Summary

Commonly reported side effects of posaconazole include: cytomegalovirus disease, febrile neutropenia, herpes simplex infection, abdominal pain, anemia, arthralgia, back pain, constipation, cough, diarrhea, dizziness, dyspepsia, epistaxis, fatigue, fever, headache, hyperbilirubinemia, hyperglycemia, hypertension, hypokalemia, hypotension, insomnia, lower extremity edema, mucositis, musculoskeletal pain, nausea, neutropenia, petechia, pharyngitis, pruritus, rigors, skin rash, tachycardia, thrombocytopenia, vaginal hemorrhage, vomiting, anorexia, and bacteremia. Other side effects include: upper respiratory tract infection, anxiety, asthenia, edema, hypocalcemia, and prolonged qt interval on ecg. Continue reading for a comprehensive list of adverse effects.

Applies to posaconazole: oral powder for suspension extended release, oral suspension, oral tablet delayed release. Other dosage forms:

• intravenous solution

Serious side effects of Posaconazole

Along with its needed effects, posaconazole 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 posaconazole:

More common

• Black, tarry stools
• bleeding in the gums
• blood in the urine or stools
• bloody nose
• blurred vision
• body aches or pain
• chest tightness
• confusion
• cough
• decreased urine
• diarrhea
• difficult or labored breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• dry mouth
• fever or chills
• fruit-like breath odor
• heavy non-menstrual vaginal bleeding
• increased thirst or urination
• irregular heartbeats
• loss of appetite
• loss of voice
• mood changes
• muscle pain, cramps, spasms, or twitching
• nausea or vomiting
• numbness or tingling in the hands, feet, lips, mouth, or fingertips
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• seizures
• slow or fast heartbeat
• small red or purple spots on the skin
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• stomach pain
• sweating
• swelling of the ankles or hands
• tender, swollen glands in the neck
• trembling
• trouble swallowing
• unexplained weight loss
• unusual bleeding or bruising
• yellow eyes or skin

Less common

• Fainting
• irregular heartbeat, recurrent

Incidence not known

• Anxiety
• change in mental status
• chest pain or discomfort
• darkening of the skin
• itching or skin rash
• mental depression
• seizures
• swelling of the eyes or eyelids
• swelling of the face, fingers, feet, or lower legs
• trouble breathing
• weakness

Other side effects of Posaconazole

Some side effects of posaconazole 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 having a bowel movement (stool)
• heartburn
• lack or loss of strength
• muscle stiffness
• pain in the joints
• trouble sleeping

Less common

• Bad, unusual, or unpleasant (after) taste
• change in taste

For Healthcare Professionals

Applies to posaconazole: intravenous solution, oral delayed release tablet, oral powder for reconstitution delayed release, oral suspension.

General

Thrombophlebitis was very common when multiple doses of the injection were administered via peripheral venous catheter, leading to administration via central venous catheter in later studies. The most common side effects reported with the IV injection were diarrhea, hypokalemia, pyrexia, and nausea.

The most common side effects reported with the delayed-release tablets were diarrhea, pyrexia, and nausea. The most common side effect leading to discontinuation of the delayed-release tablets was nausea (2%).

In the clinical trial of the injection and delayed-release tablet for treatment of invasive aspergillosis, the most common side effects leading to discontinuation of therapy included septic shock, respiratory failure, and bronchopulmonary aspergillosis.

The most common side effects reported with the oral suspension in the prophylaxis clinical trials were fever, diarrhea, and nausea. The most common side effects leading to discontinuation of the oral suspension in these trials were associated with gastrointestinal disorders, including nausea (2%), vomiting (2%), and increased liver enzymes (2%).

The most common side effects reported with the oral suspension in the oropharyngeal candidiasis and refractory oropharyngeal candidiasis trials were fever, diarrhea, nausea, headache, vomiting, and coughing. The most common side effects leading to discontinuation of the oral suspension were respiratory impairment (1%) and pneumonia (1%) in patients with oropharyngeal candidiasis and AIDS (7%) and respiratory impairment (3%) in patients with refractory oropharyngeal candidiasis. Side effects occurred more often in patients with refractory oropharyngeal candidiasis. Serious side effects were reported in 55% of highly immunocompromised patients with advanced HIV disease. Fever (13%) and neutropenia (10%) were the serious side effects reported most often in these patients. Other serious side effects included altered drug levels (of other products), increased hepatic enzymes, nausea, rash, vomiting, bilirubinemia, and hepatocellular damage.^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 42%), nausea (up to 38%), vomiting (up to 29%), abdominal pain (up to 27%), constipation (up to 21%), oral candidiasis (up to 12%), upper abdominal pain (up to 11%)

Common (1% to 10%): Dyspepsia, dry mouth, flatulence, anorectal discomfort

Uncommon (0.1% to 1%): Mucositis, taste perversion, pancreatitis, mouth ulceration, loose stools, abdominal distension, dysphagia, ascites, eructation, gastritis, gastroesophageal reflux disease, esophagitis, tongue edema, tongue discoloration, tooth discoloration, mouth edema, enteritis, epigastric discomfort

