Foscarnet Side Effects

Brand Names: Foscavir

Please note - some side effects for Foscarnet may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Foscarnet - for the Consumer

Foscarnet

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Foscarnet:

Anxiety; appetite loss; chills; confusion; decreased sensitivity to touch; depression; fatigue; general body discomfort; headache; involuntary muscle movements; joint pain; nausea; pain; rigid muscles; stomach pain; sweating; vision problems.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal skin sensations; cough; decreased urination; diarrhea; dizziness; fainting; fast heartbeat; genital ulcers or irritation; infection (fever, chills, sore throat); irregular heartbeat; numbness in hands, arms, legs, and feet; pain or redness at the injection site; rectal bleeding; seizures; tingling in fingers or around the mouth; unusual tiredness or weakness; urination problems; vomiting.

Foscarnet Side Effects - for the Professional

Foscarnet

THE MAJOR TOXICITY OF Foscarnet SODIUM IS RENAL IMPAIRMENT. Approximately 33% of 189 patients with AIDS and CMV retinitis who received Foscarnet sodium (60 mg/kg TID), without adequate hydration, developed significant impairment of renal function (serum creatinine≥ 2.0 mg/dL). The incidence of renal impairment in subsequent clinical trials in which 1000 mL of 0.9% sodium chloride injection or 5% dextrose solution was given with each infusion of Foscarnet sodium was 12% (34/280).

Foscarnet sodium has been associated with changes in serum electrolytes including hypocalcemia (15 to 30%), hypophosphatemia (8 to 26%) and hyperphosphatemia (6%), hypomagnesemia (15 to 30%), and hypokalemia (16 to 48%). The higher percentages were derived from those patients receiving hydration.

Foscarnet sodium treatment was associated with seizures in 18/189 (10%) AIDS patients in the initial five controlled studies. Risk factors associated with seizures included impaired baseline renal function, low total serum calcium, and underlying CNS conditions predisposing the patient to seizures. The rate of seizures did not increase with duration of treatment. Three cases were associated with overdoses of Foscarnet sodium.

In five controlled U.S. clinical trials the most frequently reported adverse events in patients with AIDS and CMV retinitis are shown in Table 5. These figures were calculated without reference to drug relationship or severity.

From the same controlled studies, adverse events categorized by investigator as “severe” are shown in Table 6. Although death was specifically attributed to Foscarnet sodium injection in only one case, other complications of Foscarnet sodium (i.e., renal impairment, electrolyte abnormalities, and seizures) may have contributed to patient deaths.

From the five initial U.S. controlled trials of Foscarnet sodium injection, the following list of adverse events has been compiled regardless of causal relationship to Foscarnet sodium. Evaluation of these reports was difficult because of the diverse manifestations of the underlying disease and because most patients received numerous concomitant medications.

Incidence 5% or Greater

Body as a Whole: fever, fatigue, rigors, asthenia, malaise, pain, infection, sepsis, death

Central and Peripheral Nervous System: headache, paresthesia, dizziness, involuntary muscle contractions, hypoesthesia, neuropathy, seizures including grand mal seizures

Gastrointestinal System: anorexia, nausea, diarrhea, vomiting, abdominal pain

Hematologic:anemia, granulocytopenia, leukopenia

Metabolic and Nutritional: mineral and electrolyte imbalances including hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia, hyperphosphatemia

Psychiatric: depression, confusion, anxiety

Respiratory System: coughing, dyspnea

Skin and Appendages: rash, increased sweating

Urinary: alterations in renal function including increased serum creatinine, decreased creatinine clearance, and abnormal renal function

Special Senses: vision abnormalities

Incidence between 1% and 5%

Application Site: injection site pain, injection site inflammation

Body as a Whole: back pain, chest pain, edema, influenza-like symptoms, bacterial infections, moniliasis, fungal infections, abscess

Cardiovascular: hypertension, palpitations, ECG abnormalities including sinus tachycardia, first degree AV block and non-specific ST-T segment changes, hypotension, flushing, cerebrovascular disorder

Central and Peripheral Nervous System: tremor, ataxia, dementia, stupor, generalized spasms, sensory disturbances, meningitis, aphasia, abnormal coordination, leg cramps, EEG abnormalities

Gastrointestinal: constipation, dysphagia, dyspepsia, rectal hemorrhage, dry mouth, melena, flatulence, ulcerative stomatitis, pancreatitis

Hematologic: thrombocytopenia, platelet abnormalities, thrombosis, white blood cell abnormalities, lymphadenopathy

Liver and Biliary: abnormal A-G ratio, abnormal hepatic function, increased SGPT, increased SGOT

