Noxafil

Action

Inhibits fungal ergosterol synthesis (key component of fungal cell membrane) by inhibiting lanosterol 14-alpha demethylase and causing methylated sterol precursors to accumulate

Availability

Oral suspension (immediate-release): 40 mg/ml in 123-ml bottle

Indications and dosages

➣ Prophylaxis of invasive Aspergillus and Candida infections in patients at risk for these infections because of severe immunocompromise (such as hematopoietic stem-cell transplant recipients with graft-versus-host disease and those who have hematologic cancers with prolonged neutropenia from chemotherapy)

Adults and children age 13 and older: 200 mg (5 ml) P.O. three times daily for duration of therapy based on recovery from neutropenia or immunosuppression

➣ Oropharyngeal candidiasis

Adults and children age 13 and older: Loading dose of 100 mg (2.5 ml) P.O. twice daily on first day, then 100 mg P.O. once daily for 13 days

➣ Oropharyngeal candidiasis refractory to itraconazole or fluconazole

Adults and children age 13 and older: 400 mg (10 ml) P.O. twice daily for duration of therapy based on disease severity and clinical response

Off-label uses

• Esophageal candidiasis

• Fusarium infection

• Mycosis

Contraindications

• Hypersensitivity to drug or its components

• Concurrent use of astemizole, cisapride, ergot alkaloids, halofantrine, pimozide, quinidine, sirolimus, or terfenadine

Precautions

Use cautiously in:

• hypersensitivity to other azoles

• potentially proarrhythmic conditions, severe underlying medical conditions (such as hematologic cancers), preexisting hepatic impairment

• pregnant or breastfeeding patients

• children younger than age 13 (safety and efficacy not established).

Administration

• Before starting drug, make rigorous attempts to correct potassium, magnesium, and calcium imbalances.

• Advise patient to take each dose with full meal or liquid nutritional supplement to enhance drug absorption.

See Don't give concurrently with astemizole, cisapride, ergot alkaloids, halofantrine, pimozide, quinidine, or terfenadine.

Adverse reactions

CNS: seizure, insomnia, anxiety, headache, fatigue, dizziness, weakness

CV: prolonged QT interval, hypertension, hypotension, tachycardia

EENT: blurred vision, epistaxis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, mucositis, dry mouth, oral candidiasis, anorexia

GU: vaginal hemorrhage

Hematologic: anemia, neutropenia, febrile neutropenia, thrombocytopenia

Hepatic: cholestasis, hepatic damage, hepatic failure

Metabolic: adrenal insufficiency (rare), dehydration

Musculoskeletal: arthralgia, back pain

Respiratory: cough, dyspnea, upper respiratory tract infection, pneumonia

Skin: rash, pruritus, petechiae

Other: unusual taste, weight loss, fever, bacteremia, herpes simplex, edema, leg edema, rigors, cytomegalovirus infection

Interactions

Drug-drug. Astemizole, cisapride, halofantrine, pimozide, quinidine, terfenadine: elevated blood levels of these drugs, leading to prolonged QT interval and increased risk of life-threatening arrhythmias (including torsades de pointes)

Benzodiazepines metabolized through CYP3A4 (such as midazolam), pheny-toin, rifabutin: increased blood levels of these drugs

Calcium channel blockers metabolized through CYP3A4 (such as amlodipine, diltiazem, felodipine): increased blood levels of these drugs, causing increased toxicity risk

Cimetidine, phenytoin, rifabutin: decreased posaconazole blood level

Cyclosporine, sirolimus, tacrolimus: elevated blood levels of these drugs, causing increased risk of nephrotoxicity and other serious adverse reactions

Ergot derivatives (dihydroergotamine, ergotamine): increased blood levels of these drugs, causing increased ergotism risk

HMG-CoA reductase inhibitors metabolized through CYP3A4 (such as atorvas-tatin, fluvastatin, lovastatin): increased blood levels of these drugs, causing increased risk of rhabdomyolysis

Vinca alkaloids (such as vinblastine, vincristine): increased vinca alkaloid blood levels, causing increased neuro-toxicity risk

Drug-diagnostic tests. Alanine amino-transferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, gamma-glutamyltransferase, serum creatinine: increased levels

Drug-food. Nonfat, high-fat, or liquid nutritional supplements: approximately three-to four-fold increase in drug mean C_max and area under the curve values

Patient monitoring

• Monitor serum potassium, magnesium, and calcium levels before and frequently during therapy.

• Obtain liver function tests and bilirubin level at start of therapy and periodically throughout. If liver function tests become abnormal during therapy, stay alert for signs and symptoms of more severe hepatic injury; consider withdrawing drug if these occur.

• Monitor blood drug levels frequently if patient is receiving concurrent cyclosporine, sirolimus, or tacrolimus. Consider reducing dosage as appropriate.

See Monitor ECG if patient has potentially proarrhythmic condition or is receiving concurrent drugs that may prolong QT interval and are metabolized through CYP3A4. Stay alert for prolonged QT interval.

• Watch for breakthrough fungal infections in patients with severe diarrhea, vomiting, or severe renal impairment and in those receiving drugs that may decrease blood drug level or who can't eat a full meal or tolerate oral nutritional supplements.

Patient teaching

• Instruct patient to take each dose with full meal or liquid nutritional supplement.

• Advise patient to inform prescriber of all drugs he is taking because serious interactions may occur.

See Urge patient to contact prescriber immediately if he develops signs or symptoms of liver impairment, such as unusual tiredness, weakness, nausea, itching, yellowing of eyes or skin, upper right abdominal tenderness, or flulike symptoms.

See Tell patient to contact prescriber immediately if he develops irregular heartbeats or other cardiac symptoms.

See Advise patient to notify prescriber of severe diarrhea or vomiting, because these conditions may alter blood drug level.

• Stress importance of keeping appointments for follow-up laboratory tests.

• Caution patient to avoid driving and other hazardous activities because drug may alter vision.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and foods mentioned above.