Consumer medicine information

Foscavir Injection

Foscarnet sodium

BRAND INFORMATION

Brand name

Foscavir

Active ingredient

Foscarnet sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Foscavir Injection.

What is in this leaflet

This leaflet answers some of the common questions people ask about Foscavir. It does not contain all the information that is known about Foscavir.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor will have weighed the risks of you being given Foscavir against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What is FOSCAVIR used for

Foscavir is used to treat infections caused by two viruses, Cytomegalovirus (CMV) and Herpes simplex virus (HSV).

These viruses infect different parts of the body and are most serious if your body's natural defences to fight disease are low (immunocompromised).

Your doctor will have explained what type of infection you have and where it is.

Foscavir belongs to a group of medicines called antivirals. It is injected into the body where it interferes with the way viral cells reproduce themselves and stops them increasing in number.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may prescribe this medicine for another use.

Foscavir is not addictive.

It is only available with a doctor's prescription.

There is not enough information to recommend the use of Foscavir in children.

Before you are given FOSCAVIR

When you must not be given it

Do not use Foscavir if you have an allergy to:

  • foscarnet
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue, or other parts of the body
  • rash, itching or hives of the skin

Foscavir should not be given to children. Safety and effectiveness in children have not been established.

You must not be given Foscavir while you are on haemodialysis. There is insufficient information on the use of Foscavir in patients undergoing haemodialysis.

If you are not sure whether you should be given Foscavir, talk to your doctor or nurse or pharmacist.

Before you start to use it

Tell your doctor before you are given Foscavir if you are pregnant, intend to become pregnant, are breastfeeding or intend to breastfeed.

  • Foscavir is not recommended during pregnancy.
  • Trying to become pregnant during Foscavir therapy is not recommended so you should use effective contraception methods.
  • Men treated with Foscavir should not father a child during or up to 6 months after therapy.
  • Do not have Foscavir if you are breastfeeding.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • any kidney disease or impairment
  • low calcium or magnesium levels in your blood
  • the need to control your sodium intake.

It may not be safe for you to use Foscavir if you have these conditions. Your doctor may do blood and urine tests before and during your treatment with Foscavir. This is to check how well your kidneys are working and the level of minerals in your blood.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Foscavir may interfere with each other. These include:

  • certain medicines used to treat infections such as intravenous pentamidine, amphotericin, aminoglycoside antibiotics (e.g. gentamicin, streptomycin) or aciclovir.
  • protease inhibitors (e.g. ritonavir, saquinavir)
  • certain diuretics which are used to help reduce fluid and treat blood pressure such as frusemide
  • ciclosporin, methotrexate or tacrolimus used to help prevent transplant rejection

These medicines may be affected by Foscavir or may affect how well it works.

Your doctor or pharmacist or nurse has more information on medicines to be careful with or avoid while being given this medicine.

How is FOSCAVIR given

Foscavir will be diluted with glucose 5% or normal saline, then injected slowly into a vein in your arm or leg by your doctor or nurse.

If you are in hospital, it may be injected into a major vein where it does not need to be diluted.

The dosage you will be given will depend on your body size, the infection you are being treated for, and how well your kidneys work.

How long to have it for

The initial course of treatment is over 2-3 weeks.

If you are being given Foscavir for CMV retinitis there will be two stages to your treatment.

If you are being given Foscavir to treat Herpes Simplex virus, there is only one stage to treatment.

If you forget to have Foscavir

If you think you have missed a dose, talk to your doctor straight away.

In case of overdose

If you take too much (overdose)

The doctor giving you Foscavir will be experienced in its use, so it is unlikely that you will be given an overdose.

However, if you are particularly sensitive to Foscavir, or you are given too much you may get tingling or a numb feeling like "pins and needles", dizziness, fits or seizures.

While you are given FOSCAVIR

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given Foscavir.

Tell any other doctors, dentists and pharmacists who treat you that you are being given this medicine.

