Foscarnet Tillomed: Uses, Dosage & Side Effects

What Is Foscarnet Tillomed and What Is It Used For?

Foscarnet Tillomed contains the active substance foscarnet sodium (also known as phosphonoformic acid trisodium salt), which is a synthetic pyrophosphate analogue with broad-spectrum antiviral activity. Foscarnet was originally discovered in the 1960s and was developed as an antiviral agent during the 1980s, largely in response to the urgent need for treatments for opportunistic infections in patients with AIDS. It received regulatory approval for the treatment of CMV retinitis and has since become an essential component of the antiviral armamentarium, particularly when first-line agents are ineffective or poorly tolerated.

The mechanism of action of foscarnet is fundamentally different from that of nucleoside analogue antivirals such as acyclovir, ganciclovir, and cidofovir. While those drugs require phosphorylation by viral or cellular kinases to become active, foscarnet acts directly on viral DNA polymerase (and in the case of retroviruses, reverse transcriptase) without any need for intracellular activation. Specifically, foscarnet binds reversibly to the pyrophosphate-binding site of the viral DNA polymerase, blocking the cleavage of pyrophosphate from deoxynucleoside triphosphates (dNTPs). This prevents the elongation of the growing viral DNA chain and halts viral replication. Because foscarnet does not require phosphorylation by viral thymidine kinase (TK), it retains activity against viruses that have developed resistance to nucleoside analogues through mutations in the TK gene.

Foscarnet demonstrates in vitro activity against a range of herpesviruses, including cytomegalovirus (CMV, also known as human herpesvirus 5), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6). It also has activity against hepatitis B virus (HBV) and, at higher concentrations, against HIV reverse transcriptase, although it is not used clinically as an anti-HIV agent due to toxicity concerns and the availability of more effective antiretroviral drugs.

The primary approved indications for Foscarnet Tillomed include:

• CMV retinitis in immunocompromised patients: Cytomegalovirus retinitis is a sight-threatening infection of the retina that occurs predominantly in individuals with severely compromised immune systems, most commonly patients with advanced HIV/AIDS (typically CD4 counts below 50 cells/µL). Before the era of effective antiretroviral therapy (ART), CMV retinitis affected up to 30% of AIDS patients. Foscarnet is approved as both induction and maintenance therapy for this condition. The landmark SOCA (Studies of the Ocular Complications of AIDS) trials demonstrated that foscarnet was as effective as ganciclovir in controlling CMV retinitis, and one study (SOCA-FGCRT) suggested a survival advantage for foscarnet-treated patients, possibly due to intrinsic anti-HIV activity.
• Acyclovir-resistant mucocutaneous HSV infections: Herpes simplex virus infections that fail to respond to standard acyclovir therapy are most commonly encountered in immunocompromised patients, particularly those with AIDS, those undergoing organ or stem cell transplantation, and those receiving intensive chemotherapy. Resistance to acyclovir typically arises through mutations in the viral thymidine kinase gene, which also confers cross-resistance to other nucleoside analogues such as valacyclovir and famciclovir. Because foscarnet bypasses the TK activation step, it remains effective against these resistant strains and is considered the treatment of choice for acyclovir-resistant HSV.
• Ganciclovir-resistant CMV infections (off-label but guideline-supported): In the setting of solid organ transplantation and hematopoietic stem cell transplantation, CMV disease resistant to ganciclovir and valganciclovir represents a significant clinical challenge. The European Conference on Infections in Leukaemia (ECIL) guidelines and the Transplant Infectious Disease (TID) guidelines recommend foscarnet as a preferred alternative agent for ganciclovir-resistant CMV disease.

In contemporary clinical practice, foscarnet remains a critically important antiviral, particularly in the transplantation setting. With the growing population of immunocompromised patients worldwide – including those receiving organ transplants, hematopoietic stem cell transplants, chimeric antigen receptor (CAR) T-cell therapy, and other immunosuppressive treatments – the incidence of drug-resistant herpesvirus infections has increased. Foscarnet, along with cidofovir, serves as the principal rescue therapy for these infections when first-line agents have failed.

What Should You Know Before Receiving Foscarnet Tillomed?

Contraindications

There are specific situations in which Foscarnet Tillomed must not be used. Your treating physician must assess these before initiating therapy.

• Hypersensitivity: Do not receive Foscarnet Tillomed if you are allergic to foscarnet sodium or any of the excipients in the formulation. Although true anaphylactic reactions to foscarnet are very rare, any history of hypersensitivity to the drug is an absolute contraindication.
• Severe renal impairment with inability to hydrate: Patients with severe kidney failure who cannot receive adequate intravenous hydration should not be given foscarnet, as the drug’s nephrotoxicity would pose an unacceptable risk without the protective effect of hydration.

