Foscarnet

126.004

126.01

364P9RVW4X

DTXSID0048478

C71630

J05AD01|J - Antiinfectives for systemic use

94.8

-2.1

Solid

88.06 °C

Completely soluble in water.

Store at 20 to 25 deg C (68 to 77 deg F). Protect from excessive heat (above 40 deg C) and from freezing.

1.62X10-6 mm Hg at 25 deg C (est)

Henry's Law constant = 2.01X10-15 atm-cu m/mol at 25 °C (est)

pKa = 3.13 (est)

Hexahydrate, mp >250 °C/Foscarnet sodium/|Hydroxyl radical reaction rate constant = 8.0X10-13 cu cm/molec-sec at 25 °C (est)

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Other drugs and supplements can be administered to a patient receiving foscarnet sodium. However, care must be taken to ensure that foscarnet sodium is only administered with 0.9% sodium chloride injection or 5% dextrose solution and that no other drug or supplement is administered concurrently via the same catheter.|Foscarnet has been reported to be chemically incompatible with 30% dextrose, amphotericin B, and solutions containing calcium such as Ringer's lactate and TPN.|Physical incompatibility with other IV drugs has also been reported including acyclovir sodium, ganciclovir, trimetrexate glucuronate, pentamidine isethionate, vancomycin, trimethoprim/sulfamethoxazole, diazepam, midazolam, digoxin, phenytoin, leucovorin, and prochlorperazine. Because of foscarnet's chelating properties, a precipitate can potentially occur when divalent cations are administered concurrently in the same catheter.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including foscarnet sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Foscarnet sodium/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Accidental skin and eye contact with foscarnet sodium solution may cause local irritation and burning sensation.

Antiviral drugs have been recently recognized as one of the emerging contaminants in the environment. These are discharged after therapeutic use through human excretion. Effluent containing high concentration of antiviral drugs discharged from production facilities is also a cause of concern to nearby aquatic bodies. There is an increased interest in their removal because they are highly bioactive. Some antiviral drugs are resistant to conventional methods of degradation, and there is a risk of development of antiviral resistance in humans and animals if exposed repeatedly for long periods. To date, the potential human, animal, and ecological risks associated with the discharge of these antiviral compounds to the environment are not well documented. This study presents a brief summary on occurrence, ecotoxicological risks, and physicochemical properties of antiviral drugs in the environment. The needs regarding removal, disposal, and treatment of antiviral drugs are also addressed(1). /Antiviral drugs/

Oral, rat LD50: >2,000 mg/kg. Signs of overdose include renal impairment.

Intravenous foscarnet therapy is associated with mild-to-moderate serum ALT elevations in a proportion of patients, but the drug is usually given to patients with multiorgan disease and conditions that may be associated with some degree of hepatic injury. The ALT elevations are usually asymptomatic and resolve even with continuation of foscarnet. Single case reports of clinically apparent liver injury that were possibly attributable to foscarnet have been reported. The pattern of injury was cholestatic arising within weeks of starting foscarnet but the clinical features of the liver injury have not been described in any detail.

Concomitant administration of foscarnet and parenteral pentamidine has been associated with hypocalcemia, including severe hypocalcemia resulting in death. Toxicity associated with concomitant administration of foscarnet and orally inhaled pentamidine has not been reported to date.|Abnormal renal function has occurred in patients receiving foscarnet in combination with ritonavir and/or saquinavir.|To report a possible interaction between foscarnet and ciprofloxacin in two patients with AIDS, cytomegalovirus (CMV) retinitis, and disseminated Mycobacterium avium complex (MAC) infection and to review the available literature related to foscarnet-associated seizures. Case report information was obtained from Medical Service Daily Rounds during the patients' hospitalization and from the patients' medical records. Computerized (MEDLINE) and manual (Index Medicus) search methods were used to obtain English-language literature published between 1980 and 1993.Foscarnet is a synthetic antiviral agent with activity against herpesviruses and HIV. The incidence of seizures with foscarnet infusion is high, ranging from 13 to 15 percent. Predisposing factors such as renal impairment, electrolyte and metabolic abnormalities, and underlying neurologic disorders have been associated with seizures during foscarnet therapy. We describe two patients with AIDS who developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of CMV retinitis and disseminated MAC infection, respectively. Neither of the patients had any of the aforementioned risk factors for foscarnet-associated seizures. Concurrent administration of ciprofloxacin, a known epileptogenic agent, and foscarnet may predispose patients to the development of seizures.