Drink plenty of water while you are being given Foscavir. You may notice changes in the frequency or amount of urine while you are on Foscavir treatment. Drinking plenty of water makes kidney problems such as these less likely. Any problems with your kidneys will usually return to normal when treatment is stopped.

Keep any appointments with your doctor. Your doctor will want to monitor how this medicine is working and check for any side effects. They may do blood and urine tests to check how well your kidneys are working and the level of minerals in your blood.

Keep Foscavir solution and your urine away from your skin. Foscavir is very irritating to the skin. As most of the drug is removed from the body in your urine, you should take special care to wash and dry yourself well after going to the toilet.

If you get Foscavir solution on your skin or in your eyes by mistake, rinse your skin or wash your eyes straight away with water.

Things to be careful of

Be careful driving or operating machinery until you know how Foscavir affects you. This medicine may cause dizziness, tiredness and fits or seizures in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or nurse or pharmacist as soon as possible if you do not feel well while you are being given Foscavir.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • feeling or being sick
  • diarrhoea or constipation
  • stomach pain
  • indigestion
  • feeling weak or tired
  • headache
  • hives
  • skin rash or itching
  • genital discomfort and sores
  • decreased appetite
  • high temperature or chills
  • signs of other infections
  • changes in how you feel. This may include feeling depressed, confused, anxious, nervous, agitated or aggressive.
  • problems with your co-ordination
  • reduced feeling in the skin
  • increased thirst and dry mouth
  • generally feeling unwell
  • muscle problems. These include changes that are shown in blood tests and painful, sore, weak or twitching muscles.
  • swelling due to fluid build up in the feet or legs or other parts of the body
  • lower levels of white blood cells. The signs include infections, high temperature (fever) and changes in blood test results.
  • changes to red blood cells (shown in blood tests). This may make you feel tired or look pale.
  • changes in how well your liver is working (shown in blood tests)
  • low levels of platelets in your blood. This may make you bruise more easily.
  • shaking (tremors)
  • high blood pressure (often you only know this if it is measured)
  • reduction in how well your pancreas is working (shown in blood tests)
  • pathological alteration of the brain (encephalopathy)
  • swelling, pain or inflammation at injection site
  • inflammation of the oesophagus. This may be painful

These can be mild to severe side effects.

Tell your doctor or nurse immediately if you notice any of the following:

  • Signs of an allergic reaction which may include:
    - shortness of breath
    - wheezing or difficulty breathing
    - swelling of the face, lips, tongue, or other parts of the body
    - rash, itching or hives of the skin
  • Severe skin reactions that may include:
    - skin lesions or sores
    - red or purple rash that rapidly spreads
    - blisters of the skin and mucous membranes
    - swelling of the lips, face or throat
  • fast, slow, pounding or irregular heart beats or a change in rhythm e.g. Torsade de pointes (tests such as an ECG will also show changes in how well your heart is working)
  • tingling or numb feeling like "pins and needles"
  • severe pain in your abdomen (stomach area)
  • swelling and redness along a vein, which may be due to a blood clot
  • vomiting blood or material that looks like coffee grounds
  • blood in the stools or black bowel motions
  • feeling dizzy. This may be due to low blood pressure.
  • fits or seizures
  • a change in the colour or the amount of urine you produce, or pain when urinating. You may feel a pain in your lower back.
  • changes in how well your kidneys are working (shown in blood tests)
  • an imbalance of salts and minerals in your blood. The signs include weakness, cramps, thirst, tingling or itching of the skin and twitching of muscles.
  • too much acid in the blood. This may make you breathe more quickly.

These may be serious side effects. You may need urgent medical attention.

Tell your doctor or nurse or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some people.

After using FOSCAVIR

Storage

Foscavir is stored in the pharmacy or ward. It is kept in a cool dry place where the temperature stays below 25 degrees Celsius.

Disposal

Any Foscavir solution that is not used will be disposed of in a safe manner by your doctor, nurse or pharmacist.

