Names and pronunciation
(poe′sa-kon′a-zole) Noxafil, Posanol
PDF page 1063
Loading InternPractice…
Drug reference
(poe′sa-kon′a-zole) Noxafil, Posanol
PDF page 1063
Func. class.: Antifungal—systemic
PDF page 1063
Chem. class.: Triazole derivative
PDF page 1063
ACTION: Inhibits a portion of cell- wall synthesis; alters cell membranes and inhibits several fungal enzymes
PDF page 1063
USES: Prevention of aspergillus, can- dida infection, oropharyngeal candidiasis in immunocompromised patients, che- motherapy-induced neutropenia, muco- cutaneous candidiasis
PDF page 1063
Unlabeled uses: Aspergillosis, cellu- litis, coccidioidomycosis, endocarditis, endophthalmitis, esophageal candidia- sis, febrile neutropenia, fungal kerati- tis, fusariosis, histoplasmosis, infec- tious arthritis, myocarditis, osteomyelitis, pericarditis, sinusitis, tracheobronchitis
PDF page 1064
CONTRAINDICATIONS: Hyper sensitivity to this product or other systemic antifungals or azoles; fungal meningitis, onychomycosis or dermatomycosis in cardiac dysfunction; use with ergots, sirolimus, CYP3A4 substrates Precautions: Pregnancy, breastfeeding, children, cardiac/hepatic/renal disease
PDF page 1064
SIDE EFFECTS CNS: Headache, dizziness, insomnia, fever, rigors, weakness, anxiety CV: Hypo/hypertension, tachycardia, ane- mia, QT prolongation, torsades de pointes GI: Nausea, vomiting, anorexia, diar rhea, cramps, abdominal pain, flatu- lence, GI bleeding, hepatotoxicity GU: Gynecomastia, impotence, decreased libido INTEG: Pruritus, fever, rash, toxic epi- dermal necrolysis MISC: Edema, fatigue, malaise, hypokale- mia, tinnitus, rhabdomyolysis, hypokalemia
PDF page 1064
INTERACTIONS • Do not use with lovastatin, atorvastatin • Increase: QT prolongation—class IA/III antidysrhythmics, some phenothiazines, β agonists, local anesthetics, tricyclics, haloperidol, chloroquine, droperidol, pen- tamidine; CYP3A4 inhibitors (amiodarone, clarithromycin, erythromycin, telithro- mycin, troleandomycin), arsenic trioxide; CYP3A4 substrates (methadone, pimo zide, QUEtiapine, quiNIDine, risperiDONE, ziprasidone) Increase: tinnitus, hearing loss—qui NIDine Increase: hepatotoxicity—other hepato- toxic products Increase: severe hypoglycemia—oral hypoglycemics Increase: sedation—triazolam, oral mid- azolam Increase: levels, toxicity—busPIRone, busulfan, calcium-channel blockers, cla rithromycin, cycloSPORINE, diazePAM, digoxin, felodipine, HMG-CoA reductase inhibitors, indinavir, isradipine, midazolam, niCARdipine, NIFEdipine, niMODipine, phe- nytoin, quiNIDine, ritonavir, saquinavir, sirolimus, tacrolimus, vinca alkaloids, warfarin Decrease: posaconazole level—cimeti- dine, phenytoin Decrease: posaconazole action—antac- ids, H2-receptor antagonists, rifamycin, didanosine Drug/Food • Food increases absorption
PDF pages 1064, 1065
DOSAGE AND ROUTES Tablets and oral suspension are not in- terchangeable for dosing Invasive aspergillosis Adult/adolescent: PO DELAYED RE LEASE /IV 300 mg twice daily for 1 day, then 300 mg once daily × at least 6 to 12 wk Oropharyngeal candidiasis Adult: PO (oral suspension) 100 mg bid × 1 day, then 100 mg/day × 13 days
PDF page 1064
Available forms: Oral susp 200 mg/5 mL; del rel tab 100 mg; sol for inj 300 mg/16.7 mL
PDF page 1064
Administer: Delayed-release tab: do not divide, chew, crush; give with food IV route Intermittent IV INFUSION route • Dilution: bring to room temperature; transfer 16.7 mL of posaconazole to IV solution that is sufficient for final concen- tration of 1-2 mg/mL; use immediately • Store divided solution up to 24 hr re- frigerated • Use 0.22-micron PES or PVDF filter; give slowly over 90 min through central line; if central line is unavailable, may give a single dose through a peripheral line over 30 min; do not give multiple doses by this method PO route Oral susp: shake well; use calibrated mea- suring device; take only with full meal or liquid nutritional supplements such as En- sure; rinse measuring device after each use • Store in tight container in refrigerator; do not freeze
PDF page 1064
Assess: • Infection: type of, may begin treatment before obtaining results; temperature, WBC, sputum at baseline and periodically, breakthrough infections may occur when used with fosamprenavir • Fluid balance: I&O ratio, electrolytes; correct electrolyte imbalances before starting treatment • For allergic reaction: rash, photosensi- tivity, urticaria, dermatitis • Rhabdomyolysis: muscle pain, in- creased CPK; weakness, swelling of affected muscles; if these occur and if confirmed by CPK, product should be dis- continued • Hepatotoxicity: nausea, vomiting, jaundice, clay-colored stools, fatigue; he- patic studies (ALT, AST, bilirubin) if patient receiving long-term therapy • QT prolongation: ECG for QT prolonga- tion, ejection fraction; assess for chest pain, palpitations, dyspnea • Pregnancy/breastfeeding: use only if benefits outweigh fetal risk, may cause malformations; use in breastfeeding is not recommended
PDF page 1065
Evaluate: • Therapeutic response: decreased symptoms of fungal infection, negative C&S for infecting organism
PDF page 1065
CLINICAL CONSIDERATIONS
PDF page 1065
Patient and caregiver information: • That long-term therapy may be needed to clear infection (1 wk-6 mo, depending on infection) • To avoid hazardous activities if dizzi- ness occurs • To take 2 hr before administration of other products that increase gastric pH (antacids, H2 blockers, omeprazole, su- cralfate, anticholinergics); to notify health care provider of all medications taken (many interactions) • About the importance of compliance with product regimen; to use alternative method of contraception • To notify prescriber of GI symptoms, signs of hepatic dysfunction (fatigue, nau- sea, anorexia, vomiting, dark urine, pale stools) • To take during or within 20 min of eating
PDF page 1065
PHARMACOKINETICS Well absorbed, enhanced by food, pro- tein binding 98%-99%, peak 3-5 hr, half- life 35 hr, metabolized in liver, excreted in feces (77% unchanged)
PDF page 1064