Posanox100 mg

Established / FDA-Approved Uses

• Prophylaxis of invasive Aspergillus and Candida infections in patients at high risk due to being severely immunocompromised, including hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) and patients with hematologic malignancies who have prolonged chemotherapy-induced neutropenia. Approved for adults and pediatric patients 13 years and older (oral delayed-release tablet and oral suspension); the intravenous (IV) injection is approved for this use down to 2 years of age.
• Treatment of invasive aspergillosis in adults and pediatric patients 13 years and older (IV injection formulation), typically in patients who are refractory to or intolerant of other antifungal therapy.
• Treatment of oropharyngeal candidiasis (OPC), including OPC that is refractory to itraconazole and/or fluconazole, in adults and pediatric patients 13 years and older (oral suspension formulation).

Guideline-Supported / Adjunct Uses

• Used as part of combination or salvage antifungal therapy for selected invasive fungal infections (e.g., mucormycosis) refractory to or in patients intolerant of first-line agents, based on treatment guidelines rather than a specific FDA-labeled indication for this use.

Note: Posanox is a broad-spectrum antifungal reserved for confirmed or high-risk invasive fungal disease and prophylaxis in defined high-risk immunocompromised populations; it is not intended for routine or minor fungal infections.

Each Posaconazole delayed-release tablet contains 100 mg of Posaconazole. Posaconazole oral suspension contains 40 mg/mL of Posaconazole. Posaconazole injection contains 300 mg of Posaconazole per 16.7 mL (18 mg/mL) single-dose vial for intravenous infusion.

Posanox is a second-generation triazole antifungal medicine used for the prevention and treatment of serious, invasive fungal infections caused by organisms such as Aspergillus and Candida species, primarily in patients whose immune systems are severely weakened.

Posanox is available in three formulations — an oral delayed-release tablet, an oral suspension, and an intravenous injection — which have different absorption and bioavailability profiles and are not interchangeable at the same dose. The formulation, dose, and schedule must be selected and monitored by a physician based on the specific indication.

Triazole (azole) antifungal agent — Posanox belongs to the same broad drug class as fluconazole, itraconazole, and voriconazole, but has an extended spectrum of activity.

Pharmacokinetics

Posaconazole absorption and bioavailability differ by formulation. The oral suspension is absorbed better when taken with food or a liquid nutritional supplement and its absorption can be reduced by drugs that increase gastric pH or motility. The delayed-release tablet is not significantly affected by gastric pH or motility and generally produces higher, more consistent plasma concentrations than the oral suspension. The IV formulation achieves predictable systemic exposure independent of gastrointestinal absorption. Posaconazole is highly protein-bound, is metabolized mainly via glucuronidation (not extensively by CYP450 oxidative pathways), and is eliminated primarily in feces, with a long elimination half-life supporting once-daily maintenance dosing after an initial loading phase.

See Mode of Action for how Posaconazole exerts its antifungal effect.

Posanox formulations are administered differently and are not interchangeable:

• Delayed-release tablet: Swallow whole; do not crush, split, or chew. May be taken with or without food.
• Oral suspension: Shake well; take with a full meal or a liquid nutritional supplement to ensure adequate absorption. Use the provided measuring device.
• IV injection: For administration by a healthcare professional only, as a slow infusion over about 90 minutes through a central venous line with an in-line filter; never as a rapid IV push/bolus.

Always take or receive Posanox at the same times each day as prescribed, and complete the full course even if symptoms improve.

Posanox is a strong inhibitor of the CYP3A4 enzyme, so it significantly raises blood levels of many drugs metabolized by this pathway. Only well-established, clinically significant interactions are listed here; contraindicated combinations are listed separately under Contraindications.

Interactions Requiring Dose Adjustment or Close Monitoring

• Tacrolimus: Levels increase substantially; reduce tacrolimus dose to approximately one-third of the original and monitor trough levels closely.
• Cyclosporine: Levels increase; reduce cyclosporine dose to approximately three-fourths of the original and monitor trough levels.
• Midazolam and other sedating benzodiazepines metabolized by CYP3A4: Plasma levels can rise around five-fold, increasing sedation risk; use with caution and have reversal agents available if needed.
• Vinca alkaloids (vincristine, vinblastine): Increased risk of neurotoxicity, seizures, and other serious reactions; co-administration should be reserved for patients with no alternative antifungal options.
• Calcium channel blockers (e.g., verapamil, diltiazem, nifedipine): Increased levels; monitor for toxicity and reduce dose if needed.
• Digoxin: Plasma concentrations may rise; monitor digoxin levels.
• Rifabutin, phenytoin, efavirenz: These reduce Posanox concentrations substantially (by roughly 50%) and may increase their own levels; avoid combined use unless the benefit clearly outweighs the risk, with close monitoring.

QT-Prolonging Drugs

Avoid combining Posanox with other drugs known to prolong the QT interval where possible, due to an increased risk of dangerous heart rhythm disturbances (see Precautions and Warnings).

Drugs to Avoid Entirely

Certain drugs must never be combined with Posanox; see Contraindications for the complete list.

Common Side Effects

• Diarrhea, nausea, vomiting, abdominal pain, constipation
• Fever
• Headache
• Rash
• Peripheral edema, cough
• Low potassium (hypokalemia) or low magnesium (hypomagnesemia)
• Anemia, low platelet count (thrombocytopenia)

Serious Side Effects (Seek Medical Attention)

• Signs of liver problems: yellowing of skin/eyes, dark urine, severe fatigue, right upper abdominal pain (see Precautions and Warnings for hepatotoxicity monitoring).
• Irregular heartbeat, palpitations, or fainting, which may indicate QT prolongation or torsades de pointes.
• Signs of a severe allergic reaction: swelling of the face/throat, difficulty breathing, severe rash.
• Unusually high blood pressure with low potassium (pseudoaldosteronism), reported rarely.