Product description

What it looks like

Foscavir solution for injection is a clear, colourless solution containing foscarnet sodium 24 mg/mL as the active ingredient.

It comes in bottles of 250 mL.

Ingredients

In addition Foscavir contains the following inactive ingredients:

Hydrochloric acid

Water for Injections

Sponsor

Foscavir is supplied in Australia by:

Link Medical Products Pty Ltd
5 Apollo St
Warriewood NSW 2102

Australian Registration Number
Foscavir: AUST R 37310

This leaflet was prepared in November 2020.

Foscavir® is a trademark of Clinigen Healthcare Ltd

Published by MIMS December 2020

BRAND INFORMATION

Brand name

Foscavir

Active ingredient

Foscarnet sodium

Schedule

S4

 

1 Name of Medicine

Foscarnet sodium hexahydrate.

2 Qualitative and Quantitative Composition

Intravenous infusion solution containing 6 g foscarnet sodium hexahydrate (24 mg/mL) in 250 mL.
A clear, sterile, isotonic solution of foscarnet sodium in Water for Injections, adjusted to pH 7.4 with hydrochloric acid. No preservatives or buffers are contained in Foscavir.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Foscavir is indicated for:
treatment of cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS);
treatment of aciclovir resistant herpes simplex virus (HSV) infections (defined by clinical trial or in vitro resistance) in immunocompromised patients with human immunodeficiency virus (HIV) infection.

Note.

The indication for treatment of aciclovir resistant HSV infections in immunocompromised patients with HIV infections is based primarily on the results of one open label comparative study. This was of patients with HIV infections and herpetic lesions unresponsive to aciclovir administered intravenously for 10 days or more and in vitro documented resistance to aciclovir. Eight patients were randomised to foscarnet (40 mg/kg IV given eight hourly) and 6 were randomised to vidarabine (15 mg/kg IV daily). The results showed a significant difference in favour of the foscarnet treatment group for clinical and virological endpoints, especially in time to complete healing of lesions and time to complete loss of pain. In 177 other patients treated with foscarnet in non-comparative studies, results were sufficiently similar to support the efficacy of foscarnet in this indication.

4.2 Dose and Method of Administration

Contact with the skin and eyes may cause local irritation and a burning sensation. If accidental contact occurs, the exposed area should be rinsed immediately with cold water.

Method of administration.

Foscavir must be given by the intravenous route only, either via a central venous line or directly into peripheral veins.
When peripheral veins are used, Foscavir 24 mg/mL must be diluted with glucose (dextrose) 5% or normal saline to a concentration of 12 mg/mL immediately prior to administration. (See Section 4.4 Special Warnings and Precautions for Use regarding total daily sodium intake.)
Foscavir 24 mg/mL solution may be given without dilution via a central vein. Infusion time should not be less than one hour.

Adults.

CMV retinitis.

Induction therapy.

Foscarnet can be administered over 2-3 weeks, depending on clinical response, as intermittent infusions every 8 hours at a dose of 60 mg/kg in patients with normal renal function (see Table 1).
The dose of foscarnet should be adjusted to the renal function as assessed by estimated creatinine clearance.

Maintenance therapy.

For maintenance therapy, foscarnet is administered seven days a week as a once daily infusion over 2 hours at a dose determined by renal function as assessed by estimated creatinine clearance. In patients with normal renal function the dose range is 90-120 mg/kg/day. It is recommended to initiate therapy at 90 mg/kg and increase up to 120 mg/kg in patients in whom retinitis is progressing and who show good tolerance to the lower dose.
The dosage used can be calculated from Table 2 or from experience obtained with the patient during the induction phase by correlating their renal function with plasma levels.
These dosage recommendations are approximate and actual dosing should always be based on the clinical situation.
HSV infections.

Induction therapy.

