A thiazide diuretic medication called metolazone (Zaroxolyn) is used to treat the symptoms of edoema brought on by renal and heart failure.

Metolazone Indications:

• Edema:

  • Metolazone is used to treat edoema brought on by heart failure or renal disorders, such as nephrotic syndrome and ailments with impaired renal function.

Metolazone Dose in Edema due to heart failure (adjunctive agent) (off-label dose):

It is noteworthy that patients with heart failure who have decreased or retained ejection fraction prefer a loop diuretic like furosemide for the first treatment for edoema. It is appropriate to add a thiazide-type diuretic if IV loop diuretic therapy alone is unable to improve congestive symptoms in hospitalized patients with acute decompensated heart failure (e.g., metolazone).

• It may be administered orally. starting at 2.5 mg once a day, with a 20 mg daily dosage maximum. Depending on the patient's individual diuretic needs, the dose frequency may need to be changed (for example, weekly or every other day administration).

Metolazone Dose in the treatment of Edema due to renal disease:

• Initially, it can be given orally as 5 to 20 g daily.

Metolazone Dose in refractory edema: Limited data available:

• Infants, Children, and Adolescents:

  • When taken orally, its typical dosage range for maintenance therapy is 0.2 to 0.4 mg/kg/day split every 12 to 24 hours in conjunction with a loop diuretic. Adults should not exceed a daily intake of 20 mg.

Note: The trials only provided scant information on the effectiveness of metolazone in treating babies and toddlers. The response might be impacted by the underlying illness status, renal function, and continuing treatments. The manufacturer reports that in certain pediatric patients, a lower dosage of 0.05 to 0.1 mg/kg once a day has also been seen to cause weight loss and increase urine production.

Metolazone Pregnancy Category: B

• Metolazone was shown to be able to cross the placental boundary and has been presented in cord blood.
• Low sugars, electrolyte abnormalities, and icterus are all reported adverse effects on the newborn or fetus following maternal use.
• It is not recommended to be used for edema in normal pregnancies. It might be used if edema is caused by pathologic factors (as in the patient is not pregnant), but strict monitoring is necessary.

Metolazone can be used during breastfeeding

• This drug is found in milk.
• The manufacturer suggests that a clinical decision be made regarding whether there are any serious adverse reactions in infants and whether breastfeeding should be stopped.

Metolazone Dose in Kidney Disease:

According to the labeling provided by the manufacturer, no dosage modifications are necessary. Use with caution in those with severe renal sickness, nevertheless, as the majority of the medication is removed by the renal route and plasma levels may increase.

Dose in Liver disease:

No dose adjustments are required in liver disease however absolutely contraindicated in hepatic encephalopathy. 

Side effects of Metolazone:

• Dermatologic:

  • Skin Photosensitivity
  • Skin Rash
  • Toxic Epidermal Necrolysis
  • Urticaria
  • Pruritus
  • Skin Necrosis
  • Stevens-Johnson Syndrome

• Cardiovascular:

  • Venous Thrombosis
  • Necrotizing Angiitis
  • Orthostatic Hypotension
  • Palpitations
  • Chest Discomfort
  • Chest Pain
  • Syncope

• Endocrine & Metabolic:

  • Hypochloremia
  • Hypochloremic Alkalosis
  • Hypercalcemia
  • Hyperglycemia
  • Hypophosphatemia
  • Hypovolemia
  • Hyperuricemia
  • Hypokalemia
  • Glycosuria
  • Gout
  • Hypomagnesemia
  • Hyponatremia
•  

• Renal:

  • Increased Blood Urea Nitrogen

• Central Nervous System:

  • Drowsiness
  • Fatigue
  • Headache
  • Chills
  • Restlessness
  • Vertigo
  • Depression
  • Dizziness
  • Neuropathy
  • Paresthesia

• Hematologic & Oncologic:

  • Hypoplastic Anemia
  • Thrombocytopenia
  • Agranulocytosis
  • Aplastic Anemia
  • Leukopenia
  • Petechia
  • Hemoconcentration
  • Purpura
•  

• Gastrointestinal:

  • Bloating
  • Nausea
  • Constipation
  • Diarrhea
  • Abdominal Pain
  • Anorexia
  • Vomiting
  • Xerostomia
  • Epigastric Distress
  • Pancreatitis

• Neuromuscular & Skeletal:

  • Muscle Cramps
  • Muscle Spasm
  • Arthralgia
  • Weakness

• Genitourinary:

  • Impotence

• Hepatic:

  • Cholestatic Jaundice
  • Hepatitis

• Ophthalmic:

  • Transient Blurred Vision

Contraindications to Metolazone:

Once hypersensitivity to metolazone has been established, this drug is completely contraindicated. Studies have not provided any evidence of cross-reactivity between thiazide diuretics and allergenic substances. Cross-sensitivity is possible due to similarities in biochemical properties, actions, and biochemical reactions. However, this cannot be ruled out with any degree of acuity.

