February 27, 2017
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Foscavir

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Foscavir




Side Effects
Interactions

SIDE EFFECTS

THE MAJOR TOXICITY OF FOSCAVIR IS RENAL IMPAIRMENT (see WARNINGS). Approximately 33% of 189 patients with AIDS and CMV retinitis who received FOSCAVIR (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 normal saline or 5% dextrose solution was given with each infusion of FOSCAVIR was 12% (34/280).

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

FOSCAVIR treatment was associated with seizures in 18/189 (10%) AIDS patients in the initial five controlled studies (see WARNINGS). 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 FOSCAVIR (see OVERDOSE).

In five controlled U.S. clinical trials the most frequently reported adverse events in patients with AIDS and CMV retinitis are shown in Table 9. These figures were calculated without reference to drug relationship or severity.

TABLE 9 Adverse Events Reported in Five Controlled US Clinical Trials

  n = 189   n = 189
Fever 65% Abnormal Renal Function 27%
Nausea 47% Vomiting 26%
Anemia 33% Headache 26%
Diarrhea 30% Seizures 10%

From the same controlled studies, adverse events categorized by investigator as “severe” are shown in Table 10. Although death was specifically attributed to FOSCAVIR in only one case, other complications of FOSCAVIR (i.e., renal impairment, electrolyte abnormalities, and seizures) may have contributed to patient deaths (see WARNINGS).

TABLE 10 Severe Adverse Events

  n = 189
Death 14%
Abnormal Renal Function 14%
Marrow Suppression 10%
Anemia 9%
Seizures 7%

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

Incidence Of 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 (see WARNINGS)

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

Hematologic: anemia, granulocytopenia, leukopenia, neutropenia (see PRECAUTIONS)

Metabolic and Nutritional: mineral and electrolyte imbalances (see WARNINGS) 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 (see WARNINGS)

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 (see WARNINGS)

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

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

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, maculopapular 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 FOSCAVIR 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 11 (see Clinical Trials).

TABLE 11 FGRCT: Selected Adverse Events*

EVENT GANCICLOVIR FOSCARNET
No. of Events No. of Patients Rates No. of Events No. of Patients Rates
Absolute neutrophil count decreasing to <0.50 x 109 per liter 63 41 1.30 31 17 0.72
Serum creatinine increasing to >260 μmol per liter (>2.9 mg/dL) 6 4 0.12 13 9 0.30
Seizure 21 13 0.37 19 13 0.37
Catheterization-related infection 49 27 1.26 51 28 1.46
Hospitalization 209 91 4.74 202 75 5.03
* Values for the treatment groups refer only to patients who completed at least one follow-up visit – i.e., 133 to 119 patientsin the ganciclovir group and 93 to 100 in the foscarnet group. “Events” denotes all events observed and “patients” the numberof 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 FOSCAVIR or ganciclovir monotherapy are shown in Table 12. The most common reason for a treatment change in patients assigned to either FOSCAVIR or ganciclovir was retinitis progression. The most frequent reason for a treatment change in the combination treatment group was toxicity.

TABLE 12 CRRT: Selected Adverse Events

  Foscavir
N=88
Ganciclovir
N=93
Combination
N=93
No. Events No. Pts.* Rate No. Events No. Pts.* Rate No. Events No. Pts.* Rate
Anemia (Hgb <70g/L) 11 7 0.20 9 7 0.14 19 15 0.33
Neutropenia                  
  ANC <0.75 x 109 cells/L 86 32 1.53 95 41 1.51 107 51 1.91
  ANC <0.50 x 109 cells/L 50 25 0.91 49 28 0.80 50 28 0.85
Thrombocytopenia                  
  Platelets <50 x 109/L 28 14 0.50 19 8 0.43 40 15 0.56
  Platelets <20 x 109/L 1 1 0.01 6 2 0.05 7 6 0.18
Nephrotoxicity                  
Creatinine >260 μmol/L (>2.9 mg/dL) 9 7 0.15 10 7 0.17 11 10 0.20
Seizures 6 6 0.17 7 6 0.15 10 5 0.18
Hospitalizations 86 53 1.86 111 59 2.36 118 64 2.36
* Pts. = patients with event; †Rate = events/person/year; ‡ANC = absolute neutrophil count

Adverse events that have been reported in post-marketing surveillance include: status epilepticus, ventricular arrhythmia, prolongation of QT interval, torsade de pointes, gamma GT increased, diabetes insipidus (usually nephrogenic), renal calculus, Fanconi syndrome acquired, renal tubular acidosis, renal tubular necrosis, crystal-induced nephropathy, hypercalcemia, hypernatremia, esophageal ulceration 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.

Read the Foscavir (foscarnet sodium injection) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

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 hypocalcemia; one patient died with severe hypocalcemia. Toxicity associated with concomitant use of aerosolized pentamidine has not been reported. Because FOSCAVIR can reduce serum levels of ionized calcium, extreme caution is advised when used concurrently with other drugs known to influence serum calcium levels (e.g., intravenous pentamidine). Renal impairment and symptomatic hypocalcemia have been observed during concurrent treatment with FOSCAVIR and intravenous pentamidine.

Because of foscarnet’s tendency to cause renal impairment, the use of FOSCAVIR should be avoided in combination with potentially nephrotoxic drugs such as aminoglycosides, amphotericin B, cyclosporine, acyclovir, methotrexate, tacrolimus and intravenous pentamidine (see above) unless the potential benefits outweigh the risks to the patient.

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.

Abnormal renal function has been observed in clinical practice during the use of FOSCAVIR and ritonavir, or FOSCAVIR, ritonavir, and saquinavir. (See DOSAGE AND ADMINISTRATION.)

Read the Foscavir Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 11/28/2016

Side Effects
Interactions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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