Foscarnet should be administered at a dose of 40 mg/kg, by slow intravenous infusion (over one hour), every 8 hours in patients with normal renal function (see Table 1). Infusions should be maintained for 2-3 weeks or until the lesions have healed.

Maintenance therapy.

The efficacy of Foscavir maintenance therapy in the treatment of aciclovir resistant HSV infections has not been established.

Caution.

Do not administer foscarnet by rapid intravenous infusion.
Foscarnet is not recommended for use in patients undergoing haemodialysis as dosage guidelines have not been established.

Hydration.

Renal toxicity can be reduced by adequate hydration of the patient. Prior to the first foscarnet infusion it is recommended that diuresis be established by hydration with 0.5-1.0 litre normal saline. Subsequently add 0.5-1.0 litre normal saline to each infusion. In compliant patients, oral hydration with similar hydration regimens has been used. Clinically dehydrated patients should have their condition corrected before initiating Foscavir therapy.

Duration of treatment.

An initial induction treatment period of 2-3 weeks is recommended, depending on the clinical response, followed by maintenance therapy for as long as considered appropriate.

Elderly.

As for adults.

Paediatric population.

The safety and efficacy of foscarnet in children have not been established. Please see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties.

Renal or hepatic impairment.

The dose must be reduced in patients with renal insufficiency according to the creatinine clearance level as described in Tables 1 and 2. Dose adjustment is not required in patients with hepatic insufficiency.

Compatibility.

See Section 6.2 Incompatibilities for information on compatibility with other pharmaceutical products.

4.3 Contraindications

Hypersensitivity to foscarnet.
Long-term treatment with foscarnet is contraindicated in patients with a reasonable prognosis (e.g. bone marrow transplant patients) because the animal toxicological data are limited and insufficient to ensure safety in man over an extended period.

4.4 Special Warnings and Precautions for Use

Co-administration with intravenous pentamidine.

For possible drug interaction of Foscavir and intravenous pentamidine, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

Use in renal impairment.

Foscarnet should be used with caution in patients with reduced renal function. Since renal function impairment may occur at any time during foscarnet administration, serum creatinine should be monitored every second day during induction therapy and once weekly during maintenance therapy. Appropriate dose adjustments should be made if renal function is affected. (See Section 4.2 Dose and Method of Administration).
To minimise the potential of renal function impairment, adequate hydration should be maintained in all patients. The renal function of patients with renal disease or receiving concomitant treatment with other nephrotoxic medicinal products must be closely monitored (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Dosage guidelines have not been established for the use of foscarnet in patients undergoing renal dialysis.

Mineral and electrolyte abnormalities.

Due to Foscavir's propensity to chelate bivalent metal ions, such as calcium, Foscavir administration may be associated with an acute decrease of ionised serum calcium proportional to the rate of Foscavir infusion, which may not be reflected in total serum calcium levels. The electrolytes, especially calcium and magnesium, should be assessed prior to and during Foscavir therapy and deficiencies corrected.
Foscarnet has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and Torsade de pointes in patients taking foscarnet. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors.
Patients with known existing prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or bradycardia, as well as patients with underlying cardiac diseases such as congestive heart failure should be carefully monitored due to increased risk of ventricular arrhythmia. Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or bradycardia are known to be conditions increasing the proarrhythmic risk.
Patients should be advised to promptly report any cardiac symptoms.
Barium is present in Foscavir glass bottles, and content increases on storage. Barium is known to be an inhibitor of potassium channels and can induce neuromuscular blockade and membrane depolarisation. Treating physicians should monitor for electrolyte and electrocardiogram (ECG) abnormalities and potential effects on potassium levels (hypokalaemia).
Should patients experience extremity paraesthesia or nausea, it is recommended to reduce the speed of infusion.

Genital irritation and ulceration.

Foscavir is excreted in high concentrations in the urine and may be associated with significant genital irritation and/or ulceration. To prevent irritation and ulceration, close attention to personal hygiene is recommended and cleaning of the genital area after each micturition is recommended.

Sodium content.