14-17%

Foscarnet's production and administration as an antiviral(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that foscaranet is expected to have moderate mobility in soil(SRC). The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form in the environment. Anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a anion and anions do not volatilize. Foscarnet is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that foscarnet is expected to adsorb to suspended solids and sediment(SRC). The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -1.93(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), foscarnet, which has an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase foscarnet is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 13 days(SRC), calculated from its rate constant of 8.0X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase foscarnet may be removed from the air by wet and dry deposition(SRC). Foscarnet does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of foscarnet with photochemically-produced hydroxyl radicals has been estimated as 8.0X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Foscarnet is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Foscarnet does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for foscarnet(SRC), using an estimated log Kow of -1.93(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of foscarnet can be estimated to be 330(SRC). According to a classification scheme(2), this estimated Koc value suggests that foscarnet is expected to have moderate mobility in soil. The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The estimated pKa of 3.13(1) indicates foscarnet will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). Foscarnet is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg(SRC), determined from a fragment constant method(2).

It is not known whether foscarnet sodium is excreted in human milk; however, in lactating rats administered 75 mg/kg, foscarnet sodium was excreted in maternal milk at concentrations three times higher than peak maternal blood concentrations.

Occupational exposure to foscarnet may occur through inhalation and dermal contact with this compound at workplaces where foscarnet is produced or used. Exposure to foscarnet among the general population may be limited to those administered the drug. (SRC)

For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and for treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.|FDA Label

Foscarnet a simple pyrophosphate molecule which has antiviral activity against many viruses and is used intravenously in therapy of serious cytomegalovirus infections, largely in immunocompromised patients. Foscarnet has been associated with mild-to-moderate serum aminotransferase elevations during intravenous therapy, but not with episodes of clinically apparent liver injury.

Antiviral Agents

Antiviral Agents; Reverse Transcriptase Inhibitors|Foscarnet sodium injection is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. /Included in US product label/|Foscarnet sodium injection is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Combination therapy with foscarnet sodium and ganciclovir is indicated for patients who have relapsed after monotherapy with either drug. /Included in US product label/

/BOXED WARNING/ Renal impairment is the major toxicity of foscarnet sodium injection. Frequent monitoring of serum creatinine, with dose adjustment for changes in renal function, and adequate hydration with administration of foscarnet sodium injection, is imperative.|/BOXED WARNING/ Seizures, related to alterations in plasma minerals and electrolytes, have been associated with foscarnet sodium injection treatment. Therefore, patients must be carefully monitored for such changes and their potential sequelae. Mineral and electrolyte supplementation may be required.|/BOXED WARNING/ Foscarnet sodium injection is indicated for use only in immunocompromised patients with CMV retinitis and mucocutaneous acyclovir-resistant HSV infections.|Foscarnet sodium injection is contraindicated in patients with clinically significant hypersensitivity to foscarnet sodium.|For more Drug Warnings (Complete) data for Foscarnet (31 total), please visit the HSDB record page.

Strains of both HSV and CMV that are resistant to foscarnet sodium can be readily selected in vitro by passage of wild type virus in the presence of increasing concentrations of the drug. All foscarnet sodium resistant mutants are known to be generated through mutation in the viral DNA polymerase gene. CMV strains with double mutations conferring resistance to both foscarnet sodium and ganciclovir have been isolated from patients with AIDS. The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy.

Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.

Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)|Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)

Poorly absorbed after oral administration (bioavailability from 12 to 22%).|2.13 +/- 0.71 mL/min/kg [patients had normal renal function (CrCl > 80 mL/min]|The pharmacokinetics, absolute bioavailability, /and/ accumulation over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function. Peak plasma drug concentrations were (mean +/- standard deviation) 46.4 +/- 10.8 uM (90 mg/kg QD), 45.7 +/- 6.9 uM (90 mg/ kg BID), and 64.9 +/- 31.7 uM (180 mg/kg QD) on day 1 and rose to 86.2 +/- 35.8, 78.7 +/- 35.2, and 86.4 +/- 25.0 uM, respectively, on day 8. The mean peak concentration in plasma following the intravenous administration of foscarnet (90 mg/kg) was 887.3 +/- 102.7 uM (n = 13). The terminal half-life in plasma remained unchanged, averaging 5.5 +/- 2.2 hr on day 1 (n = 15) and 6.6 +/- 1.9 hr on day 8 (n = 13), whereas it was 5.7 +/- 0.7 hr following intravenous dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7% (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively. The overall 24-hr urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day 1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous dosing. The glomerular filtration rate and creatinine clearance remained constant, and the mean 24-hr renal clearances of foscarnet for the entire study group were 96 +/- 18 mL/min (day 1), 88 +/- 13 mL/min (day 8), and 103 +/- 16 mL/min after intravenous dosing.|Six patients with human immunodeficiency virus were given foscarnet in oral solution, 4000 mg every 6 hours for 3 days, followed by a washout period for 2 days and continuous intravenous infusion of 16,000 mg/24 hr over 72 hours. After oral foscarnet, plasma concentrations were less than 33 mumol/L in four patients; two had occasional concentrations of 35 to 50 mumol/L. The extent of absorption varied between 12% and 22%. During intravenous infusion, plasma concentrations ranged between 75 and 265 mumol/L. The disposition of foscarnet was triphasic, with mean half-lives of 0.45, 3.3, and 18 hours. Excretion data suggested elimination was by tubular secretion and glomerular filtration. Renal clearance was 176 mL/min 1.73 sq m. The apparent nonrenal clearance, 40 mL/min 1.73 sq m, probably reflects sequestration of foscarnet into bone. Ten percent to 28% of the cumulative dose may have been deposited in bone 2 days after infusion. A slight increase in serum calcium levels and changes in serum phosphate values may reflect the uptake of foscarnet in bone. Five patients had diarrhea (oral) and two had thrombophlebitis (intravenous).|It is not known whether foscarnet sodium is excreted in human milk...

Not metabolized.

3.3-6.8 hours|...The foscarnet half-lives during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD).were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively. ...|The pharmacokinetics, absolute bioavailability, /and/ accumulation over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function ... The terminal half-life in plasma remained unchanged, averaging 5.5 +/- 2.2 hr on day 1 (n = 15) and 6.6 +/- 1.9 hr on day 8 (n = 13), whereas it was 5.7 +/- 0.7 hr following intravenous dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7% (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively. The overall 24-hr urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day 1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous dosing.

Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.|Foscarnet sodium is an organic analogue of inorganic pyrophosphate that inhibits replication of herpesviruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet sodium exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Foscarnet sodium does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet sodium. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet sodium and may not respond to therapy with foscarnet sodium. The combination of foscarnet sodium and ganciclovir has been shown to have enhanced activity in vitro.|The pyrophosphate (PP(i)) analog foscarnet inhibits viral DNA-polymerases and is used to treat cytomegalovirus and human immunodeficiency vius infections. Nucleotide cyclases and DNA-polymerases catalyze analogous reactions, i.e. a phosphodiester bond formation, and have similar topologies in their active sites. Inhibition by foscarnet of adenylyl cyclase isoforms was therefore tested with (i) purified catalytic domains C1 and C2 of types I and VII (IC1 and VIIC1) and of type II (IIC2) and (ii) membrane-bound holoenzymes (from mammalian tissues and types I, II, and V heterologously expressed in Sf9 cell membranes). Foscarnet was more potent than PP(i) in suppressing forskolin-stimulated catalysis by both, IC1/IIC2 and VIIC1/IIC2. Stimulation of VIIC1/IIC2 by Galpha(s) relieved the inhibition by foscarnet but not that by PP(i). The IC(50) of foscarnet on membrane-bound adenylyl cyclases also depended on their mode of regulation. These findings predict that receptor-dependent cAMP formation is sensitive to inhibition by foscarnet in some, but not all, cells. This was verified with two cell lines; foscarnet blocked cAMP accumulation after A(2A)-adenosine receptor stimulation in PC12 but not in HEK-A(2A) cells. Foscarnet also inhibited soluble and, to a lesser extent, particulate guanylyl cylase. Thus, foscarnet interferes with the generation of cyclic nucleotides, an effect which may give rise to clinical side effects. The extent of inhibition varies with the enzyme isoform and with the regulatory input.

