Posaconazole

DEA Class; Rx

Common Brand Names; Noxafil

• Antifungals, Systemic; 

Oral and intravenous azole antifungal agent
Used for the treatment of invasive aspergillosis and oropharyngeal candidiasis and for prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients
Oral dose formulations not interchangeable due to differences in dosing

Hypersensitivity to posaconazole or other azoles

Coadministration with sirolimus; increases sirolimus blood concentrations by ~9-fold

CYP3A4 substrates that prolong the QT interval (eg, pimozide, quinidine)

Coadministration with the HMG-CoA reductase inhibitors (statins) that are primarily metabolized through CYP3A4 (eg, atorvastatin, lovastatin, simvastatin)

Concurrent use with ergot alkaloids

Coadministration with venetoclax in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

Use of delayed-release oral suspension in patients with known or suspected hereditary fructose intolerance (HFI)

Delayed-release oral suspension only

• Patients with known or suspected hereditary fructose intolerance (HFI)

Injection

• Diarrhea (10-42%)

• Pyrexia (21-31%)

• Nausea (19-30%)

• Hypokalemia (22-28%)

• Rash (15-24%)

• Headache (14-21%)

• Vomiting (12-19%)

• Epistaxis (14-17%)

• Abdominal pain (13-17%)

• Peripheral edema (12-15%)

• Cough (9-13%)

• Constipation (8-13%)

• Hypomagnesemia (11-13%)

• Decreased appetite (10-12%)

• Hypertension (8-11%)

• Thrombocytopenia (7-11%)

• Upper abdominal pain (6-11%)

Oral suspension

• Fever (6-45%)

• Nausea (9-38%)

• Hypokalemia (30%)

• Thrombocytopenia (29%)

• Vomiting (7-29%)

• Headache (8-28%)

• Abdominal pain (5-27%)

• Coughing (3-25%)

• Anemia (2-25%)

• Neutropenia (4-23%)

• Constipation (21%)

• Dyspnea (1-20%)

• Rigors (<20%)

• Anorexia (2-19%)

• Rash (3-19%)

• Hypomagnesemia (18%)

• Hypertension (18%)

• ALT increased, Grade 3 or 4 (6-17%)

• AST >3x ULN (6-17%)

• Fatigue (2-17%)

• Insomnia (1-17%)

• Musculoskeletal pain (16%)

• Edema legs (15%)

• Epistaxis (14%)

• Hypotension (14%)

• Decrease weight (1-14%)

• Tachycardia (12%)

• Pharyngitis (12%)

May prolong QT interval; cases of torsades de pointes reported

Hepatic reactions reported including mild-to-moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and clinical hepatitis; consider discontinuing therapy in patients who develop abnormal LFTs or monitor LFTs during treatment

Closely monitor patients with severe renal impairment for breakthrough fungal infections due to the variability in exposure of the delayed-release tablets and oral suspension; avoid use of injection in patients with moderate or severe renal impairment (eGFR <50 mL/min); unless benefit outweighs risks

Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy

Closely monitor patients who have severe diarrhea or vomiting for breakthrough fungal infections when receiving delayed-release tablets, oral suspension, or delayed-release oral suspension

Available data in pregnant women are insufficient to establish a drug- associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; based on findings from animal data, therapy may cause fetal harm when administered to pregnant women

There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production

Posaconazole

oral suspension

• 40mg/mL (105mL)

tablet, delayed-release

• 100mg

injectable solution

• 18mg/mL (300mg/16.7mL-vial)