Foscarnet is a trisodium salt. Each mL of Foscavir (24 mg/mL foscarnet sodium) contains 240 micromole (5.5 mg) of sodium. Foscarnet use should be avoided when a saline load cannot be tolerated (e.g. in cardiomyopathy). This should also be taken into consideration by patients on a controlled sodium diet.

Diuretics.

When diuretics are indicated, thiazides are recommended over loop diuretics because the latter inhibit renal tubular secretion, and may impair elimination of Foscavir, potentially leading to toxicity.

Seizures.

Seizures, related to plasma minerals and electrolytes, have been associated with Foscavir treatment. Cases of status epilepticus have been reported. Therefore, patients must be carefully monitored for such changes and their potential sequelae. Mineral and electrolyte supplementation may be required (see Section 4.4 Special Warnings and Precautions for Use, Mineral and electrolyte abnormalities).

Resistance.

Development of resistance: if the administration of Foscavir does not lead to a therapeutic response or leads to a worsened condition after an initial response, this may result from a reduced sensitivity of viruses towards foscarnet. In this case, termination of Foscavir therapy and a change to an appropriate other medicinal product should be considered.

Use in the elderly.

No studies of the efficacy or safety of Foscavir solely in persons 65 years of age or older have been conducted. However, Foscavir has been used in patients aged 65 years and older. The pattern of adverse events seen in these patients is consistent across all age groups. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and renal function should be monitored (see Section 4.2 Dose and Method of Administration).

Paediatric use.

The safety of Foscavir and its effect on skeletal development have not been investigated in children. There are insufficient data available either in vivo or in vitro to establish any possible effect in growing bone. Please see Section 5.2 Pharmacokinetic Properties.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

1. A possible drug interaction of Foscavir and intravenous pentamidine has been described. Concomitant treatment of four patients in the United Kingdom with Foscavir and intravenous pentamidine may have caused hypocalcaemia; one patient died with severe hypocalcaemia. Toxicity associated with concomitant use of aerosolised pentamidine has not been reported.
Since Foscavir can reduce serum levels of ionized calcium, extreme caution is advised when used concurrently with other drugs known to reduce serum calcium levels, like IV pentamidine. Renal impairment and symptomatic hypocalcaemia (Trousseau's and Chvostek's signs) have been observed during concurrent treatment with foscarnet and IV pentamidine. Fatalities have been reported in post-marketing surveillance during concomitant therapy with Foscavir and pentamidine.
2. There is no pharmacokinetic interaction when foscarnet is used in combination with zidovudine (AZT), ganciclovir, didanosine (ddl), zalcitabine (ddC) or probenecid.
3. Since Foscavir can impair renal function, additive renal toxicity may occur when used in combination with other nephrotoxic drugs such as aminoglycosides, amphotericin B, ciclosporin A, aciclovir, methotrexate and tacrolimus.
4. Due to their mechanism of action, loop diuretics should not be used during Foscavir therapy.
5. Abnormal renal function has been reported in connection with the use of Foscavir in combination with ritonavir and/or saquinavir.
6. Pharmaceutical interactions (incompatibilities for infusion) are described in Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Foscavir did not adversely affect fertility and general reproductive performance in rats. The results of peri- and post-natal studies in rats were also negative. However, these studies used exposure levels that are inadequate to define the potential for impairment of fertility at human drug exposure levels.
(Category B3)
Daily subcutaneous doses up to 75 mg/kg post-partum administered to female rats prior to and during mating, during gestation and 21 days post-partum caused a slight increase (< 5%) in the number of skeletal abnormalities compared with the control group. Daily subcutaneous doses up to 75 mg/kg administered to rabbits and 150 mg/kg administered to rats during gestation caused an increase in the frequency of skeletal abnormalities/ variations. These studies are inadequate to define the potential teratogenicity at levels to which women will be exposed.
On the basis of estimated drug exposure (as measured by AUC), the 150 mg/kg dose in rats and 75 mg/kg dose in rabbits were approximately one-eighth (rat) and one-third (rabbit) the estimated maximal daily human exposure.
Women capable of childbearing should use effective contraception methods during Foscavir therapy. Men treated with Foscavir should not father a child during or up to 6 months after therapy.
Since there is no clinical experience or investigational data available, Foscavir should not be given to pregnant women.
 Animal studies indicate foscarnet passes into the milk of lactating rats at concentrations approximately 3 times higher than those in maternal plasma. No information is available on levels of foscarnet which may appear in human breast milk. Since there is no clinical experience or investigational data available, Foscavir should not be given during lactation.

