Vepesid 50 mg

High dose cyclosporine, resulting in concentrations above 2000 ng/mL, administered with oral etoposide has led to an 80% increase in etoposide exposure (AUC) with a 38% decrease in total body clearance of etoposide compared to etoposide alone. Severe cases of neuropathy have been reported in 0.7% of patients possibly due to an interaction of vincristine and VEPESID.

Safety and effectiveness in pediatric patients have not been systematically studied. Clinical experience in childhood malignancies is very limited (see Warnings).

Carcinogenicity tests with VEPESID have not been conducted in laboratory animals. Given its mechanism of action, it should be considered a possible carcinogen in humans.

The occurrence of acute leukemia, which can occur with or without a preleukemic phase, has been reported rarely in patients treated with VEPESID in association with other antineoplastic drugs. Neither the cumulative risk, nor the predisposing factors related to the development of secondary leukemia are known. The roles of both administration schedules and cumulative doses of etoposide have been suggested, but have not been clearly defined.

An 11q23 chromosome abnormality has been observed in some cases of secondary leukemia in patients who have received epipodophyllotoxins. This abnormality has also been seen in patients developing secondary leukemia after being treated with chemotherapy regimens not containing epipodophyllotoxins and in leukemia occurring de novo. Another characteristic that has been associated with secondary leukemia in patients who have received epipodophyllotoxins appears to be a short latency period, with average median time to development of leukemia being approximately 32 months.

The physician must evaluate the need and usefulness of the drug against the risk of adverse reactions. Most such adverse reactions are reversible if detected early. If severe reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of VEPESID (etoposide) therapy should be carried out with caution, and with adequate consideration of the further need for the drug and alertness to the possible recurrence of toxicity. Patients with low serum albumin may be at increased risk for etoposide-associated toxicities.

VEPESID should be administered by individuals experienced in the use of antineoplastic therapy.

Myelosuppression is dose related and dose limiting, with granulocyte nadirs occurring 7 to 14 days and platelet nadirs occurring 9 to 16 days after drug administration. Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported.

Liver and renal function should be regularly monitored.

Professional staff administering VEPESID should exercise particular care to prevent spillage and self-contact with the drug. Skin reactions, at times severe, associated with accidental exposure to VEPESID may occur. Gloves should be worn by anyone handling the drug.

There has been evidence of VEPESID being excreted in human milk.

Because of the potential for serious adverse reactions in nursing infants from etoposide, breast-feeding should be discontinued.

As with any potent antineoplastic drug, the benefit to patient versus the risk of toxicity must be carefully weighed.

VEPESID can cause fetal harm when administered to pregnant women.

VEPESID has been shown to be embryotoxic in rats and teratogenic in mice and rats. There are no adequate and well-controlled studies in pregnant women. If the drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant and should exercise adequate contraceptive control.

VEPESID has caused reduced or absent spermatogenesis and reduced testes weights at autopsy in rats and dogs, as well as reduced weight of ovaries in female rats. Chronic toxicity studies in rats have shown etoposide to have an oncogenic potential (see Adverse Effects, Hematologic Toxicity).

Reversible alopecia, sometimes progressing to total baldness was observed in up to 66% of patients.

Since leukopenia and thrombocytopenia have been reported in patients on VEPESID (etoposide) therapy, platelets and white blood cell counts should be performed prior to each cycle (see Warnings).

Myelosuppression with fatal outcome has been reported following etoposide administration (see Warnings and Precautions).

The occurrence of acute leukemia with or without a preleukemic phase has been reported in patients treated with VEPESID in association with other antineoplastic agents.

Peripheral neuropathy has been reported in 0.7% of patients.

Nausea and vomiting are the major gastrointestinal toxicities. The severity of such nausea and vomiting is generally mild to moderate with treatment discontinuation required in 1% of patients. Nausea and vomiting can usually be controlled with standard antiemetic therapy. Gastrointestinal toxicities are slightly more frequent after oral administration than after i.v. infusion. Mild to severe mucositis/eosophagitis may occur.

Transient hypotension following rapid i.v. administration has been reported in 1 to 2% of patients. It has not been associated with cardiac toxicity or ECG changes. No delayed hypotension has been noted. To prevent this occurrence, it is recommended that VEPESID injection be administered by slow i.v. infusion over a 30- to 60-minute period. Hypotension usually responds to cessation of the infusion and/or other supportive therapy as appropriate. When restarting the infusion, a slower administration rate should be used.

Anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and/or hypotension have been reported to occur in 0.7 to 2% of patients during or immediately after i.v. VEPESID administration. Higher rates of anaphylactic-like reactions have been reported in children who received VEPESID infusions at concentrations higher than those recommended. The role that concentration of infusion (or rate of infusion) plays in the development of anaphylactic-like reactions is uncertain. Reactions have occurred very rarely in patients treated with oral capsules. Anaphylactic-like reactions have usually responded promptly to the cessation of the infusion of VEPESID, and subsequent administration of pressor agents, corticosteroids, antihistamines or volume expanders as appropriate. Acute fatal reactions associated with bronchospasm have been reported. Hypertension and/or flushing and/or seizures have also been reported. Blood pressure usually normalizes within a few hours after cessation of the infusion. Anaphylactic-like reactions can occur with the initial dose of VEPESID. Apnea with spontaneous resumption of breathing following discontinuation has been described in patients receiving etoposide infusion.