concomitant alcohol.
• Photosensitivity
• Allergy to sulfonamide ("sulfa drug")
  • Although, the FDA recommends avoiding chlorothiazide in patients allergic to sulfa drugs, however, studies do not indicate any cross-reactivity.
  • Patients with severe reactions should avoid it.
• Insufficiency of the adrenals:
  • Patients suffering from primary adrenal insufficiency need to avoid chlorothiazide. It may be necessary to adjust the dose of steroid.
• Diabetes:
  • It may impair glucose metabolism and should be used with caution in patients with diabetes mellitus.
• Gout
  • It may precipitate gout and should be used with caution in patients with hyperuricemia.
• Hepatic impairment
  • Patients with liver disease should not take it. Hypokalemia due to excessive chlorothiazide may lead to hepaticencephalopathy.
• Hypercalcemia:
  • Chlorothiazide should not be used in patients with hypercalcemia.
• Hypercholesterolemia:
  • This could lead to elevated blood levels, especially of triglyceride.
• Hypokalemia
  • Before using hypokalemia, it must be corrected
• Renal impairment
  • Patients with impaired renal function should be cautious.
• Systemic lupus, erythematosus
  • It could cause SLE due to drug-induced side effects 

Chlorothiazide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Serum electrolytes,
• renal function,
• blood pressure;
• assess weight,
• intake and output reports daily to determine fluid loss

How to Administer Chlorothiazide?

• Administer the drug as an intravenous infusion.
• It should not be administered via intramuscular or SubQ route.
• Extravasation of the drug must be avoided.

Mechanism of action of Chlorothiazide:

• It acts by blocking the reabsorption sodium and chloride from the distal tubules, resulting in their expulsion along with water. 
• It is possible to also lose potassium, hydrogen ions and magnesium.

TheStart of action The oral tablet takes approximately 2 hours, while the intravenous formulation takes about 15 minutes.

For the oral drug to reach its peak, it can take up to 4 hours while for the IV drug, it can take just 15 minutes.

The oral drug's duration of action isIt can take between 6 and 12 hours for intraveneous forms, while it takes about 3 hours. 

It is not metabolized and poorly absorbed. 

Its bioavailability ranges from 9% to 56%.

Half-life is the time it takes to get rid of the drug.

It is excreted mostly via urine.

International Brands of Chlorothiazide:

• Azide
• Chlorosal
• Chlotride
• Disalunil
• Diurilix
• Diurone
• Diurosulfona
• Hydrochlorothiazidum
• Niagar
• Saluretil
• Saluric
• Salutrid
• Urinex

Chlorothiazide Brands in Pakistan:

No brands available in Pakistan