4.7 Effects on Ability to Drive and Use Machines

Foscarnet has no sedating effects and generally there is no reason to believe that the ability to drive or use machinery is impaired following the administration of foscarnet. However, adverse effects such as dizziness and convulsions may occur during therapy and the physician is advised to discuss this issue with the patient.

4.8 Adverse Effects (Undesirable Effects)

The majority of patients who receive Foscavir are severely immuno-compromised and suffering from serious viral infections. Patients' physical status, the severity of underlying disease, other infections and concurrent therapies contribute to adverse events observed during use of Foscavir.

Clinical trials experience.

The undesirable effects reported with Foscavir during clinical trials and post-marketing surveillance are listed by system organ class (SOC) and in order of frequency, using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
The adverse events and frequencies shown in Table 3 are based on the foscarnet primary clinical trial database. This includes adverse experiences reported at any time during induction, maintenance or follow-up treatment in 5 clinical trials involving 188 patients with CMV retinitis.
Please note that in these clinical trials, hydration and attention to electrolyte balance was not consistently given; the frequency of some adverse events will be lower when current recommendations are followed (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

Postmarketing and other experience.

Reporting rates for events detected in studies other than those in the primary clinical trial database and/or from spontaneous post-marketing reports are shown in Table 4.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
Overdose has been reported during the use of Foscavir, the highest being some 20 times the recommended dose. Some of the cases were relative overdoses, in that the dose of the drug used had not been promptly adjusted for a patient experiencing reduced renal function. There are cases where it has been reported that no clinical sequelae occurred following the overdose.
The pattern of adverse events reported in association with overdose of Foscavir is in accordance with the known adverse event profile of the drug.
Haemodialysis increases foscarnet elimination and may be of benefit in relevant cases.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Foscarnet is an antiviral agent with a broad antiviral spectrum which inhibits all known human viruses of the herpes group (herpes simplex type 1 and 2, human herpes virus 6), varicella zoster virus, Epstein-Barr virus and cytomegalovirus (CMV) and some retroviruses including human immunodeficiency virus (HIV) at concentrations not affecting normal cell growth. Foscarnet also inhibits the viral DNA polymerases from hepatitis B virus. Foscarnet exerts its antiviral activity by a direct inhibition of viral specific DNA polymerase and reverse transcriptase. Foscarnet does not require activation by thymidine kinase or other kinases and therefore is active in vitro against herpes simplex virus (HSV) mutants deficient in thymidine kinase (TK).
In vitro systems are of limited value in predicting in vivo effectiveness. The mean foscarnet 50% inhibition value (IC50) for more than one hundred clinical CMV isolates is approximately 270 micromol/L, while a reversible inhibition of normal cell growth is observed at about 1000 micromol/L.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Following IV administration in man, foscarnet plasma concentrations follow a multi-exponential decay pattern with several half-lives. The initial decline has a half-life of approximately 2-4 hours if renal function is normal. An apparent terminal half-life of approximately 1 to 8 days has been recorded, probably reflecting the slow release of foscarnet from bone.
The plasma clearance of foscarnet after intravenous administration to man varies between 130-160 mL/min. The mean volume of distribution of foscarnet at steady state varies between 0.4-0.6 L/kg.
Foscarnet is distributed to the cerebrospinal fluid and concentrations ranging from 10 to 70% of the concurrent plasma concentrations have been observed in HIV infected patients.
Foscarnet is mainly eliminated by the renal route, by glomerular filtration and tubular secretion. Renal clearance is approximately 130 mL/min.
There is no metabolic conversion of foscarnet, and the binding to human plasma proteins is less than 20%.
In man, up to 20% of the cumulative intravenous dose has not been excreted in the urine 7 days after cessation of infusion, and can be assumed to have been deposited in bone and cartilage. Deposition is greater in young and growing animals. This effect has only been seen in dogs.
The bone changes were characterised as increased osteoclast activity and bone resorption. The reason for these changes may be that Foscavir, due to its structural similarity to phosphate, is incorporated into the hydroxyapatite. Audioradiographic and other studies have shown Foscavir to have a pronounced affinity for bone tissue. Recovery studies revealed that bone changes were reversible. Foscarnet sodium has been demonstrated to adversely affect development of tooth enamel in mice and rats. The effects of this deposition on skeletal development have not been studied.
Following induction therapy, either administered as a continuous infusion or as intermittent infusions every eight hours, foscarnet has produced stabilisation of retinal lesions in approximately 90% of cases treated.
However, since CMV usually causes latent infections and since foscarnet, like other anti-CMV agents, exerts a virustatic effect, relapses are likely to be seen after therapy in the majority of patients with persistent immunodeficiency once treatment is discontinued.
Institution of once daily maintenance therapy following completion of induction therapy has produced a delay in time to retinitis progression. In patients experiencing progression of retinitis while receiving maintenance therapy or off therapy, re-institution of induction therapy has shown equal efficacy as the initial course.