Warnings and precautions

• • Electrolyte disturbances:

    • After the first dose, there is a high chance of electrolyte disturbances.
    • Hypomagnesemia, hyperchloremic alkalosis, or increased calcium can all occur.

  • Hypersensitivity

    • A possible anaphylactic reaction may also occur.

  • Orthostatic hypotension

    • Orthostatic hypotension can occur in patients who take metolazone.
    • The use of Ethanol, barbiturates, or narcotics in conjunction with orthostatic hypotensive episodes can increase the likelihood of these episodes.
    • The treating physician should immediately stop using such agents.
    • Hypotensive episodes, however, should be monitored closely if they are required.

  • Photosensitivity

    • Photosensitization might occur.

  • Effects on the renal system:

    • It is possible to get low urine output or azotemia.

  • Allergy to sulfonamide ("sulfa")

    • This medication should not be used by patients who are allergic to sulfonamides. The labeling is FDA-approved.
    • Cross-reactivity is possible between members of one class (e.g., two antibiotics sulfonamides).
    • Concerns about cross-reactivity have been elevated for all substances with a sulfonamide structure.
    • Cross-reactivity is suggested by an enhanced understanding of allergic mechanisms. between antibiotics in the sulfonamide class and non-antibiotic sulfonamides. This could mean that such reactions might not occur, or at best, are very unlikely.
    • Nonantibiotic sulfonamides will not cause anaphylaxis through mechanisms of cross-reaction.
    • Despite the lack of knowledge around T-cell-mediated type IV responses such as maculopapular skin rash, it is impossible to rule out the possibility based on current knowledge.
    • Many clinicians avoid exposure to these classes in cases of severe reactions, such as Stevens-Johnson syndrome and TEN.

  • Insufficiency of the adrenals:

    • Patients with primary adrenal dysfunction should not use diuretics to lower blood pressure. This is because of the possibility of severe hyponatremia (Addison disease).
    • Patients who are on glucocorticoid and mineralocorticoid therapy should have their dosage adjusted, especially if they are being taken with antihypertensives.

  • Bariatric surgery

    • Avoid dehydration during this procedure. Avoid diuretics during the first 24 hours after bariatric surgery. They can cause AKI. Dehydration and electrolyte disturbances can occur. If oral fluid intake goals have been met, diuretics can be resumed if necessary.

  • Diabetes:

    • Patients with diabetes should be aware that Thiazide diuretics may cause hyperglycemia.

  • Gout

    • Hyperuricemia is possible and can lead to gout.

  • Hepatic impairment

    • Hepatic impairment can be dangerous so it is important to exercise caution.

  • Hypokalemia

    • Thiazide diuretics can make hypokalemia worse.

  • Renal impairment

    • If you have previously had renal impairment, a Thiazide diuretic may worsen oliguria or azotemia.

  • Systemic lupus erythematosus (SLE):

    • SLE activation or exacerbation can occur.

Metolazone: 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 and RFTs
• uric acid.
• fluid balance and blood pressure both in standing and sitting positions.

How to administer Metolazone?

it is administered orally as a single daily dose with or without food. Therapy should be taken early in the day to avoid nocturia. 

Mechanism of action of Metolazone:

It inhibits sodium reabsorption from the distal tubules, causing an increase in the excretion of water and sodium, as well as potassium and hydrogen ions.

Protein binding:

• 95%.

Half-life elimination:

• 8 to 14 hours.

The onset of action:

• Diuresis: ~60 minutes.

Excretion:

• Urine (80%).

Duration:

• ≥24 hours.

Bioavailability:

• 65%.

International Brand Names of Metolazone:

• Zaroxolyn
• Barolyn
• Birobin
• Demafight
• Diulo
• Effectinix
• Merozolyn
• Metenix 5
• Metolaz
• Metos
• Metoz
• Mycros
• Mykyo
• Oldren
• Pavedal
• Rifky
• Rixia
• Zaroxolyn

Metolazone Brand Names in Pakistan:

No Brands Available in Pakistan.