Tericin50 mg/vial

Tericin is a polyene antifungal used for the treatment of serious, systemic, and often life-threatening fungal infections. Its use is generally reserved for confirmed or strongly suspected invasive fungal disease, under specialist (infectious disease) supervision.

Established / guideline-supported uses (intravenous formulations)

• Invasive candidiasis (including candidemia), especially when azole resistance is suspected or in critically ill patients
• Invasive aspergillosis, particularly as alternative therapy when first-line azole therapy (e.g., voriconazole) is not tolerated or has failed
• Cryptococcal meningitis (typically used in combination with flucytosine as induction therapy)
• Histoplasmosis, blastomycosis, and coccidioidomycosis (moderate-to-severe or disseminated disease)
• Mucormycosis (first-line therapy for this typically resistant mould infection)
• Visceral leishmaniasis (liposomal formulation specifically indicated for this)
• Empirical antifungal therapy in persistently febrile, neutropenic patients when no other cause of fever is found

Localized / non-systemic uses (topical and oral non-absorbed formulations)

• Cutaneous and mucocutaneous candidiasis (topical preparations)
• Oral/gastrointestinal candidiasis limited to the gut lumen (non-absorbed oral suspension, where available)

Note: Tericin is not used for minor, localized, or non-life-threatening fungal infections when safer, better-tolerated alternatives (e.g., azoles, echinocandins) are suitable.

Each vial contains Amphotericin B as the active pharmaceutical ingredient, formulated either as:

• Conventional Amphotericin B deoxycholate powder for injection (with sodium desoxycholate and buffer), or
• A lipid-based formulation — liposomal Amphotericin B, Amphotericin B lipid complex, or Amphotericin B colloidal dispersion — designed to reduce toxicity while maintaining antifungal activity

Topical formulations (cream, lotion, ointment) contain Amphotericin B in a non-absorbed base for local application. Exact excipients vary by manufacturer and formulation.

Tericin is a naturally occurring polyene macrolide antifungal antibiotic derived from Streptomyces nodosus. It has broad-spectrum fungicidal/fungistatic activity against many clinically important yeasts and moulds and has been a mainstay of therapy for severe systemic mycoses for decades.

Because the conventional (deoxycholate) formulation is associated with significant infusion-related and renal toxicity, lipid-based formulations were developed to improve tolerability while retaining efficacy. Tericin is administered intravenously for systemic infections under close medical supervision, and is also available in topical/non-absorbed oral forms for localized disease.

Polyene Antifungal Antibiotic (Tericin and its lipid-based formulations)

Mechanism of action

Amphotericin B binds preferentially to ergosterol, the main sterol in the fungal cell membrane. This binding forms transmembrane pores/channels that increase membrane permeability, causing leakage of intracellular potassium and other essential cellular contents, ultimately leading to fungal cell death (fungicidal at higher concentrations, fungistatic at lower concentrations depending on organism and susceptibility).

Selectivity and toxicity basis

Amphotericin B has a much higher affinity for ergosterol than for cholesterol (the analogous sterol in human cell membranes), which underlies its antifungal selectivity. However, some binding to human cholesterol still occurs, which is believed to be the basis for many of its dose-limiting toxicities, particularly nephrotoxicity and infusion-related reactions.

Pharmacokinetics

Amphotericin B is poorly absorbed orally and must be given intravenously for systemic effect. It is highly protein-bound, distributes widely into tissues (with variable penetration into the eye and CSF), and is eliminated slowly, with a prolonged terminal half-life allowing tissue accumulation over repeated dosing. Lipid formulations alter the drug's distribution (reducing free-drug exposure to the kidneys) and pharmacokinetic profile compared with the conventional formulation.

Tericin for systemic infections is administered only by slow intravenous infusion in a hospital or closely monitored outpatient infusion setting; it is never given as an intravenous bolus/push. Topical formulations are applied directly to the affected skin area as directed. See Dosage and Administration for infusion practicalities and premedication guidance.

Tericin has several clinically significant drug interactions that require caution and monitoring:

• Nephrotoxic drugs (e.g., aminoglycosides, cyclosporine, cisplatin, other nephrotoxic agents): concurrent use with Tericin increases the risk of additive kidney damage; renal function should be closely monitored, and alternatives considered where possible.
• Corticosteroids and corticotropin: may potentiate Tericin-induced hypokalemia; electrolytes should be monitored closely during concurrent use.
• Digoxin and other drugs affected by hypokalemia (e.g., certain antiarrhythmics): Tericin-induced electrolyte disturbances can increase the risk of digoxin toxicity or arrhythmias; potassium levels should be monitored and corrected.
• Antineoplastic agents: concurrent use may increase the risk of nephrotoxicity, bronchospasm, and hypotension; used together only with caution and close monitoring.
• Flucytosine: often used deliberately in combination with Tericin (e.g., for cryptococcal meningitis) for synergy, but this combination can increase flucytosine toxicity because Tericin-related renal impairment reduces flucytosine clearance; renal function and flucytosine levels should be monitored.
• Other immunosuppressants/leukocyte transfusions: rare reports of acute pulmonary reactions when leukocyte transfusions are given close in time to Tericin infusions; administration timing should be separated where possible.

Side effects of Tericin are common, particularly with the conventional (deoxycholate) formulation, and range from infusion-related reactions to more serious organ toxicities.