Special populations - adults with impaired renal function.

The pharmacokinetic properties of foscarnet have been determined in a small group of adult subjects with normal and impaired renal function, as summarised in Table 5.
Total systemic clearance (CL) of foscarnet decreased and half-life increased with diminishing renal function (as expressed by creatinine clearance). Based on these observations, it is necessary to modify the dosage of foscarnet in patients with renal impairment (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

In several animal species foscarnet is rapidly cleared from blood and other soft tissues after intravenous administration. However, dose proportional concentrations have been observed in bone and cartilage in all animal species studied.
Investigations in dogs have shown that foscarnet has no effect on calcium homoeostasis.

Genotoxicity.

Mutagenicity studies showed that foscarnet has a genotoxic potential. The genotoxic effect demonstrated in these studies is possibly due to inhibition of the DNA polymerase in the cell line used. Foscarnet acts therapeutically by inhibition of the herpes virus specific DNA polymerase. The human cellular polymerase α is about 100 times less sensitive to foscarnet.
Foscarnet was shown to have clastogenic activity in the mouse micronucleus test and in an in vitro cytogenetics assay using Chinese hamster cells.

Carcinogenicity.

No oncogenic potential has been demonstrated in carcinogenicity studies in mice at oral doses up to 250 mg/kg/day for 18 months, or in rats at oral doses up to 500 mg/kg/day for 24 months.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injection, hydrochloric acid.

6.2 Incompatibilities

Foscavir is not compatible with glucose 30% solution, amphotericin B, aciclovir sodium, ganciclovir, pentamidine isethionate, trimethoprim/ sulfamethoxazole, vancomycin hydrochloride, or with solutions containing calcium. It is recommended that other drugs should not be infused concomitantly in the same line.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
Foscavir contains no preservative and once the sterility seal of a bottle has been broken the solution should be discarded within 24 hours.
For doses prepared by a hospital pharmacy, foscarnet may be transferred to plastic infusion bags for use within 24 hours.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate.

6.5 Nature and Contents of Container

Type I clear glass bottle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Foscarnet sodium is trisodium phosphonoformate hexahydrate or phosphonoformic acid trisodium salt hexahydrate, MW 300.0.

Chemical structure.


CAS number.

34156-56-4.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes