Side effects

There are two types of drug which principally concern patients on the Email discussion list, corticosteroid (Prednisone) and anti-fungal drugs (Amphotericin and Itraconazole).

There is a short article on the side effects of taking Prednisone here.

The manufacturers list of adverse side effects of Amphotericin and Itraconazole can be found in the main Aspergillus website in the Treatment section (found by clicking the button on the list on the left hand side) under the subsection entitled antifungal drug data sheets. This is information which is legally required by the UK and USA governments to be made available to the doctors using the drugs. There are two lists, one for UK doctors and one for USA doctors as the detail of the legal requirement differs between the two countries. The actual information supplied is pretty much the same on both, as you might expect.

The language used in the drug data sheets is aimed at doctors and so tends to be difficult to read, so an attempt has been made to simplify the information here.

Amphotericin
This drug has a long history of being the first line of attack against many fungal infections, including Aspergillus.
The drug is insoluble in water so to dissolve it into a form which can be injected it is supplied mixed with sodium desoxycholate - many of the toxic effects of this drug are due the presence of desoxycholate rather than Amphotericin itself. This drug is always injected (intravenous drip) as it is not absorbable through the gut, so daily visits to the hospital are necessary.
Some attempts have been made to inhale Amphotericin to treat lung disease but only with limited success as the desoxycholate can be highly irritating to the lung tissue and is thus difficult to tolerate.
Solutions of Amphotericin have also been used for specific applications in the ear, eye, joints and in lung cavities.
There have been several attempts to dissolve Amphotericin using different methods and there are now four different forms available;

• Fungizone (the 'classic' desoxycholate version)
• Amphocil/Amphotec (a colloidal dispersion)
• Abelcet (a lipid complex i.e. a fatty emulsion)
• Ambisome (Amphotericin encased in liposomes (i.e. tiny bubbles)

All of the alternate forms of Amphotericin can be taken at higher dosage than the original form with less toxicity and thus can sometimes be more effective in killing the fungus. In order to be most effective Amphotericin must often be taken over a prolonged period (several months) so adverse reactions can be a significant problem. The most commonly observed adverse side effects of taking Fungizone intravenously (many of which can be prevented by taking medication beforehand) are as follows;

As you can appreciate many of these are severe problems, but as the administration of this drug takes place in hospital and/or under close medical supervision the risk is strictly limited - often by starting with a low dose and monitoring for adverse effects as the dose is gradually increased.

Itraconazole
Itraconazole (trade name Sporanox) is available in capsule and liquid forms so can be used as a convenient antifungal drug which does not require daily visits to hospital for injections. The downside is that care must often be taken to ensure enough Itraconazole is absorbed through the gut to be effective, This is usually done by regular blood tests during the early phase of taking the drug to determine what drug levels are reached in the blood.

As Itraconazole can be taken without daily medical supervision, the following are important to consider:

Do not take while pregnant - no danger has been shown for humans but laboratory animals showed a higher tendancy to have abnormal offspring at birth.

Do not take if you show hypersensitivity to the drug i.e. feel unwell shortly after taking it

Absorption is impaired when gastric acidity is decreased. In patients also receiving acid neutralising medicines (e.g. aluminium hydroxide) these should be administered at least 2 hours after the intake of Sporanox. In patients with achlorhydria (i.e. absence of acid in the stomach)such as certain AIDS patients and patients on secretion suppressors (e.g. H2-antagonists, proton-pump inhibitors), it is advisable to administer Sporanox with a cola beverage to aid absorption.

Rarely cases of hepatitis (inflammation of the liver) and jaundice (yellowing of the skin or whites of eyes) have been reported, mainly in patients treated for longer than one month. It is therefore advisable to monitor liver function in patients receiving continuous treatment of more than one month's duration. Additionally, if during treatment patients develop symptoms suggestive of hepatitis such as anorexia (loss of appetite), nausea (feeling sick), vomiting (being sick), fatigue (feeling tired), abdominal pain or dark urine, liver enzymes should be monitored promptly. If these are abnormal, treatment should be stopped.

In patients with raised liver enzymes, or with a known history of liver disease, or who have experienced liver toxicity with other drugs, treatment should not be started unless the expected benefit exceeds the risk of hepatic injury. In such instances liver enzyme monitoring is necessary.

Itraconazole is mainly broken down in the liver. Patients with liver disease sometimes do not break it down as quickly as they should, leading to an increase in the amount of itraconazole in their blood - this is checked by doing blood tests and corrected by adjusting the dose taken.

Some patients with kidney disease having some types of dialysis tend to 'wash out' the drug faster than they should. For this reason drug levels in the blood are monitored and the dose adjusted.

Adverse side effects