February 25, 2017
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"What are diuretics and how do they work?

The amount of fluid (water) retained by the body is controlled primarily by the kidneys. This occurs due to the kidney's ability to control the retention and elimination of sodium and chlorid"...



Side Effects


Adverse experience information is available from more than 14 years of accumulated marketing experience with other formulations of metolazone for which reliable quantitative information is lacking and from controlled clinical trials with MYKROX (metolazone) from which incidences can be calculated.

In controlled clinical trials with MYKROX (metolazone) , adverse experiences resulted in discontinuation of therapy in 6.7-6.8% of patients given ½ to 1 mg of MYKROX (metolazone) .

Adverse experiences occurring in controlled clinical trials with MYKROX (metolazone) with an incidence of > 2%, whether or not considered drugrelated, are summarized in the following table.

Incidence of Adverse Experiences Volunteered or Elicited (by Patient in Percent)*

n = 226†
Dizziness (lightheadedness) 10.2
Headaches 9.3
Muscle Cramps 5.8
Fatigue (malaise, lethargy, lassitude) 4.4
Joint Pain, swelling 3.1
Chest Pain (precordial discomfort) 2.7
* Percent of patients reporting an adverse experience one or more times.
† All doses combined (½, 1, and 2 mg).

Some of the adverse effects reported in association with MYKROX (metolazone) also occur frequently in untreated hypertensive patients, such as headache and dizziness, which occurred in 14.8 and 7.4% of patients in a smaller parallel placebo group.

The following adverse effects were reported in less than 2% of the MYKROX (metolazone) treated patients.


Cold extremities, edema, orthostatic hypotension, palpitations.

Central and Peripheral Nervous System

Anxiety, depression, dry mouth, impotence, nervousness, neuropathy, weakness, “weird” feeling.


Pruritus, rash, skin dryness.

Eyes, Ears, Nose, Throat

Cough, epistaxis, eye itching, sinus congestion, sore throat, tinnitus.


Abdominal discomfort (pain, bloating), bitter taste, constipation, diarrhea, nausea, vomiting.




Back pain.

Other Adverse Experiences

Adverse experiences reported with other marketed metolazone formulations and most thiazide diuretics, for which quantitative data are not available, are listed in decreasing order of severity within body systems. Several are single or rare occurrences.


excessive volume depletion, hemoconcentration, venous thrombosis.

Central and Peripheral Nervous System

syncope, paresthesias, drowsiness, restlessness (sometimes resulting in insomnia).


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


hepatitis, intrahepatic cholestatic jaundice, pancreatitis, anorexia, nausea, diarrhea, abdominal pain.


aplastic (hypoplastic) anemia, agranulocytosis, leukopenia, thrombocytopenia.


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


acute gouty attacks.


transient blurred vision, chills.

In addition, rare adverse experiences reported in association with similar antihypertensive-diuretics but not reported to date for metolazone include: sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These experiences could occur with clinical use of metolazone.

Read the Mykrox (metolazone) Side Effects Center for a complete guide to possible side effects



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

Other Antihypertensives

When MYKROX (metolazone) 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.


Serum lithium levels may increase (see WARNINGS).

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 MYKROX® Tablets (metolazone tablets, USP) three days before elective surgery.

Salicylates and Other Non-Steroidal Anti-Inflammatory Drugs

May decrease the antihypertensive effects of MYKROX Tablets.


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 Glucose Tolerance under PRECAUTIONS, General.


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


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

Drug/Laboratory Test Interactions

None reported.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 5/4/2009

Side Effects

Report Problems to the Food and Drug Administration


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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