Metabolic and Nutritional: hyponatremia, decreased weight, increased alkaline phosphatase, increased LDH, increased BUN, acidosis, cachexia, thirst, hypocalcemia

Musculo-Skeletal: arthralgia, myalgia

Neoplasms: lymphoma-like disorder, sarcoma

Psychiatric: insomnia, somnolence, nervousness, amnesia, agitation, aggressive reaction, hallucination

Respiratory System: pneumonia, sinusitis, pharyngitis, rhinitis, respiratory disorders, respiratory insufficiency, pulmonary infiltration, stridor, pneumothorax, hemoptysis, bronchospasm

Skin and Appendages: pruritus, skin ulceration, seborrhea, erythematous rash, maculo-papular rash, skin discoloration

Special Senses: taste perversions, eye abnormalities, eye pain, conjunctivitis

Urinary System: albuminuria, dysuria, polyuria, urethral disorder, urinary retention, urinary tract infections, acute renal failure, nocturia, facial edema

Selected adverse events occurring at a rate of less than 1% in the five initial U.S. controlled clinical trials of Foscarnet sodium include: syndrome of inappropriate antidiuretic hormone secretion, pancytopenia, hematuria, dehydration, hypoproteinemia, increases in amylase and creatinine phosphokinase, cardiac arrest, coma, and other cardiovascular and neurologic complications.

Selected adverse event data from the Foscarnet vs. Ganciclovir CMV Retinitis Trial (FGCRT), performed by the Studies of the Ocular Complications of AIDS (SOCA) Research Group, are shown in Table 7.

* Values for the treatment groups refer only to patients who completed at least one follow-up visit − i.e., 113 to 119 patients in the ganciclovir group and 93 to 100 in the Foscarnet group. “Events” denotes all events observed and “patients” the number of patients with one or more of the indicated events.

†Per person-year at risk

‡ Final frozen SOCA I database dated October 1991.

Selected adverse events from ACTG Study 228 (CRRT) comparing combination therapy with Foscarnet sodium injection or ganciclovir monotherapy are shown in Table 8. The most common reason for a treatment change in patients assigned to either Foscarnet sodium injection or ganciclovir was retinitis progression. The most frequent reason for a treatment change in the combination treatment group was toxicity.

* Pts. = patients with event; †Rate = events/person/year;‡ANC = absolute neutrophil count

Adverse events that have been reported in post-marketing surveillance include: ventricular arrhythmia, prolongation of QT interval, gamma GT increased, diabetes insipidus (usually nephrogenic), renal calculus, and muscle disorders including myopathy, myositis, muscle weakness and rare cases of rhabdomyolysis. Cases of vesiculobullous eruptions including erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson Syndrome have been reported. In most cases, patients were taking other medications that have been associated with toxic epidermal necrolysis or Stevens-Johnson Syndrome.

Side Effects by Body System

General

Renal impairment is the major toxicity of foscarnet. The most frequent adverse events reported during clinical trials included fever (65%), nausea (47%), anemia (33%), diarrhea (30%), abnormal renal function (27%), vomiting (26%), headache (26%), and seizures (10%). Adverse events classified as severe included death (14%), abnormal renal function (14%), bone marrow suppression (10%), anemia (9%), and seizures (7%).

Renal

Renal side effects have included dose-related renal impairment, which is the major toxicity of foscarnet and has occurred in up to 33% of patients. Acute renal failure, serum creatinine elevations greater than or equal to 2.9 mg/dL, renal tubular acidosis, and renal calculi have also been reported.

Renal adverse effects are due to acute tubular necrosis, possibly from deposition of foscarnet crystals in the renal tubules and capillaries. Renal failure as well as tubular dysfunction such as nephrogenic diabetes insipidus may result. The development of nephrotoxicity was most common during the third week of therapy in one study.

Nephrotoxicity is reversible in patients with previously adequate renal function. Hydration with 2.5 liters of normal saline per day beginning the day before foscarnet therapy has been shown to decrease the incidence of nephrotoxicity.

Gastrointestinal

Gastrointestinal side effects have included nausea (47%), vomiting (26%), diarrhea (30%), anorexia (5% or more), and abdominal pain (5% or more). Constipation, dysphagia, dyspepsia, rectal hemorrhage, dry mouth, melena, flatulence, ulcerative stomatitis, and pancreatitis have been reported in 1% to 5% of patients. An isolated case of uvula and esophageal ulceration has been reported.

Hematologic

Hematologic side effects have included anemia (33%), neutropenia (17%), granulocytopenia (5% or more), and leukopenia (5% or more). Thrombocytopenia, platelet abnormalities, thrombosis, blood cell abnormalities, and lymphadenopathy have been reported in 1% to 5% of patients.

