Hydrochlorothiazide / Spironolactone Side Effects

Medically reviewed by Drugs.com. Last updated on Mar 27, 2025.

Applies to hydrochlorothiazide / spironolactone: oral tablet.

Important warnings This medicine can cause some serious health issues

Oral route (tablet)

This drug has been reported to be tumorigenic in rat chronic toxicity studies.

Use this drug only as indicated.

Fixed-dose spironolactone/hydrochlorothiazide is not indicated for the initial treatment of edema or hypertension.

Serious side effects

Along with its needed effects, hydrochlorothiazide / spironolactone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking hydrochlorothiazide / spironolactone:

Incidence not known

• back or leg pains
• blistering, peeling, or loosening of the skin
• bloody or black, tarry stools
• bloody or cloudy urine
• blue lips and fingernails
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or tightness
• clay-colored stools
• clear or bloody discharge from the nipple
• confusion
• cough or hoarseness
• dark urine
• decreased appetite
• diarrhea
• difficult, fast, or noisy breathing
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast or irregular heartbeat
• fever with or without chills
• flushed, dry skin
• fruit-like breath odor
• general body swelling
• general feeling of discomfort or illness
• greatly decreased frequency of urination or amount of urine
• hives or welts, skin rash
• increased hunger
• increased thirst
• inverted nipple
• joint pain, stiffness, or swelling
• lower back or side pain
• lump in the breast or under the arm
• muscle cramps or pain
• nausea and vomiting
• numbness, tingling, pain, or weakness in the hands, feet, or lips
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent non-healing sore
• pink growth
• pinpoint red or purple spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red, irritated eyes
• reddish patch or irritated area
• redness or swelling of the breast
• redness, soreness, or itching skin
• seizures
• shiny bump
• sore on the skin of the breast that does not heal
• sores, ulcers, or white spots on the lips or in the mouth
• stomach cramping, burning, or tenderness
• swelling of the face, hands, fingers, feet, or lower legs
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• trembling
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• white, yellow or waxy scar-like area
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking hydrochlorothiazide / spironolactone:

Symptoms of overdose

• difficulty with sleeping
• disorientation
• drowsiness to profound coma
• hallucination
• lethargy
• lightheadedness
• mood or other mental changes
• rash with flat lesions or small raised lesions on the skin

Other side effects

Some side effects of hydrochlorothiazide / spironolactone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• absent, missed, or irregular menstrual periods
• bleeding after menopause
• burning feeling in the chest or stomach
• discoloration of the skin
• feeling of constant movement of self or surroundings
• inability to have or keep an erection
• increased sensitivity of the skin to sunlight
• muscle spasm
• restlessness
• sensation of spinning
• severe sunburn
• stomach upset
• stopping of menstrual bleeding
• swelling of the breasts or breast soreness in both females and males

For healthcare professionals

Applies to hydrochlorothiazide / spironolactone: oral tablet.

Endocrine adverse events

Spironolactone:

• Frequency not reported: Gynecomastia^[Ref]

Other

Hydrochlorothiazide:

• Frequency not reported: Weakness, fever, vertigo

Spironolactone:

• Frequency not reported: Breast pain, fever^[Ref]

Cardiovascular

Hydrochlorothiazide:

• Frequency not reported: Hypotension, orthostatic hypotension, necrotizing angitis, vasculitis

Spironolactone:

• Frequency not reported: Vasculitis^[Ref]

Hepatic

Hydrochlorothiazide:

• Frequency not reported: Pancreatitis, intrahepatic cholestatic jaundice

Spironolactone:

• Frequency not reported: Mixed cholestatic/hepatocellular toxicity^[Ref]

Gastrointestinal

Hydrochlorothiazide:

• Frequency not reported: Diarrhea, vomiting, sialoadenitis, cramping, constipation, gastric irritation, nausea

Spironolactone:

• Frequency not reported: Gastric bleeding, ulceration, gastritis, diarrhea, cramping, nausea, vomiting^[Ref]

Metabolic

Hydrochlorothiazide:

• Frequency not reported: Anorexia, electrolyte imbalance, hyperglycemia, hyperuricemia

Spironolactone:

• Frequency not reported: Hyperkalemia, electrolyte disturbances^[Ref]

Ocular

Hydrochlorothiazide:

• Frequency not reported: Acute myopia, acute angle closure glaucoma, transient blurred vision, xanthopsia^[Ref]

Hematologic

Hydrochlorothiazide:

• Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia

Spironolactone:

• Frequency not reported: Leukopenia, agranulocytosis, thrombocytopenia^[Ref]

Immunologic

Hydrochlorothiazide:

• Frequency not reported: Anaphylactic reactions

Spironolactone:

• Frequency not reported: Anaphylactic reactions^[Ref]

Dermatologic

Hydrochlorothiazide:

• Frequency not reported: Cutaneous vasculitis, photosensitivity, urticaria, rash, purpura, erythema multiforme, pruritus

Spironolactone:

• Frequency not reported: Urticaria, maculopapular or erythematous cutaneous eruptions, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, alopecia, pruritus

Postmarketing: Non-melanoma skin cancer^[Ref]

Respiratory

Hydrochlorothiazide:

• Frequency not reported: Pneumonitis, pulmonary edema^[Ref]

Genitourinary

Hydrochlorothiazide:

• Frequency not reported: Glycosuria

Spironolactone:

• Frequency not reported: Inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding^[Ref]

Musculoskeletal

Hydrochlorothiazide:

• Frequency not reported: Muscle spasm

Spironolactone:

• Frequency not reported: Leg cramps^[Ref]

Nervous system

Hydrochlorothiazide:

• Frequency not reported: Paresthesias, dizziness, headache

Spironolactone:

• Frequency not reported: Lethargy, ataxia, dizziness, headache, drowsiness^[Ref]

Psychiatric

Hydrochlorothiazide:

• Frequency not reported: Restlessness

Spironolactone:

• Frequency not reported: Mental confusion^[Ref]

Renal

Hydrochlorothiazide:

• Frequency not reported: Renal failure, renal dysfunction, interstitial nephritis

Spironolactone:

• Frequency not reported: Renal dysfunction, renal failure^[Ref]

Oncologic

Spironolactone:

• Frequency not reported: Carcinoma of the breast^[Ref]

Further information

Hydrochlorothiazide/spironolactone side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

Medical Disclaimer