Ambisome

Ambisome is one of the newer amphotericin B formulations, which is used widely as an anti-fungal drug. Presently amphotericin B (AMB) is the drug with the highest cure rate in kala-azar and up to 98% clinical and parasitological cure has been reported.

Like fungi, leishmania has a high percentage of ergosterol and is susceptible to this anti-fungal antibiotic.

AMB is also useful in mucocutaneous leishmaniasis. However, the need for prolonged hospitalization, monitoring, and repeated slow intravenous infusions may limit its application.

On the contrary, liposomal AMB is particularly suitable for kala-azar because it delivers the drug inside the reticuloendothelial cells in spleen and liver where the amastigotes live.

This medicine is available in injectable as well as powder forms. You can get this product only with your doctor’s prescription.

Ambisome is obtained from Streptomyces nodosus. It is active against a wide range of yeasts and fungi – Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Torulopsis, Rhodotorula, Aspergillus, Sporothrix, etc. Dermatophytes are inhibited in vitro, but concentrations of AMB attained in the infected skin are low and ineffective.

It is fungicidal at high and static at low concentrations.

There are some new amphotericin B formulations. In an attempt to improve the tolerability of intravenous infusion of AMB, 3 new lipid formulations of AMB have been produced. They are:

• Amphotericin B lipid complex (ABLC): contains 35% AMB incorporated in ribbon-like particles of dimyristoyl phospholipids.
• Amphotericin B colloidal dispersion (ABCD): disc shaped particles containing 50% each of AMB and cholesteryl sulfate are prepared as an aqueous dispersion.
• Liposomal amphotericin B (L-AMB): it has been produced to improve the tolerability of i.v. infusion of AMB, reduce its toxicity and achieve targeted delivery. It consists of 10% AMB incorporated in uniform sized (60-80 nM) unilamellar liposomes made up of lecithin and other biodegradable phospholipids. The special features of this preparation are:
  • It produces milder acute reaction on i.v. infusion.
  • It can be used in patients not a tolerating infusion of conventional AMB formulation.
  • It has lower nephrotoxicity.
  • It causes minimal anaemia.
  • It delivers AMB particularly to reticuloendothelial cells in liver and spleen –especially valuable for kala-azar and in immunocompromised patients.

If you are about to start this drug therapy, the risk and benefit ratio should be considered. This is a decision that your doctor will make with your active participation.

There are some important factors such as drug interaction, metabolic impairment, hypersensitivity reaction, pregnancy, lactation etc. which may alter the desired therapeutic effects of such medications.

Sometimes the presence of other health disorders affects the beneficial effects of this medicine and may even cause serious complications. Make sure you inform your doctor if you have any other medical problems.

The use of AMB liposome is contraindicated in patients with known hypersensitivity. This drug should not be given to patients receiving antineoplastics.

In addition, certain drugs should not be used concurrently with such medications. It is always recommended to consult with your doctor if you are in need of some drugs for another health problem in order to avoid unwanted serious drug interactions.

Moreover, animal reproduction studies performed have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Thus, this medicine can be used during pregnancy, if clearly needed.

Ambisome is the most effective drug for various types of systemic mycoses and is the gold standard of antifungal therapy.

The liposomal-AMB produces equivalent blood levels, has similar clinical efficacy with less acute reaction and renal toxicity than conventional preparation.

It thus appears more satisfactory, can be infused at higher rates (3-5 mg/kg/day), but is many times costlier than conventional AMB.

Its specific indications are:

• As empirical therapy in febrile neutropenic patients not responding to antibacterial antibiotics
• Critically ill deep mycosis cases
• In kala-azar

The frequency of your daily drug administration and the duration of drug therapy depend on the particular medical problem for which you are taking the medicine.

That’s why the therapeutic dose may vary with patient’s condition or requirement. Liposomal AMB of 10 mg, 25 mg and 50 mg per vial injection are available in the market. Usually, 0.5-1.0 mg/kg/day slow intravenous infusion is administered in the patients under direct supervision of a healthcare professional till 15-20 mg/kg is reached. The dosing of this medicine may vary from patient to patient.

In general, such medications are given to the patients in a hospital. You should take this medicine in time until the prescribed course is finished.

If you miss any dose of this medicine, you should take it as soon as possible. But if it is time for your next dose, then you should skip the missed dose and go back to your regular treatment schedule. You should store the medicine in a closed container at room temperature away from heat, moisture, and direct light.

All kinds of medicines should be kept out of the reach of children. Further, outdated medicines should be disposed of in an appropriate way.

Regular visits are recommended to make sure Ambisome is working properly or not. Additionally, you should be careful in order to avoid the unwanted drug interactions and other toxicity that may arise because of concurrent use of AMB with certain medicines.

It is safe to consult your doctor when you are in need of medicines for another health problem. On the contrary, you should tell your healthcare professional if you are taking any of the medicines listed below. It will help your doctor in making a decision to pick up the appropriate drug.

There are some drug interactions associated with AMB which is discussed below:

• Aminoglycosides, vancomycin, cyclosporine and other nephrotoxic drugs enhance the renal impairment caused by AMB.
• Flucytosine has supra-additive action with AMB in the case of fungi sensitive to both (AMB increases the penetration of 5-FC into the fungus).
• Rifampicin and minocycline, though not antifungal in their own right, potentiate AMB action.

There are some unwanted side-effects associated with Ambisome that usually do not need medical attention. These side-effects usually go away during the treatment episode as your body adjusts to the medicine. Your healthcare professional may advise you about the ways to prevent or reduce those unwanted side-effects.

Sometimes, you may need to consult with the doctor if you feel any serious toxic effects. Indeed, the toxicity of AMB is high but these effects are less likely to occur when the liposomal preparation is used.

Following side-effects are quite alarming and warrant immediate medical help:

• Acute reaction: This occurs with each infusion and consists of chills, fever, aches and pain all over, nausea, vomiting and dyspnea lasting for 2-5 hours, probably due to the release of cytokines (IL, TNF-alpha).
  When these are severe: The dose is increased gradually. Usually, the intensity of reaction decreases with continued medication. Injection of hydrocortisone 0.6 mg/kg with the infusion may reduce the intensity of the reaction. Thrombophlebitis of the injected vein can occur.
• Long-term toxicity: Nephrotoxicity is the most important. It occurs fairly uniformly and is dose-related: manifestations are –azotemia, reduced GFR, acidosis, hypokalemia, and inability to concentrate urine. It reverses slowly and often incompletely after stoppage of therapy.
• Anaemia: most patients develop slowly progressing anaemia which is due to bone marrow depression. It is largely reversible.

CNS toxicity occurs only on intrathecal injection – headache, vomiting, nerve palsies, etc.