Very common

• Infusion-related reactions: fever, chills/rigors, headache, myalgia, nausea, vomiting, and hypotension during or shortly after infusion
• Phlebitis/thrombophlebitis at the infusion site

Common / clinically important

• Nephrotoxicity: decreased kidney function, renal tubular acidosis, electrolyte wasting (see below) — the major dose-limiting toxicity of the conventional formulation (see Precautions and Warnings)
• Electrolyte disturbances: hypokalemia and hypomagnesemia
• Anemia (due to decreased erythropoietin production with prolonged use)
• Hepatotoxicity: abnormal liver function tests

Less common but serious

• Cardiac arrhythmias, particularly with rapid infusion rates
• Anaphylaxis and severe hypersensitivity reactions
• Bronchospasm

Pregnancy: Data on Tericin use in pregnancy are limited. It should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus, since systemic fungal infections themselves carry significant risk to both mother and fetus if untreated. A physician must always be consulted before use in pregnancy.

Lactation: It is not well established whether Tericin passes into human breast milk in clinically significant amounts. Because of the seriousness of infections treated with Tericin, a physician should weigh the benefit of treatment against any potential risk to the breastfeeding infant, and monitor the infant if breastfeeding continues during treatment.

Tericin therapy requires close specialist and inpatient (or closely supervised) monitoring because of its significant toxicity profile relative to the severity of infections it treats.

• Nephrotoxicity: The major dose-limiting toxicity of conventional Tericin. Regular monitoring of renal function and electrolytes is required throughout treatment. Adequate hydration and sodium loading before infusion can reduce risk. Lipid formulations generally have a more favorable renal safety profile but still require monitoring.
• Infusion-related reactions: Very common with intravenous Tericin, including fever, chills, rigors, and hypotension. Premedication with antipyretics and/or antihistamines is often used, particularly for early doses.
• Electrolyte disturbances: Hypokalemia and hypomagnesemia are common; monitor and replace electrolytes as needed.
• Bone marrow suppression: Anemia can occur with prolonged use; monitor blood counts.
• Hepatotoxicity: Monitor liver function periodically during treatment.
• Cardiac effects: Arrhythmias have been reported, particularly with rapid infusion; infuse slowly as directed.
• Specialist management: Given the severity of infections treated and the significant toxicity profile, Tericin requires management by, or in close consultation with, an infectious disease specialist, generally in an inpatient or closely supervised setting.
• Antifungal stewardship: Tericin should be reserved for confirmed or strongly suspected serious systemic fungal infections and should not be used empirically without an appropriate indication. Patients must take it exactly as prescribed and must not stop, extend, skip doses, or share it with others without medical advice.

Overdose or excessively rapid administration of Tericin can lead to severe cardiorespiratory toxicity, including cardiac arrest. There is no specific antidote for Tericin overdose. If overdose is suspected, seek immediate medical attention or contact emergency services/poison control right away. Management is supportive and typically requires hospitalization, with monitoring of cardiac, renal, and electrolyte status; hemodialysis is generally not effective at removing Tericin from the body.

Store unopened vials of Tericin in a refrigerator (2°C–8°C), protected from light, unless the specific product labeling states otherwise. Do not freeze. After reconstitution and/or dilution, follow the manufacturer's specific instructions regarding storage time, temperature, and light protection, as these vary by formulation. Keep out of reach of children.

Renal impairment

Tericin, especially the conventional formulation, is itself a significant cause of nephrotoxicity. In patients with pre-existing renal impairment, lipid-based formulations are generally preferred, and renal function must be monitored closely throughout treatment regardless of formulation used; dose adjustments are typically guided by serial renal function trends rather than a fixed reduction schedule.

Hepatic impairment

No well-established dose adjustment exists for hepatic impairment; Tericin should be used with caution, with periodic monitoring of liver function.

Elderly

Elderly patients may be at greater risk of renal impairment and should be monitored closely; dosing is generally the same as in other adults, individualized to renal function and clinical response.

Pediatric use

See Pediatric Uses.

Duration of Tericin therapy depends on the specific infection being treated, its severity, the patient's immune status, and clinical/mycological response, and can range from several weeks to several months for deep-seated systemic mycoses. The treating specialist determines the exact duration and when to switch to or continue with step-down oral antifungal therapy, if applicable. Treatment should not be stopped early without medical advice, even if symptoms improve.

Tericin deoxycholate powder for injection must be reconstituted with Sterile Water for Injection (without a bacteriostatic agent) as directed by the manufacturer — not with saline or solutions containing electrolytes, as this can cause the drug to precipitate. The reconstituted concentrate is then further diluted in 5% Dextrose in Water (D5W) for intravenous infusion, as saline-containing solutions are not compatible. Lipid-based formulations have their own specific reconstitution and dilution instructions (also typically using sterile water, then dilution in D5W) that must be followed exactly per the product's package insert. Use an in-line filter only where specified by the manufacturer, and inspect reconstituted solutions for particulate matter before use.

Polyene antifungal antibiotics (Amphotericin B, and by extension its lipid-based formulations)

Amphotericin B binds to ergosterol in the fungal cell membrane, forming pores that disrupt membrane integrity and cause leakage of intracellular potassium and other contents, resulting in fungal cell death. Its selectivity for ergosterol over human cholesterol underlies its antifungal activity, though some cholesterol binding contributes to its characteristic toxicities.

Category B (FDA legacy pregnancy category, for conventional and most lipid-based formulations)

Tericin is used in children, including neonates and infants, for the treatment of serious systemic fungal infections when clinically indicated, using weight-based (mg/kg) dosing similar in principle to adult dosing, adjusted per formulation and specific pediatric protocols. Because of the severity of infections for which it is used, Tericin is given to children under close specialist supervision with the same intensive monitoring (renal function, electrolytes, blood counts, infusion tolerance) recommended in adults.

Formal pediatric clinical trial data are more limited than in adults for some formulations and indications; in such cases, use in children is guided by the seriousness of the infection and specialist clinical judgment, consistent with the labeling position that safety and efficacy have not been formally established for every pediatric age group and indication.