Applies to levoketoconazole: oral tablet.
Warning
Oral route (Tablet)
HepatotoxicityCases of hepatotoxicity with a fatal outcome or requiring liver transplantation have been reported with the use of oral ketoconazole. Some patients had no obvious risk factors for liver disease. Serious hepatotoxicity has been reported in patients receiving levoketoconazole.Levoketoconazole is contraindicated in patients with cirrhosis, acute liver disease or poorly controlled chronic liver disease, recurrent symptomatic cholelithiasis, a prior history of drug induced liver injury to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease.Evaluate liver enzymes prior to and during treatment. Interrupt levoketoconazole treatment immediately if signs of hepatotoxicity occur.QT ProlongationLevoketoconazole is associated with dose-related QT interval prolongation. QT interval prolongation may lead to life-threatening ventricular dysrhythmias such as torsades de pointes.Coadministration of levoketoconazole with other drugs that prolong the QT interval associated with ventricular arrhythmias, including torsades de pointes, and use in patients with a prolonged QTcF interval of greater than 470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or long QT syndrome (including first-degree family history) are contraindicated.Perform an ECG and correct hypokalemia and hypomagnesemia prior to and during treatment. Temporarily discontinue levoketoconazole if QTcF interval exceeds 500 msec.
Serious side effects of Levoketoconazole
Along with its needed effects, levoketoconazole 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 levoketoconazole:
More common
- Bleeding gums
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- body aches or pain
- chills
- cough
- coughing up blood
- darkening of the skin
- decreased interest in sexual intercourse
- decreased urine
- diarrhea
- difficulty in swallowing
- dizziness
- dry mouth
- ear congestion
- fainting
- fever
- headache
- inability to have or keep an erection
- increased menstrual flow or vaginal bleeding
- increased thirst
- loss in sexual ability, desire, drive, or performance
- loss of appetite
- loss of voice
- mental depression
- mood changes
- muscle pain or cramps
- nausea or vomiting
- nervousness
- nosebleeds
- numbness or tingling in the hands, feet, or lips
- paralysis
- prolonged bleeding from cuts
- pounding in the ears
- rapid weight gain
- red or black, tarry stools
- red or dark brown urine
- seizures
- slow or fast heartbeat
- sneezing
- sore throat
- stuffy or runny nose
- trouble breathing
- unusual tiredness or weakness
- unusual weight gain or loss
Less common
- Swelling of the breasts or breast soreness in both females and males
Incidence not known
- Bulging soft spot on head of an infant
- change in ability to see colors, especially blue or yellow
- chest tightness
- dark urine
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- pinpoint red spots on skin
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- stomach pain, severe
- trouble sleeping
- unusual bleeding or bruising
- yellow eyes or skin
Other side effects of Levoketoconazole
Some side effects of levoketoconazole 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:
More common
- Acid or sour stomach
- back pain
- belching
- difficulty in moving
- heartburn
- indigestion
- loss or thinning of the hair
- muscle aches or stiffness
- pain, swelling, or redness in the joints
- stomach discomfort or upset
Incidence not known
- Increased sensitivity of the skin to sunlight
- redness or other discoloration of the skin
- severe sunburn
For Healthcare Professionals
Applies to levoketoconazole: oral tablet.
General
The most significant adverse reactions were hepatotoxicity, QT prolongation, and hypocortisolism.[Ref]
Hepatic
Level 2
Up to 27% of the patients had at least 1 liver-related adverse reaction.
Percentage of patients with elevations in AST or ALT:
-AST or ALT greater than the upper limit of normal (ULN): 45%
-AST or ALT greater than 3 times ULN (3 x ULN): 11%
-AST or ALT greater than 5 x ULN: 5%
-AST or ALT greater than 10 x ULN: 3%[Ref]
Very common (10% or more): Liver enzyme elevation (included elevated AST, elevated ALT, elevated alkaline phosphatase, elevated GGT; 20%)
Common (1% to 10%): Hepatic pain, drug-induced liver injury, liver disorders
Uncommon (0.1% to 1%): Hepatic steatosis
Ketoconazole:
-Postmarketing reports: Serious hepatotoxicity including hepatitis cholestatic, biopsy-confirmed hepatic necrosis, cirrhosis, hepatic failure including cases resulting in transplantation or death[Ref]
Cardiovascular
Very common (10% or more): Hypertension (up to 24%), arrythmia (included ECG QT prolonged, ECG T wave abnormal, palpitations, sinus tachycardia, paroxysmal tachycardia, ventricular extrasystoles, bradycardia, carotid pulse increased, defect conduction intraventricular, heart rate increased, sinus bradycardia; up to 24%)
Frequency not reported: QTc interval prolongation[Ref]
Level 2
In general, 2.4% of the patients experienced QTcF greater than 500 msec, while 14.7% of patients experienced change-from-baseline QTcF greater than 60 msec.[Ref]
Endocrine
Very common (10% or more): Adrenal insufficiency (10%)
Common (1% to 10%): Hypocortisolism, gynecomastia, hypogonadism
Ketoconazole:
-Postmarketing reports: Adrenocortical insufficiency[Ref]
Dermatologic
Very common (10% or more): Erythema (included flushing; 43%), rash (17%), pruritus (15%), dry skin (up to 12%), alopecia (up to 11%)
Ketoconazole:
-Postmarketing reports: Acute generalized exanthematous pustulosis, photosensitivity[Ref]
Other
Very common (10% or more): Fatigue (up to 39%), peripheral edema (20%)[Ref]
Nervous system
Very common (10% or more): Headache (up to 38%), presyncope/syncope (18%) dizziness (15%), disturbance in attention (14%)
Ketoconazole:
-Postmarketing reports: Reversible intracranial pressure increased (e.g., papilledema, fontanelle bulging in infants)[Ref]
Gastrointestinal
Very common (10% or more): Nausea/vomiting (up to 37%), abdominal pain/dyspepsia (included abdominal pain, abdominal distension, dyspepsia, gastric disorder, abdominal discomfort, gastritis, other related terms; up to 33%), diarrhea (up to 19%), dry mouth (11%)
Common (1% to 10%): Gastrointestinal infection[Ref]
Metabolic
Very common (10% or more): Hypokalemia (up to 29%), decreased appetite (13%)[Ref]
Musculoskeletal
Very common (10% or more): Arthritis (28%), myalgia (26%), back pain (22%)[Ref]
Genitourinary
Very common (10% or more): Abnormal uterine bleeding (up to 24%), urinary tract infection (up to 16%)
Ketoconazole:
-Postmarketing reports: Erectile dysfunction, azoospermia[Ref]
Level 2
Azoospermia was reported with dosages higher than 200 or 400 mg daily.[Ref]
Psychiatric
Very common (10% or more): Insomnia/sleep disturbances (22%), irritability (14%), depression (12%)
Common (1% to 10%): Decreased libido[Ref]
Respiratory
Very common (10% or more): Upper respiratory infection (up to 28%)
Hypersensitivity
Uncommon (0.1% to 1%): Hypersensitivity
Ketoconazole:
-Postmarketing reports: Allergic conditions including anaphylactic shock, anaphylactic reaction, angioneurotic edema[Ref]
Hematologic
Very common (10% or more): Hemorrhage/contusion (included blood urine present, epistaxis, eye hemorrhage, gingival bleeding, hematoma, hematuria, hemorrhoidal hemorrhage, melena, scleral hemorrhage, conjunctival hemorrhage, ecchymosis, hyphema, RBCs urine; up to 40%),
Ketoconazole:
-Postmarketing reports: Thrombocytopenia[Ref]
