Applies to ketoconazole: oral tablet.

Serious side effects of Ketoconazole

Along with its needed effects, ketoconazole 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 ketoconazole:

Rare

• Back, leg, or stomach pains
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in color vision
• change in the ability to see colors, especially blue or yellow
• chest pain
• chills
• confusion
• cough
• dark urine
• difficulty seeing at night
• difficulty swallowing
• dizziness
• fast heartbeat
• fever
• general body swelling
• headache
• hoarseness
• increased sensitivity of the eyes to sunlight
• irritation
• joint pain, stiffness, or swelling
• light-colored stools
• loss of appetite
• mood or mental changes
• nausea or vomiting, severe
• nosebleeds
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• skin rash, hives, itching
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swelling of the eyelids, face, lips, hands, or feet
• swollen glands
• tightness in the chest
• trouble sleeping
• troubled breathing or swallowing
• unusual bleeding or bruising
• unusual tiredness or weakness
• vision changes
• yellow eyes or skin

Other side effects of Ketoconazole

Some side effects of ketoconazole 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:

Rare

• Change in number of sperm and their ability to move
• decreased interest in sexual intercourse
• diarrhea
• hair loss or thinning of the hair
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• sleepiness or unusual drowsiness
• swelling of the breasts or breast soreness for both female and male

For Healthcare Professionals

Applies to ketoconazole: compounding powder, oral tablet.

Hepatic

Ketoconazole therapy has commonly been associated with transient elevations in liver enzymes, which have resolved despite continued therapy.

Serious hepatotoxicity has been reported with both high doses for short durations and low doses for long therapy durations. Hepatic injury has usually (but not always) been reversible with discontinuation of ketoconazole therapy. Hepatitis has been reported in children.

Hepatotoxicity has been reported with oral ketoconazole rechallenge.

Severe hepatotoxicity (hepatocellular, cholestatic, or mixed) generally occurred after 1 or 2 months of therapy. Hepatic function usually returned to normal within 1 month, but cases of hepatic failure and death have occurred.^[Ref]

Frequency not reported: Hepatitis, jaundice, abnormal hepatic function, hepatotoxicity, transient elevations of liver enzymes, severe hepatotoxicity (hepatocellular, cholestatic, or mixed)

Postmarketing reports: Serious hepatotoxicity including cholestatic hepatitis, biopsy-confirmed hepatic necrosis, cirrhosis, hepatic failure (including cases resulting in death or requiring liver transplantation)^[Ref]

Cardiovascular

Frequency not reported: Orthostatic hypotension, QT interval prolongation (sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes)^[Ref]

Endocrine

Ketoconazole inhibits hydroxylation of deoxycortisol, which results in diminished cortisol production, especially when given in divided doses. In some patients, symptomatic adrenal insufficiency may occur, presenting with hyponatremia, hyperkalemia, hypotension, lethargy, depression, and malaise.

A 77-year-old male with prostate cancer experienced adrenal crisis coincident with ketoconazole therapy. He presented with progressive right lower extremity weakness, debilitating low back pain, and a serum prostate-specific antigen level of 78.8 ng/mL. He was given ketoconazole 200 mg orally four times daily to reduce serum testosterone levels. Nine days after initiating ketoconazole therapy, he experienced generalized weakness, abdominal pain, nausea with vomiting, and severely diminished mentation. The urology service was advised of the patient's admission and suggested that adrenal insufficiency related to high-dose ketoconazole therapy should be considered in the differential diagnosis. However, a serum cortisol level was not obtained prior to steroid treatment. An ACTH stimulation test performed 2 days later showed no evidence of underlying adrenal insufficiency when the patient was no longer being given ketoconazole.^[Ref]

Rare (less than 0.1%): Hypothyroidism

Frequency not reported: Inhibition of cortisol production (sometimes resulting in symptomatic adrenal insufficiency), adrenal crisis

Postmarketing reports: Adrenocortical insufficiency^[Ref]