Nervous system

Nervous system side effects have included headache (26%) and seizures (10%). Paresthesia, dizziness, involuntary muscle contractions, hypoesthesia, neuropathy, and grand mal seizures have been reported in greater than or equal to 5% of patients. Tremor, ataxia, dementia, stupor, generalized spasms, sensory disturbances, meningitis, aphasia, abnormal coordination, leg cramps, and EEG abnormalities have been reported in 1% to 5% of patients. Risk factors for foscarnet-related seizures include low neutrophil count, central nervous system disease, impaired renal function, and electrolyte and metabolic abnormalities.

Metabolic

Metabolic disturbances have occurred in 15% to 40% of patients treated with foscarnet and include hypocalcemia, hypomagnesemia, hypokalemia, hyponatremia secondary to nephrogenic diabetes insipidus, and hypo- and hyperphosphatemia. More severe metabolic abnormalities have resulted in tremors, twitches, arrhythmias, parenthesis, and seizures. Dehydration, hypoproteinemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and increased amylase and creatinine phosphokinase have been reported in less than 1% of patients. Hypercalcemia has also been reported.

Serum ionized calcium concentrations have been shown to decrease acutely in a dose-dependent manner following an infusion of foscarnet. Total calcium and phosphate levels were not significantly affected. Foscarnet is believed to complex with ionized calcium.

Other

Other side effects have included fever (65%), and fatigue, rigors, asthenia, malaise, pain, infection, and sepsis in greater than or equal to 5% of patients.

Local

Local side effects have included injection site pain and inflammation.

Dermatologic

Dermatologic side effects have included rash and increased sweating in greater than or equal to 5% of patients. Pruritus, skin ulceration, seborrhea, erythematous rash, maculopapular rash, and skin discoloration have been reported in 1% to 5% of patients. Erythema multiforme, toxic epidermal necrolysis, eosinophilic folliculitis, and Stevens-Johnson syndrome have been reported during postmarketing experience.

Cardiovascular

Cardiovascular side effects have included hypertension, palpitations, ECG abnormalities, sinus tachycardia, first degree AV block, nonspecific ST-T segment changes, hypotension, flushing, cerebrovascular disorder in 1% to 5% of patients. Cardiac arrest, coma, and other cardiovascular complications have been reported in less than 1% of patients.

Reversible cardiac dysfunction has been reported in one patient receiving foscarnet, who experienced shortness of breath, increased heart rate, and pulmonary edema, which reoccurred upon rechallenge. Serum electrolytes were within normal limits. Ventricular arrhythmia and QT interval prolongation have been reported during postmarketing experience.

Hepatic

Hepatic side effects have included abnormal hepatic function, abnormal A-G ratio, increased SGPT, and increased SGOT in 1% to 5% of patients. Increased gamma glutamyl transpeptidase has been reported during postmarketing experience.

Musculoskeletal

Musculoskeletal side effects have included arthralgia and myalgia in 1% to 5% of patients. Myopathy, myositis, muscle weakness, and rhabdomyolysis have been reported during postmarketing experience.

Oncologic

Oncologic side effects have included lymphoma-like disorder and sarcoma in 1% to 5% of patients.

Respiratory

Respiratory side effects have included coughing and dyspnea in greater than or equal to 5% of patients. Pneumonia, sinusitis, pharyngitis, rhinitis, respiratory disorders, respiratory insufficiency, pulmonary infiltration, stridor, pneumothorax, hemoptysis, and bronchospasm have been reported in 1% to 5% of patients.

Psychiatric

Psychiatric side effects have included confusion and anxiety in greater than or equal to 5% of patients. Insomnia, somnolence, nervousness, amnesia, agitation, aggressive reaction, and hallucination have been reported in 1% to 5% of patients.

Ocular

Ocular side effects have included eye abnormalities, eye pain, and conjunctivitis in 1% to 5% of patients.

Genitourinary

Penile ulcerations have been reported to occur after a median of 11 days of induction therapy and 30 days of maintenance therapy, and heal within six days of drug discontinuation. Ulceration has been reported more often in uncircumcised patients. Vulvar erosion may also occur but is less common. Penile ulceration is thought to result from local irritation by high concentrations of foscarnet in the urine. Good hygiene may help reduce irritation.

Genitourinary side effects have included albuminuria, dysuria, polyuria, urethral disorder, urinary retention, urinary tract infections, and nocturia in 1% to 5% of patients, and hematuria in less than 1% of patients. Local irritation and ulceration of penile epithelium in male patients and vulvovaginal ulceration in a female patient have also been reported.

Other

Foscarnet accumulates in teeth and bones of growing animals. Tooth enamel development has been affected in rats receiving foscarnet.

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