Rare (0.01% to 0.1%): Gastrointestinal hemorrhage, ileus, esophageal candidiasis, increased amylase, increased lipase, abdominal tenderness, cheilitis, hemorrhagic diarrhea, esophageal ulceration, hemorrhagic gastritis, odynophagia, increased pancreatic enzymes, proctalgia, retching, aphthous stomatitis, tenesmus, melena, gingivitis, glossitis, stomatitis^[Ref]

Other

Alkaline phosphatase greater than 3 times the upper limit of normal (3 x ULN) was reported in up to 14% of patients.^[Ref]

Very common (10% or more): Fever/pyrexia (up to 45%), rigors (up to 20%), fatigue (up to 17%), peripheral edema (up to 16%), chills (up to 16%), leg edema (up to 15%), increased alkaline phosphatase (up to 14%), mucosal inflammation (up to 14%), asthenia (up to 13%), herpes simplex (up to 11%), pain (up to 11%)

Common (1% to 10%): Edema, weakness, changes in alkaline phosphatase, catheter site erythema

Uncommon (0.1% to 1%): Altered drug levels, malaise, chest pain, flushing, hot flushes, thirst, drug toxicity, chest discomfort, drug intolerance, feeling jittery, decreased blood phosphorus

Rare (0.01% to 0.1%): Face edema, catheter-related infection, non-herpetic cold sores

Frequency not reported: Bacteremia, cytomegalovirus infection, septic shock^[Ref]

Metabolic

Very common (10% or more): Hypokalemia (up to 30%), anorexia (up to 19%), hypomagnesemia (up to 18%), decreased weight (up to 14%), decreased appetite (up to 12%), hyperglycemia (up to 11%), dehydration (up to 11%)

Common (1% to 10%): Hypocalcemia, electrolyte imbalance

Uncommon (0.1% to 1%): Hypertriglyceridemia, hyperuricemia, increased LDH, hypoglycemia

Rare (0.01% to 0.1%): Hypercholesterolemia, hyperlipemia, hyperproteinemia, hypoalbuminemia, metabolic acidosis, vitamin K deficiency, increased weight^[Ref]

Hematologic

Very common (10% or more): Thrombocytopenia (up to 29%), anemia (up to 25%), neutropenia (up to 23%), febrile neutropenia (up to 20%)

Uncommon (0.1% to 1%): Leukopenia, eosinophilia, lymphadenopathy, splenic infarction

Rare (0.01% to 0.1%): Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, pancytopenia, coagulopathy/coagulation disorder, hemorrhage, abnormal blood gases, neutrophilia, increased platelet count, decreased prothrombin, prolonged prothrombin time, purpura

Frequency not reported: Aggravated neutropenia^[Ref]

Rare occurrences of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been reported, generally in patients with concurrent cyclosporine or tacrolimus therapy for the prevention of transplant rejection or graft versus host disease.^[Ref]

Nervous system

Very common (10% or more): Headache (up to 28%), dizziness (up to 11%)

Common (1% to 10%): Paresthesia, somnolence, dysgeusia

Uncommon (0.1% to 1%): Tremor, convulsions, neuropathy, hypoesthesia, earache, vertigo, aphasia

Rare (0.01% to 0.1%): Cerebrovascular accident, encephalopathy, peripheral neuropathy, syncope, hearing impairment, areflexia, ataxia, impaired cognition, dysphonia, dystonia, hemiparesis, hyperkinesia, hyperreflexia, hyporeflexia, hypotonia, impaired concentration, memory impairment, meningism, mononeuritis, restless leg syndrome, sciatica, tinnitus^[Ref]

Respiratory

Rare occurrences of pulmonary embolus have been reported, generally in patients with concurrent cyclosporine or tacrolimus therapy for the prevention of transplant rejection or graft versus host disease.^[Ref]

Very common (10% or more): Cough/coughing (up to 25%), dyspnea (up to 20%), epistaxis (up to 17%), pneumonia (up to 12.5%), pharyngitis (up to 12%)

Uncommon (0.1% to 1%): Sinusitis, nasal congestion, hiccups, pleuritic pain, tachypnea, abnormal chest x-ray

Rare (0.01% to 0.1%): Pulmonary hypertension, interstitial pneumonia, pneumonitis, upper respiratory tract infection, pulmonary embolism, atelectasis, dry throat, nasal irritation, postnasal drip, pulmonary infiltration, rales, rhinitis, rhinorrhea

Frequency not reported: Respiratory failure, bronchopulmonary aspergillosis^[Ref]

Dermatologic

Very common (10% or more): Rash (up to 24%), pruritus (up to 11%), petechiae (up to 11%)

Common (1% to 10%): Increased sweating

Uncommon (0.1% to 1%): Alopecia, dry skin, maculopapular rash, urticaria, furunculosis, acne, pruritic rash, dermatitis, erythema

Rare (0.01% to 0.1%): Stevens-Johnson syndrome, vesicular rash, erythematous rash, follicular rash, macular rash, night sweats, seborrhea, skin nodule, ecchymoses^[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 18%), hypotension (up to 14%), tachycardia (up to 12%)