Pregnancy

Animal studies have shown that Posanox may cause fetal harm (including skeletal malformations and pregnancy loss) at doses relevant to human exposure. Posanox should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus. Always consult a physician before use in pregnancy or if pregnancy occurs during treatment.

Breastfeeding

It is not known whether Posanox passes into human breast milk or what effect it may have on a breastfed infant. Because Posanox is excreted in the milk of lactating animals, a decision should be made, in consultation with a physician, whether to discontinue breastfeeding or discontinue the medicine, weighing the benefits of breastfeeding against the mother's need for treatment.

QT Prolongation

Posanox, like other azole antifungals, has been associated with prolongation of the QT interval on ECG and rare cases of torsades de pointes, a potentially life-threatening heart rhythm disturbance. Use with caution in patients with pre-existing heart rhythm disorders, and avoid combining with other QT-prolonging drugs where possible. Correct low potassium, magnesium, or calcium before and during treatment.

Liver Toxicity

Mild-to-moderate elevations in liver enzymes are common; rare cases of severe hepatic reactions, including cholestasis and liver failure (some fatal), have been reported, more often at higher doses. Liver function tests should be checked before starting and periodically during treatment, and Posanox should be discontinued if signs of liver disease develop.

Breakthrough Fungal Infections

Patients with severe diarrhea or vomiting should be monitored closely, since reduced drug absorption may increase the risk of breakthrough fungal infection.

Renal Considerations (IV Formulation)

The IV injection vehicle can accumulate in patients with moderate-to-severe kidney impairment; it should generally be avoided in this setting, with kidney function monitored and a switch to oral therapy considered if needed.

Antifungal Stewardship

Take Posanox exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice.

Formulations Are Not Interchangeable

Do not switch between Posanox tablet, suspension, and injection formulations without physician guidance, as they are dosed differently and are not bioequivalent.

Clinical experience with Posanox overdose is limited, and no specific antidote is available. Posanox is not effectively removed by hemodialysis. If an overdose of Posanox is suspected, seek immediate medical attention or contact a poison control center right away. Treatment is supportive, with monitoring of vital signs, heart rhythm (ECG), and liver function as directed by a physician; do not attempt specific home treatment for a suspected overdose.

Store the delayed-release tablet and oral suspension at room temperature (below 30°C), away from light and moisture; do not refrigerate or freeze the oral suspension. Store the injection as directed on the pack, protected from freezing, and use promptly once prepared for infusion, per healthcare provider instructions. Keep all forms out of reach of children.

• Renal impairment: No dose adjustment needed for oral Posanox; the IV formulation should generally be avoided if eGFR <50 mL/min (see Precautions and Warnings).
• Hepatic impairment: No initial dose adjustment established as necessary, but liver function should be monitored closely throughout treatment.
• Elderly patients: No overall differences in safety or effectiveness have been observed compared with younger adults; use with the same caution regarding kidney, liver, and heart rhythm monitoring.
• Body weight >120 kg: May have lower plasma concentrations of Posanox; closer clinical monitoring is advised.
• Pediatric patients: See Pediatric Uses.

Duration of Posanox therapy depends on the indication and clinical response:

• Prophylaxis of invasive fungal infections: Continued until recovery from neutropenia or immunosuppression, as determined by the treating physician.
• Oropharyngeal candidiasis: A total of 14 days of oral suspension therapy (1 day loading plus 13 days maintenance); refractory disease is treated based on severity and response.
• Invasive aspergillosis (IV): Typically 6 to 12 weeks, depending on the severity of the underlying disease, recovery from immunosuppression, and clinical/mycological response.

Do not stop Posanox early even if symptoms improve, unless advised by your physician, to reduce the risk of relapse or resistance.

Antifungals → Azole antifungals → Triazole antifungals (second-generation) — same broad class as fluconazole, itraconazole, and voriconazole, with Posaconazole used for its extended spectrum of activity.

Posaconazole works by inhibiting the fungal enzyme lanosterol 14-alpha-demethylase (a cytochrome P450-dependent enzyme), which is required to convert lanosterol to ergosterol. Ergosterol is an essential component of the fungal cell membrane. By blocking its synthesis, Posaconazole disrupts fungal cell membrane structure and function, leading to inhibition of fungal growth (fungistatic) and, for some organisms, fungal cell death (fungicidal). Posaconazole has a broader spectrum of activity than earlier azoles, covering many Aspergillus, Candida, and other mold species. See Pharmacology for absorption and elimination details.

Use of Posanox in children depends on the formulation and indication:

• Oral delayed-release tablet and oral suspension: Approved for prophylaxis of invasive Aspergillus and Candida infections, and (suspension only) for oropharyngeal candidiasis, in patients 13 years of age and older, using the same doses as adults.
• IV injection: Approved for prophylaxis in patients 2 years of age and older, with weight-based dosing (6 mg/kg, maximum 300 mg per dose) for those weighing 40 kg or less.
• Safety and efficacy have not been established in children younger than 2 years for the IV formulation, or younger than 13 years for the oral formulations.

Pediatric patients should be monitored for the same adverse effects as adults, including liver function and heart rhythm, as clinically indicated.