There is no specific antidote for foscarnet sodium overdose. Hemodialysis and hydration may be of benefit in reducing drug plasma levels in patients who receive an overdosage of foscarnet sodium, but the effectiveness of these interventions has not been evaluated. The patient should be observed for signs and symptoms of renal impairment and electrolyte imbalance. Medical treatment should be instituted if clinically warranted.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for Foscarnet (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ The literature has been reviewed for contact dermatitis from topical antiviral drugs. 15 agents have been identified including acyclovir, imiquimod, podophyllin, podofilox, cidofovir, penciclovir, vidarabine, idoxuridine, trifluridine, tromantadine, lamivudine, interferon intralesional injections and ophthalmic solution, fomivirsen and foscarnet intravitreal injections and ganciclovir intraocular implants. Patch testing has been documented in certain individuals and cross-sensitization has been observed to contribute significantly to some allergic reactions.|/SIGNS AND SYMPTOMS/ In controlled clinical trials performed in the United States, overdosage with foscarnet sodium injection was reported in 10 out of 189 patients. All 10 patients experienced adverse events and all except one made a complete recovery. One patient died after receiving a total daily dose of 12.5 g for three days instead of the intended 10.9 g. The patient suffered a grand mal seizure and became comatose. Three days later the patient expired with the cause of death listed as respiratory/cardiac arrest. The other nine patients received doses ranging from 1.14 times to 8 times their recommended doses with an average of 4 times their recommended doses. Overall, three patients had seizures, three patients had renal function impairment, four patients had paresthesias either in limbs or periorally, and five patients had documented electrolyte disturbances primarily involving calcium and phosphate.|/CASE REPORTS/ Foscarnet (FC) is a new antiviral agent which has been recently proposed for the treatment of severe cytomegalovirus (CMV) infections in immunocompromised patients. When used intravenously (i.v.), main adverse effects of FC are a fall in hemoglobin, and an increase in liver enzymes and serum calcium. Although increased serum creatinine has been noted in several patients, deterioration of renal function is often accounted for by the concomitant use of other nephrotoxic drugs, the severity of underlying disease or the presence of graft rejection. Consequently FC is often considered as a non or poorly nephrotoxic drug. We report 4 cases of acute renal failure (ARF) which can be exclusively attributed to FC. FC was used for CMV chorioretinitis in 3 AIDS patients and in one non-immunocompromised patient. ARF was diagnosed between the 6th and 15th day of treatment, with oligoanuria in two patients (one of whom required two hemodialysis periods). ARF was most likely secondary to acute toxic tubulopathy. Three patients did not receive any other nephrotoxic drug. The fourth patient received concomitantly sulfadiazine but renal function returned to baseline value after FC completion although sulfadiazine was continued. In conclusion, our 4 observations suggest that FC may be responsible for acute tubulopathy.|/CASE REPORTS/ A case of fixed drug eruption (FDE) secondary to foscarnet is reported. This drug has recently become available on a compassionate use basis for treatment of cytomegalovirus (CMV) infection which may cause significant disease in immunosuppressed patients. Foscarnet provides a useful alternative to the only licensed anti-CMV drug currently available, namely ganciclovir (DHPG), as it has a different toxicity profile. In particular, it does not appear to cause bone marrow suppression which is of importance in AIDS patients as many of them are taking concurrent zidovudine.|For more Human Toxicity Excerpts (Complete) data for Foscarnet (11 total), please visit the HSDB record page.

Foscarnet

Each milliliter of foscarnet sodium injection contains 24 mg of foscarnet sodium hexahydrate in Water for Injection, USP. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. /Available in/ 500 or 250 mL bottles.|Foscavir