Warnings and Precautions

Before and during treatment with Foscarnet Tillomed, inform your doctor if any of the following apply to you:

• Electrolyte disturbances: Foscarnet chelates (binds) divalent cations, leading to significant decreases in ionized calcium, magnesium, potassium, and phosphate. Hypocalcemia can cause perioral tingling, numbness, muscle cramps, tetany, and seizures. Hypomagnesemia and hypokalemia can cause cardiac arrhythmias. Electrolytes must be monitored before each infusion and corrected promptly. Patients should be advised to report any tingling, numbness, or muscle spasms immediately.
• Seizures: Seizures have been reported in approximately 5–10% of patients receiving foscarnet, typically in association with electrolyte abnormalities (particularly hypocalcemia) or underlying central nervous system disease. Patients with a history of seizures or those receiving other medications that lower the seizure threshold are at increased risk.
• Cardiac abnormalities: Electrolyte imbalances caused by foscarnet, particularly changes in calcium, magnesium, and potassium, can prolong the QT interval and increase the risk of cardiac arrhythmias including torsades de pointes. ECG monitoring should be considered in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications.
• Genital ulceration: Foscarnet is excreted in high concentrations in the urine. Contact of the drug with genital and perineal skin can cause local irritation and painful ulceration. Both men and women should be advised to maintain careful personal hygiene and to wash the genital area thoroughly after each urination during foscarnet therapy. This side effect is not an allergic reaction and resolves when the drug is discontinued.
• Anemia and bone marrow effects: Foscarnet can cause anemia, which may be severe enough to require transfusion in some patients. Regular monitoring of haemoglobin and complete blood counts is recommended. Although foscarnet is generally considered less myelosuppressive than ganciclovir, cytopenias have been reported.
• Hepatotoxicity: Elevations in liver enzymes (AST, ALT) have been reported during foscarnet therapy. Liver function should be monitored periodically. In rare cases, more significant hepatic dysfunction has occurred.
• Central nervous system effects: In addition to seizures, patients may experience headache, dizziness, fatigue, confusion, hallucinations, and peripheral neuropathy. These symptoms should be reported promptly.
• Infusion site reactions: Local reactions including phlebitis, pain, and thrombosis at the infusion site have been reported. Foscarnet is an alkaline solution and should preferably be administered through a central venous catheter. If peripheral infusion is necessary, the 24 mg/ml solution should be diluted with glucose 5% or sodium chloride 0.9% to reduce the concentration and minimize vein irritation.

Your doctor will perform regular blood tests including serum creatinine, electrolytes (calcium, magnesium, potassium, phosphate), and complete blood counts before every infusion and periodically throughout your treatment course.

Pregnancy and Breastfeeding

Foscarnet should not be used during pregnancy unless the potential benefit clearly justifies the potential risk to the fetus. Animal reproductive studies have shown that foscarnet crosses the placenta and can cause skeletal abnormalities (including reduced ossification) in animal offspring at doses approaching the human therapeutic range. There are very limited human data on the use of foscarnet in pregnancy. Women of childbearing potential should use effective contraception during treatment.

It is not known whether foscarnet is excreted in human breast milk. Given the potential for serious adverse reactions in the nursing infant, including nephrotoxicity and electrolyte disturbances, breastfeeding should be discontinued during foscarnet therapy. In the case of HIV-positive mothers, breastfeeding is generally not recommended regardless of medication, due to the risk of HIV transmission.

Driving and Operating Machinery

Foscarnet may cause dizziness, fatigue, seizures, and other central nervous system effects that could impair your ability to drive safely or operate heavy machinery. If you experience any of these symptoms during treatment, do not drive or use machines. Discuss with your doctor whether it is safe for you to drive.

How Does Foscarnet Tillomed Interact with Other Drugs?

Drug interactions with foscarnet primarily involve two mechanisms: additive nephrotoxicity when combined with other kidney-damaging drugs, and additive electrolyte disturbances (particularly hypocalcemia) when combined with agents that also affect calcium or other mineral homeostasis. Because many immunocompromised patients require multiple medications, careful drug interaction assessment is essential before and during foscarnet therapy.