Dermatologic

Frequency not reported: Erythema multiforme, rash, dermatitis, erythema, urticaria, pruritus, alopecia, xeroderma, dry skin, bruising, loss of scalp hair, worsening loss of scalp hair, desquamation

Postmarketing reports: Acute generalized exanthematous pustulosis, photosensitivity^[Ref]

Gastrointestinal

Common (1% to 10%): Gastrointestinal complaints (including nausea, vomiting)

Frequency not reported: Diarrhea, constipation, abdominal pain, upper abdominal pain, dry mouth, dysgeusia, dyspepsia, flatulence, tongue discoloration, stomatitis^[Ref]

Gastrointestinal intolerance may resolve with continued therapy and may improve if ketoconazole is taken with food.^[Ref]

Hematologic

Rare (less than 0.1%): Hemolytic anemia

Frequency not reported: Platelet count decreased, fatal aplastic anemia

Postmarketing reports: Thrombocytopenia^[Ref]

A 23-year-old female with vaginal discharge experienced fatal aplastic anemia coincident with ketoconazole therapy. She was admitted with widespread purpuric lesions on her face, arms, and legs. She had taken ketoconazole 200 mg twice daily for vaginal discharge for 4 days before admission. Ketoconazole was discontinued on admission. The patient was diagnosed with aplastic anemia based on clinical findings. The patient did not respond to therapy and died of disseminated candidiasis 2 months later.^[Ref]

Hypersensitivity

A 72-year-old female with a Candida albicans infection experienced a severe reaction of refractory anaphylactic shock coincident with ketoconazole therapy. She was initially given oral ketoconazole 200 mg twice daily. She developed hypotension over the first 2 days of treatment (BP 136/82 mmHg at baseline; 90/50 mmHg on day 2). Severe hypotension (BP 90/49 mmHg) unresponsive to fluid therapy or high-dose dopamine developed on day 4 of treatment. When laboratory tests revealed a high level of plasma tryptase, anaphylactic redistribution shock was diagnosed. Her vital signs became more stable after therapy with hydrocortisone and epinephrine infusion.^[Ref]

Frequency not reported: Anaphylactoid reaction, hypersensitivity reactions (including urticaria), anaphylaxis (sometimes after first dose), cross-sensitivity between imidazoles, drug hypersensitivity (presenting as rash, erythema, pruritus)

Postmarketing reports: Allergic conditions including anaphylactic shock, anaphylactic reaction, angioneurotic edema^[Ref]

Genitourinary

Gynecomastia and breast tenderness have been reported in male patients. Gynecomastia in males resulted from decreased steroidogenesis and testosterone production, which led to an increased estrogen to testosterone ratio.^[Ref]

Frequency not reported: Menstrual disorder, serum testosterone decreased, gynecomastia (in males), breast tenderness (in males), oligospermia, polymenorrhea anovulatory cycles, anovulatory oligomenorrhea

Postmarketing reports: Erectile dysfunction, azoospermia (with doses higher than recommended dose of 200 to 400 mg per day)^[Ref]

Metabolic

Rare (less than 0.1%): Hypoglycemia

Frequency not reported: Alcohol intolerance, anorexia, hyperlipidemia, increased appetite, transient fall in serum cholesterol with an increase in triglycerides^[Ref]

Nervous system

Frequency not reported: Headache, somnolence, dizziness, paresthesia

Postmarketing reports: Reversible increased intracranial pressure (e.g., papilledema, fontanel bulging in infants)^[Ref]

Other

Frequency not reported: Fatigue, asthenia, hot flush, malaise, peripheral edema, pyrexia, chills^[Ref]

Musculoskeletal

Frequency not reported: Myalgia

Postmarketing reports: Arthralgia^[Ref]

Psychiatric

Paranoid delusions have been reported in a patient treated with ketoconazole for cutaneous leishmaniasis.^[Ref]

Rare (less than 0.1%): Confusion, suicidal tendencies

Frequency not reported: Insomnia, nervousness, paranoid delusions^[Ref]

Ocular

Frequency not reported: Photophobia^[Ref]

Respiratory

Frequency not reported: Epistaxis^[Ref]