Side Effects of Zaroxolyn (metolazone)

Zaroxolyn (metolazone) is a diuretic ("water pill") used to treat high blood pressure and fluid accumulation. It works by blocking salt and fluid retention by the kidneys, thereby increasing urinary output of salt and water (diuresis).

Although it is not a true thiazide, Zaroxolyn is chemically related to the thiazide class of diuretics and works in a similar manner. Zaroxolyn is the original formulation of metolazone, and Diulo is similar.

The absorption of these two drugs is relatively incomplete. Mykrox has more complete absorption. Therefore, less Mykrox needs to be given to have the same effects as a larger dose of Zaroxolyn or Diulo. 

Common side effects of Zaroxolyn include

• low blood potassium (hypokalemia),
• low blood sodium (hyponatremia),
• low blood magnesium (hypomagnesemia),
• high blood calcium (hypercalcemia),
• dizziness,
• lightheadedness,
• headache,
• fatigue,
• nausea,
• vomiting,
• abdominal pain, and
• constipation.

Serious side effects of Zaroxolyn include

• increased uric acid in the blood which can precipitate gout (rare) and
• increased blood sugar in people with diabetes.

Drug interactions of Zaroxolyn include "loop" diuretics such as furosemide, bumetanide, and torsemide, because Zaroxolyn can also reduce blood potassium and magnesium levels which can lead to heart rhythm abnormalities, especially in patients taking digoxin. Zaroxolyn reduces excretion of lithium by the kidneys and can lead to lithium toxicity.

Steroids (for example, hydrocortisone) and nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the effectiveness of Zaroxolyn by interfering with the excretion of salt and water.

Zaroxolyn should not be used during pregnancy unless absolutely necessary.

Zaroxolyn is excreted in breast milk. Intense diuresis using Zaroxolyn may reduce the production of milk. Otherwise Zaroxolyn is considered safe to use during breastfeeding if required by the mother.

Metolazone generally is well tolerated. Common side effects of metolazone are:

• Hypokalemia (low blood potassium),
• hyponatremia
• (low blood sodium), and
• hypomagnesemia (low blood magnesium).
• Hypercalcemia (high blood calcium)

About 1 out of every 10 patients report dizziness, lightheadedness, and headache. Fatigue has been reported in 1 out of every 25 patients. About 1 out of every 50 patients reports:

• nausea,
• vomiting,
• abdominal pain, or
• constipation.

Thiazide diuretics, which are chemically related to metolazone, are known to increase the amount of uric acid in the blood. Precipitation of gout (which is associated with high uric acid) is rare. Metolazone can increase blood sugar in people with diabetes.

Zaroxolyn is usually well tolerated, and most reported adverse reactions have been mild and transient. Many Zaroxolyn related adverse reactions represent extensions of its expected pharmacologic activity and can be attributed to either its antihypertensive action or its renal/metabolic actions. The following adverse reactions have been reported. Several are single or comparably rare occurrences. Adverse reactions are listed in decreasing order of severity within body systems.

Cardiovascular

Chest pain/discomfort, orthostatic hypotension, excessive volume depletion, hemoconcentration, venous thrombosis, palpitations.

Central And Peripheral Nervous System

Syncope, neuropathy, vertigo, paresthesias, psychotic depression, impotence, dizziness/lightheadedness, drowsiness, fatigue, weakness, restlessness (sometimes resulting in insomnia), headache.

Dermatologic/Hypersensitivity

Toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome, necrotizing angiitis (cutaneous vasculitis), skin necrosis, purpura, petechiae, dermatitis (photosensitivity), urticaria, pruritus, skin rashes.

Gastrointestinal

Hepatitis, intrahepatic cholestatic jaundice, pancreatitis, vomiting, nausea, epigastric distress, diarrhea, constipation, anorexia, abdominal bloating, abdominal pain.

Hematologic

Aplastic/hypoplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic

Hypokalemia, hyponatremia, hyperuricemia, hypochloremia, hypochloremic alkalosis, hyperglycemia, glycosuria, increase in serum urea nitrogen (BUN) or creatinine, hypophosphatemia, hypomagnesemia, hypercalcemia.

Musculoskeletal

Joint pain, acute gouty attacks, muscle cramps or spasm.

Other

Transient blurred vision, chills, dry mouth.

In addition, adverse reactions reported with similar antihypertensive-diuretics, but which have not been reported to date for Zaroxolyn include: bitter taste, sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These reactions should be considered as possible occurrences with clinical usage of Zaroxolyn.

Whenever adverse reactions are moderate or severe, Zaroxolyn dosage should be reduced or therapy withdrawn.

Diuretics

Furosemide and probably other loop diuretics given concomitantly with metolazone can cause unusually large or prolonged losses of fluid and electrolytes.

Other Antihypertensives

When Zaroxolyn Tablets are used with other antihypertensive drugs, care must be taken, especially during initial therapy. Dosage adjustments of other antihypertensives may be necessary.

Alcohol, Barbiturates, And Narcotics

The hypotensive effects of these drugs may be potentiated by the volume contraction that may be associated with metolazone therapy.

Digitalis Glycosides

Diuretic-induced hypokalemia can increase the sensitivity of the myocardium to digitalis. Serious arrhythmias can result.

Corticosteroids Or ACTH

May increase the risk of hypokalemia and increase salt and water retention.

Lithium

Serum lithium levels may increase.

Curariform Drugs

Diuretic-induced hypokalemia may enhance neuromuscular blocking effects of curariform drugs (such as tubocurarine) – the most serious effect would be respiratory depression which could proceed to apnea. Accordingly, it may be advisable to discontinue Zaroxolyn three days before elective surgery.

Salicylates And Other Non-Steroidal Anti-Inflammatory Drugs

May decrease the antihypertensive effects of Zaroxolyn Tablets.

Sympathomimetics

Metolazone may decrease arterial responsiveness to norepinephrine, but this diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Insulin And Oral Antidiabetic Agents

See prescribing information on glucose tolerance.

Methenamine

Efficacy may be decreased due to urinary alkalizing effect of metolazone.

Anticoagulants

Metolazone, as well as other thiazide-like diuretics, may affect the hypoprothrombinemic response to anticoagulants; dosage adjustments may be necessary.