Major Interactions

Minor Interactions

It is important to note that foscarnet is not significantly metabolized by the cytochrome P450 enzyme system, and therefore does not have the typical CYP-mediated drug interactions that many other medications possess. The drug is eliminated almost entirely by the kidneys through glomerular filtration and tubular secretion. This means that the most clinically relevant drug interactions are those involving other nephrotoxic agents or drugs that affect electrolyte balance.

In the transplantation setting, where patients are routinely receiving calcineurin inhibitors (ciclosporin or tacrolimus) alongside numerous other nephrotoxic agents, the combination with foscarnet requires particularly careful management. Frequent monitoring of renal function (at least before every infusion) and close collaboration between the transplant team and infectious disease specialists is essential to balance the antiviral benefit against the risk of cumulative renal damage.

What Is the Correct Dosage of Foscarnet Tillomed?

Foscarnet Tillomed must always be administered by a healthcare professional as an intravenous infusion in a hospital or supervised clinical setting. The drug must be given using a controlled-rate infusion pump to ensure precise delivery over the recommended duration. Rapid intravenous injection is strictly contraindicated as it can cause severe, potentially fatal electrolyte disturbances and renal toxicity. All doses are calculated based on body weight and must be adjusted according to the patient’s renal function (creatinine clearance).

CMV Retinitis – Induction Therapy

CMV Retinitis – Maintenance Therapy

Acyclovir-Resistant HSV Infections

Dose Adjustments for Renal Impairment

Dose adjustment based on creatinine clearance (CrCl) is mandatory. The manufacturer provides detailed dosing tables based on CrCl values. As a general principle:

Serum creatinine must be measured at least every other day during induction therapy and at least once weekly during maintenance therapy. If creatinine clearance drops below the threshold for safe dosing, foscarnet must be withheld and may be restarted at a reduced dose once renal function recovers.

Children

There is limited clinical experience with foscarnet in children, and it is not routinely recommended for paediatric use. When used in paediatric patients (typically in the setting of refractory CMV infection after haematopoietic stem cell transplantation), dosing has generally been extrapolated from adult data on a mg/kg basis with careful individual dose adjustment. Any paediatric use should be managed by specialist infectious disease physicians and monitored with enhanced frequency of renal and electrolyte assessments. The risk of renal toxicity and growth-related effects on bone mineralisation must be carefully weighed against the benefit of treatment.

Elderly Patients

Elderly patients are more likely to have reduced renal function, and creatinine clearance often declines with age even when serum creatinine appears normal. Dose adjustment based on accurately measured or estimated creatinine clearance is particularly important in this population. Enhanced monitoring of renal function and electrolytes is recommended. The risk of dehydration, which compounds foscarnet’s nephrotoxicity, is also higher in elderly patients.

Missed Dose

If a scheduled dose of foscarnet is missed, contact your healthcare team as soon as possible. Do not attempt to “make up” a missed dose by doubling the next infusion, as this would significantly increase the risk of nephrotoxicity and electrolyte disturbances. Your doctor will determine when the next dose should be given based on your clinical situation and current renal function.

Overdose

Overdose with foscarnet can be life-threatening. Excessive doses or inappropriately rapid infusion may cause severe hypocalcemia (with tetany, seizures, and cardiac arrest), acute kidney injury, and other severe electrolyte disturbances. There is no specific antidote for foscarnet overdose. Treatment is supportive and includes immediate cessation of the infusion, aggressive intravenous calcium replacement to correct hypocalcemia, intravenous fluids to support renal perfusion, monitoring and correction of all electrolyte abnormalities, and dialysis may be considered in cases of severe renal failure, as foscarnet is partially cleared by haemodialysis.

What Are the Side Effects of Foscarnet Tillomed?

Like all medicines, Foscarnet Tillomed can cause side effects, although not everyone experiences all of them. The side effect profile of foscarnet is dominated by its effects on the kidneys and electrolyte balance. Many side effects are dose-dependent and can be managed through careful dose adjustment, adequate hydration, and prompt correction of electrolyte abnormalities. Your medical team will monitor you closely throughout treatment.

Side Effects by Frequency

Nephrotoxicity in Detail

Renal impairment is the most clinically significant adverse effect of foscarnet and the primary dose-limiting toxicity. The mechanism involves direct toxicity to the renal tubular epithelium, as well as crystal deposition within the renal tubules. The incidence of some degree of renal impairment approaches 33% in clinical studies. In most cases, the renal dysfunction is reversible if the drug is discontinued promptly and the patient is adequately hydrated. However, irreversible renal damage has been reported, particularly in patients who received inadequate hydration, had pre-existing renal disease, or were concurrently receiving other nephrotoxic agents.