Uncommon (0.1% to 1%): Long QT syndrome, abnormal ECG, palpitations, bradycardia, QT/QTc prolongation, atrial fibrillation, atrial flutter, bundle branch block, extrasystoles, ventricular hypertrophy, supraventricular extrasystoles, vasculitis, thrombophlebitis

Rare (0.01% to 0.1%): Torsades de pointes, deep vein thrombosis, sudden death, ventricular tachycardia, cardiorespiratory arrest, cardiac failure, myocardial infarction, aortic valve sclerosis, cardiomegaly, decreased ejection fraction, mitral valve disease, supraventricular tachycardia, premature atrial contractions, premature ventricular contractions, atrioventricular block, atherosclerosis, ischemia, hematoma^[Ref]

One patient taking this drug during a clinical trial developed torsades de pointes. This severely ill patient had a history of palpitations, recent cardiotoxic chemotherapy, hypokalemia, and hypomagnesemia; risk factors that may have contributed to or confounded the patient's condition.^[Ref]

Hepatic

Clinically significant liver test abnormalities during oropharyngeal candidiasis studies included increased AST, alkaline phosphatase, ALT, and total bilirubin. The majority of abnormal liver function tests in patients and healthy subjects were minor, transient, and did not lead to therapy discontinuation.

Changes in liver test results from grade 0, 1, or 2 at baseline to grade 3 or 4 during prophylaxis and aspergillosis treatment studies included changes in ALT, bilirubin, AST, and alkaline phosphatase.

Total bilirubin greater than 1.5 x ULN (up to 22%), AST greater than 3 x ULN (up to 17%), and ALT greater than 3 x ULN (up to 11%) were reported.^[Ref]

Very common (10% or more): Increased AST (up to 17%), changes in ALT (up to 17%), increased ALT (up to 14.6%)

Common (1% to 10%): Bilirubinemia, changes in bilirubin, increased total bilirubin, increased hepatic enzymes, changes in AST, increased GGT, raised liver function tests (increased ALT, increased AST, increased bilirubin, increased alkaline phosphatase, increased GGT)

Uncommon (0.1% to 1%): Hepatocellular damage, abnormal hepatic function, hepatitis, hepatomegaly, jaundice, cholestasis, hepatic toxicity

Rare (0.01% to 0.1%): Hepatic failure, cholestatic hepatitis, hepatosplenomegaly, liver tenderness, asterixis, splenomegaly

Postmarketing reports: Severe hepatic injury with fatal outcome^[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 17%)

Uncommon (0.1% to 1%): Altered mental status, anxiety, confusion/confusional state, abnormal dreams, sleep disorder

Rare (0.01% to 0.1%): Psychotic disorder, depression, amnesia, emotional lability, decreased libido, paroniria, psychosis, delirium^[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (up to 16%), arthralgia (up to 11%)

Common (1% to 10%): Back pain

Uncommon (0.1% to 1%): Myalgia, flank pain, muscle weakness, pain in extremity, neck pain

Rare (0.01% to 0.1%): Bone pain, chest wall pain, fasciitis, neck stiffness, cramps in the extremities, muscle cramps^[Ref]

Local

Very common (10% or more): Infusion site reactions (up to 12%)

Uncommon (0.1% to 1%): Infusion site pain, infusion site phlebitis, infusion site thrombosis

In initial studies of healthy subjects, use of a single dose of this drug infused over 30 minutes via a peripheral venous catheter was associated infusion site reactions (12%), including thrombophlebitis (4%). Incidence of thrombophlebitis increased to 60% when multiple doses were administered via a peripheral venous catheter; therefore, in subsequent studies, this drug was administered via central venous catheter. When a central venous catheter was not readily available, patients received a single infusion over 30 minutes via a peripheral venous catheter; peripheral infusion time longer than 30 minutes led to higher incidence of infusion site reactions and thrombophlebitis.

Genitourinary

Very common (10% or more): Vaginal hemorrhage (10%)

Uncommon (0.1% to 1%): Menstrual disorder, albuminuria, altered micturition frequency, dysuria, hematuria, nocturia

Rare (0.01% to 0.1%): Breast pain, urinary tract infection, micturition disorder, urinary tract obstruction, leukorrhea^[Ref]

Renal

Uncommon (0.1% to 1%): Acute renal failure, increased blood creatinine, renal failure, renal impairment

Rare (0.01% to 0.1%): Renal tubular acidosis, interstitial nephritis, increased BUN, renal calculus^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction

Rare (0.01% to 0.1%): Hypersensitivity reactions^[Ref]

Ocular

Uncommon (0.1% to 1%): Blurred vision, photophobia, conjunctivitis, reduced visual acuity

Rare (0.01% to 0.1%): Diplopia, scotoma, eye pain, dry eyes, periorbital edema^[Ref]

Endocrine

Rare (0.01% to 0.1%): Adrenal insufficiency, decreased blood gonadotropins

Postmarketing reports: Pseudoaldosteronism^[Ref]