Hydrochlorothiazide (Microzide) is a thiazide diuretic that is used in patients with fluid overload and hypertension as monotherapy or in combination with other drugs.

Hydrochlorothiazide (Microzide) Uses:

• Edema:

  • It is used to treat edoema brought on by heart failure, liver cirrhosis, several types of renal dysfunction such nephrotic syndrome, acute glomerulosclerosis, and chronic renal failure, among others.
  • Additionally, it is employed to treat edoema brought on by corticosteroid and oestrogen medication.
  • It is crucial to remember that spironolactone has mainly taken the position of hydrochlorothiazide in the treatment of edoema for hepatic cirrhosis.
  • The use of loop diuretics like furosemide has essentially superseded the use of hydrochlorothiazide in the therapy of edoema in individuals with renal impairment.

• Hypertension:

  • Management of mild to moderate hypertension
  • Guideline recommendations:
    • In the absence of comorbidities (such as cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High
    • Blood Pressure in Adults suggests that thiazide-like diuretics or dihydropyridine calcium channel blockers are preferred options because of improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
    • ARBs and ACE inhibitors are also suitable for monotherapy.
    • Combination therapy is originally advised for individuals at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease) since it may be necessary to meet blood pressure targets.

• Off Label Use of Hydrochlorothiazide in Adults:

  • Calcium nephrolithiasis.
  • Lithium-induced diabetes insipidus.

Hydrochlorothiazide (Microzide) Dose in Adults

Hydrochlorothiazide (Microzide) Dose in the treatment of Calcium nephrolithiasis (off-label):

• It is given as 50 mg daily in 1 or 2 divided doses.

Hydrochlorothiazide (Microzide) Dose in the treatment of Edema:

• It is administered orally as 25 to 100 mg per day divided into 1 to 2 doses. One may administer sporadically on different days or on three to five days

Hydrochlorothiazide (Microzide) Dose in the treatment of mild fluid retention in heart failure:

• Initially, it is given as 25 mg once or twice a day. The maximum daily dose is 200 mg.

Hydrochlorothiazide (Microzide) Dose in the treatment of Hypertension:

• At first, 12.5 to 25 mg are used orally once per day.
• The maximum dosage is 50 mg per day, which can be given in 1 or 2 divided doses as needed dependent on the patient's response.

Hydrochlorothiazide (Microzide) Dose in Children

Hydrochlorothiazide (Microzide) Dose in the treatment of Bronchopulmonary dysplasia:

• Infants:

  • Oral: It is administered in 2 divided dosages of 3 to 4 mg/kg/day.

Hydrochlorothiazide (Microzide) Dose in the treatment of Edema (diuresis):

• Infants <6 months:

  • Oral: It is administered in divided doses of 1 to 2 mg/kg/day. Some infants, meanwhile, do need 3 mg/kg/day in 2 separate doses.
  • The daily dose cap is 37.5 mg.

• Infants ≥6 months and Children <2 years:

  • • One to two divided dosages of 1 to 2 mg/kg/day are administered orally. The daily dosage cap is 37.5 mg.

• Children ≥2 years:

  • One to two divided dosages of 1 to 2 mg/kg/day are administered orally. 100 is the maximum daily dosage.

• Adolescents:

  • The maximum adult daily dose is 200 mg/day, which is advised for heart failure-related edoema. It is administered orally in doses of 1 to 2 mg/kg/day given in 1 to 2 split doses.

Hydrochlorothiazide (Microzide) Dose in the treatment of Hypertension:

• Manufacturer's labeling:

  • Infants <6 months:

    • Oral:It is administered in divided doses of 1 to 2 mg/kg/day. Some infants, though, might need 3 mg/kg/day in two separate doses. The daily dosage cap is 37.5 mg.

  • Infants ≥6 months and Children <2 years:

    • One to two divided dosages of 1 to 2 mg/kg/day are administered orally. The daily dose cap is 37.5 mg.

  • Children ≥2 years:

    • Oral: It is administered in divided doses of 1 to 2 mg/kg/day. The daily dose cap is set at 100 mg.

• Alternate dosing:

  • Infants, Children, and Adolescents:

    • Oral: Initially it is given as  1 mg/kg/day once a day.
    • It might be increased to a maximum daily dose is 3 mg/kg/day or 50 mg/day, whichever is lower.

Hydrochlorothiazide (Microzide) Dose in the treatment of Hypercalciuria:

• Infants, Children, and Adolescents:

  • Oral: In the beginning, it is administered in divided dosages of 1 to 2 mg/kg/day.
  • Titrate until symptoms disappear and urinary calcium excretion objectives are met.
  • The typical adult dose is 25 to 100 mg/day, with the course of treatment lasting for a full year.

Hydrochlorothiazide (Microzide) Dose in the treatment of Congenital Nephrogenic diabetes insipidus:

• Infants, Children, and Adolescents:

  • Oral: In addition to amiloride, it is administered at a dose of 2 mg/kg/day.
  • Some people do require daily dosages of 3 mg/kg split.
  • The typical dosing range for adults is 25 mg once or twice per day.

Pregnancy Risk Factor B

• Although hydrochlorothiazide can pass the placenta, research on animal reproduction have not revealed any negative effects.
• Use of maternal contraceptives may result in thrombocytopenia, foetal or neonatal jaundice, or other negative effects in adults.
• In healthy pregnancies, thiazide diuretics are not advised for the treatment of edoema.
• If edema is caused by pathologic reasons (as in the patient not pregnant), it can be used. Pay attention.
• Chronic maternal hypertension, if not treated, can lead to adverse outcomes in the infant, mother, and fetus.
• Women who used thiazide diuretics to treat hypertension prior to pregnancy can continue their use.

Use of hydrochlorothiazide during breastfeeding

• Breast milk contains hydrochlorothiazide.
• Hydrochlorothiazide's relative infant dose (RID), is 0.6%-1.2% compared to a infant therapeutic dose of 1–2 mg/kg/day.
• When the RID is less than 10%, breastfeeding is generally acceptable.
• Based on a single case report, the RID for hydrochlorothiazide was estimated using milk concentration of 80ng/mL.
• This results in an estimated 0.012 mg/day daily baby dosage when given through breastfeeding.
• This was accomplished after giving the mother 50 mg of oral chlorothiazide once a day for 3.5 years.
• Hydrochlorothiazide was absent from the newborn serum.
• The potential for serious adverse reactions in breastfeeding infants is a reason the guidelines suggest that you decide whether to stop nursing or discontinue using the drug.
• The significance of the mother's care should be considered when making this choice.
• If you have taken hydrochlorothiazide, you can still breastfeed.
• Large doses of hydrochlorothiazide should be avoided, as they can cause lactation to be impeded.

Hydrochlorothiazide (Microzide) Dose in Kidney Disease:

• The literature doesn't mention changing the dosage. Anuria makes its use contraindicated.

• The following modifications have been suggested.:

  • CrCl ≥10 mL/minute:
    • No dosage modifications are required.
    • Unless used in conjunction with a loop diuretic, usually ineffective when CrCl 30 mL/minute.
  • CrCl <10 mL/minute:
    • It is not advised to use it.

Dose in Liver disease:

The literature doesn't mention changing the dosage. Use cautiously, nevertheless, and keep an eye out for hepatic coma flare-ups.

Side effects of Hydrochlorothiazide (Microzide):

• 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

• Gastrointestinal:

  • Abdominal Cramps
  • Anorexia
  • Constipation
  • Diarrhea
  • Gastric Irritation
  • Nausea
  • Pancreatitis
  • Sialadenitis
  • Vomiting

• Genitourinary:

  • Impotence

• Hematologic & Oncologic:

  • Agranulocytosis
  • Aplastic Anemia
  • Hemolytic Anemia
  • Leukopenia
  • Purpura
  • Thrombocytopenia

• Hepatic:

  • Jaundice

• Hypersensitivity:

  • Anaphylaxis

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Weakness

• Ophthalmic:

  • Transient Blurred Vision
  • Xanthopsia

• Renal:

  • Interstitial Nephritis
  • Renal Failure
  • Renal Insufficiency

• Respiratory:

  • Respiratory Distress
  • Pneumonitis
  • Pulmonary Edema

• Miscellaneous:

  • Fever

Contraindications to Hydrochlorothiazide (Microzide):

• Hypersensitivity to hydrochlorothiazide or any of its components, as well as sulfonamide-derived drugs, is an absolute contraindication.
• Anuria
• It is significant to note that although some product labels specify this prescription should not be taken with other groups of drugs that contain sulfonamides, the scientific validity of this claim has been questioned.

Canadian labeling:Additional contraindications not listed in the US labeling:

• Treatment of severe progressive kidney disease may involve an increase in azotemia or oliguria.
• Breastfeeding
• Studies on allergenic cross-reactivity of thiazide-related diuretics to thiazides are very limited. Cross-sensitivity is possible due to similarities in pharmacologic reactions.

Warnings and precautions

• Electrolyte disturbances:

  • Low serum potassium levels, hypomagnesemia, and hypochloremic acidosis might result from it.
  • The risk of electrolyte abnormalities can be decreased by combining with other medications that preserve electrolytes (such as ACE inhibitors and angiotensin receptor blocking medicines).

• Gout

  • Hydrochlorothiazide can trigger gout in certain patients who have a history of gout or are at risk for chronic renal failure.
  • Doses exceeding 25 mg may increase the risk.

• Hypersensitivity reactions

  • Hydrochlorothiazide may cause hypersensitivity reactions.
  • Patients with a history bronchial or allergy disorder are at greater risk.

• Ocular effects

  • It can cause acute transient myopia or acute angle-closure blindness.
  • These symptoms usually appear within hours to weeks of initiation.
  • Patients suffering from severe visual impairment or ocular pain should stop taking the medication immediately. 
  • If intraocular pressure is not controlled, additional treatments may be necessary.
  • A history of penicillin allergy or sulfonamide allergy could be a risk factor.

• Photosensitivity

  • Photosensitization can occur.

• Allergy to sulfonamide ("sulfa")

  • Wide-ranging contraindications for patients who have previously experienced an adverse reaction to sulfonamides are listed on FDA-approved product labels for drugs that contain sulfonamide chemical groups.
  • Cross-reactivity is possible between members of one class (e.g., two antibiotics sulfonamides).
  • Crossreactivity concerns have been raised for all compounds with the sulfonamide structural.
  • Research has demonstrated that sulfonamides, both non-antibiotic and antibiotic, can react with one another, leading to allergies.
  • Sulfonamides that are not antibiotics are particularly unlikely to result in cross-reactions brought on by the development of antibodies, such as anaphylaxis.
  • Less is known about type IV reactions mediated by T cells, such as the maculopapular skin rash. Based on what is known right now, it is hard to rule out this scenario.
  • Some doctors choose to avoid these classes in cases of severe reactions (Stevens Johnson syndrome/TEN).

• Insufficiency of the adrenal glands:

  • Patients with Addison’s disease should not be treated for high blood pressure by diuretics.
  • To treat hypertension, it is preferable to adjust glucocorticoid or mineralocorticoid therapy.

• Cirrhosis can cause ascites:

  • Hydrochlorothiazide is not recommended for the treatment of ascites caused by cirrhosis.
  • Extreme caution should be taken. Combining it with spironolactone or furosemide could lead to hyponatremia.

• Diabetes:

  • Patients with diabetes mellitus or prediabetes should exercise caution. It is possible to affect glucose control.

• Hepatic impairment

  • Patients who have severe hepatic impairment need to be careful.
  • Avoid acid-base and electrolyte abnormalities in individuals with advanced or severe liver disease.

• Hypercalcemia:

  • Hypercalcemic patients should refrain from using it.

• Hypercholesterolemia:

  • Patients with high or moderate cholesterol levels should exercise caution. 
  • There have been reports of increased cholesterol and triglyceride levels.

• Hypokalemia

  • It is important to monitor hypokalemia closely. Before starting therapy, it is important to correct low potassium levels.