Risk factors for foscarnet-induced nephrotoxicity include dehydration, pre-existing kidney disease, rapid infusion rates, high doses, prolonged treatment duration, and concurrent use of other nephrotoxic drugs (aminoglycosides, amphotericin B, ciclosporin, tacrolimus, non-steroidal anti-inflammatory drugs). The cornerstone of prevention is adequate hydration: a pre-infusion bolus of 0.5–1.0 litre of normal saline is recommended before each infusion, along with maintenance of adequate fluid intake throughout treatment. Some centres also recommend concurrent oral hydration.

Electrolyte Disturbances in Detail

Foscarnet has a unique ability to chelate (bind) divalent metal cations, particularly ionized calcium. This chelation occurs rapidly during infusion and is responsible for many of the acute symptoms experienced by patients. The reduction in ionized calcium can cause perioral tingling, numbness of the extremities, muscle spasms, carpopedal spasm (Trousseau sign), tetany, and in severe cases, generalized seizures. These symptoms are often described by patients as a “pins and needles” sensation that develops during the infusion and typically resolves within a few hours afterwards.

In addition to calcium chelation, foscarnet causes renal wasting of magnesium, potassium, and phosphate through its effects on the renal tubules. These electrolyte losses are independent of the chelation effect and can be cumulative over prolonged treatment courses. Hypomagnesemia can worsen hypocalcemia (since magnesium is required for normal parathyroid hormone function and calcium homeostasis) and increase the risk of cardiac arrhythmias. Hypokalemia can cause muscle weakness, cardiac arrhythmias, and paralysis.

How Should You Store Foscarnet Tillomed?

Foscarnet Tillomed 24 mg/ml solution for infusion should be stored at room temperature, between 15°C and 25°C (59°F to 77°F). The solution should not be refrigerated or frozen, as low temperatures may cause crystallisation of the foscarnet sodium. If crystals are observed in the solution, it should be warmed to room temperature and gently swirled until the crystals dissolve completely before use. If crystals do not dissolve, the solution should not be used.

Keep the vials or bottles in the original outer carton to protect from light. The solution is clear and colourless to slightly yellow; do not use if the solution appears discoloured, cloudy, or contains particulate matter that does not dissolve on warming.

Do not use Foscarnet Tillomed after the expiry date stated on the label and carton. The expiry date refers to the last day of that month. Once opened, the solution should be used immediately. Any unused portion should be discarded according to local pharmaceutical waste regulations. If the 24 mg/ml solution is diluted with glucose 5% or sodium chloride 0.9% for peripheral administration, the diluted solution should be used within 24 hours of preparation and should not be stored.

As with all medications, keep Foscarnet Tillomed out of the sight and reach of children. Do not dispose of unused medicines via household waste or wastewater. Ask your pharmacist or hospital pharmacy about proper disposal to help protect the environment.

What Does Foscarnet Tillomed Contain?

Each millilitre of Foscarnet Tillomed solution for infusion contains:

• Active substance: Foscarnet sodium hexahydrate, equivalent to 24 mg foscarnet sodium per ml. Foscarnet sodium (chemical name: trisodium phosphonoformate hexahydrate; molecular formula: Na₃CO₅P·6H₂O) is a white crystalline powder that is freely soluble in water. The molecular weight of the hexahydrate is 300.04 g/mol.
• Other ingredient: Water for injections (aqua ad iniectabilia).

The solution has a pH of approximately 7.4 (range 6.8–8.0) and an osmolality of approximately 320 mOsm/kg, making it near-isotonic. The solution appears clear and colourless to slightly yellowish.

Foscarnet Tillomed is available in glass bottles or vials containing 250 ml or 500 ml of the 24 mg/ml solution for infusion. Each 250 ml bottle contains 6,000 mg (6 g) of foscarnet sodium, and each 500 ml bottle contains 12,000 mg (12 g) of foscarnet sodium. Not all pack sizes may be marketed in your country.

For patients requiring peripheral venous administration, the 24 mg/ml solution should be diluted with an equal volume of glucose 5% solution or sodium chloride 0.9% solution to achieve a final concentration of 12 mg/ml, which is better tolerated by peripheral veins. For central venous administration, the undiluted 24 mg/ml solution may be used.

The marketing authorisation holder is Tillomed Laboratories Ltd. Foscarnet was originally developed and marketed under the brand name Foscavir by AstraZeneca (now marketed by Clinigen in some countries). Foscarnet Tillomed is a generic equivalent product meeting the same pharmaceutical quality standards as the originator.