• Parathyroid disease

  • Thiazide diuretics reduce calcium excretion;
  • Long-term use has been associated with pathologic changes in parathyroid glands that are hypercalcemia or hypophosphatemia.
  • It's crucial to cease the medication before testing for parathyroid function.

• Renal impairment

  • Patients with impaired renal function can experience cumulative effects, including azotemia. In severe renal disease, it is not recommended.

• Systemic lupus erythematosus (SLE):

  • It can trigger activation or flare-ups.

Hydrochlorothiazide: Drug Interaction

Monitoring parameters:

• Blood pressure, dizziness, lightheadedness.
• Serum sodium, potassium, BUN, creatinine.
• Photosensitivity testing of the skin
• Skin cancer

Hypertension:The 2017 Guidelines for the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in Adults

• Confirmed hypertension, known cardiovascular disease, or 10-year ASCVD risk (>10%)
  • Attaining a blood pressure of 130/80 mm Hg is advised.
• Confirmed hypertension, but no signs of an increased ASCVD risk
  • It is feasible to have a target blood pressure of 130/80 mm Hg.

Diabetes and hypertensionGuidelines from the American Diabetes Association (ADA).

• Patients aged 18-65 years without ASCVD and a 10-year ASCVD chance 15%
  • Preferably, target blood pressure should be less than 140/90mm Hg.
• Patients aged 18-65 years old with known ASCVD or 10-year ASCVD risks >15%
  • A target blood pressure of 130/80 mm Hg might be feasible, if it's safe to do so.
• Patients over 65 years old (healthy, complex/intermediate):
  • Preferably, target blood pressure is less than 140/90mm Hg.
• Patients over 65 years old (very complex/poor):
  • Aim for a blood pressure reading of 150/90 mm Hg.

How to administer Hydrochlorothiazide (Microzide)?

Oral:

•  To prevent nocturia, administer early in the morning.

• Unless specifically directed by a doctor, take the final dose of a multiple-dose regimen no later than 6 PM.

Mechanism of action of Hydrochlorothiazide (Microzide):

It increases the excretion of sodium, water, potassium, and hydrogen ions by inhibiting sodium reabsorption in the distal tubules.

The onset of action:

• Diuresis: Infants: 2 to 6 hours.
• In Adults: ~2 hours

Peak effect:

• 4 to 6 hours

Duration:

• Infants: 8 hours.
• In Adults: 6 to 12 hours

Absorption:

• Well absorbed. Its absorption is reduced in patients with CHF.

Protein binding:

• ~40% to 68%

Metabolism:

• Not metabolized

Bioavailability:

• 65% to 75%

Half-life elimination:

• ~6 to 15 hours

Time to peak:

• ~1 to 5 hours

Excretion:

• Urine (≥61% as unchanged drug)

International Brand Names of Hydrochlorothiazide:

• Microzide
• APO-Hydro
• BIO-Hydrochlorothiazide
• MINT-Hydrochlorothiazide
• PMS-Hydrochlorothiazide
• TEVA-Hydrochlorothiazide
• Urozide
• Acortiz
• Acuren
• Apo-Hydro
• BPzide
• Chlothia
• Clorana
• Di-Ertride
• Di-Eudrin
• Dichlorzid
• Dichlotride
• Didralin
• Disalunil
• Disothiazide
• Dithiazide
• Diubiz
• Diurace
• Diures
• Diuret-P
• Diuretyk
• Diurex
• Diurix
• Diursan
• Diuzid
• Esidrex
• Esidrix
• C.T.
• HCT
• HCTZ 25
• Hidroronol
• Hidrosaluretil
• Hipotiazyd
• HTZ
• Hychlozide
• Hydrex
• Hydro-Saluric
• Hydrochlorothiazidum
• Hydrochlorzide
• Hydromed
• Hydrozide
• Hypezide
• Hypothiazid
• Hytaz
• Lonpra
• Maschitt
• Modiur
• Monozide
• Newtolide
• Pantemon
• Ridaq
• Rofucal
• Staplex
• Tandiur
• Tiazid
• Unazid
• Urilzid
• Varidrex

Hydrochlorothiazide Brand Names in Pakistan: