Paxoll Side Effects

Toxicity is more pronounced in the studies utilizing PAXOLL at a dose of 135 mg/m² every 3 weeks than in the study utilizing PAXOLL at a dose of 100 mg/m² every 2 weeks. Notably, severe neutropenia, febrile neutropenia, and opportunistic infections are more common with the former dose and schedule. Patients with AIDS-related Kaposi's sarcoma have more frequent and severe hematologic toxicity, infections, and febrile neutropenia. These patients require a lower dose intensity and supportive care.
Hematologic: Bone marrow suppression is the major dose-limiting toxicity of PAXOLL. Neutropenia, the most important hematologic toxicity, is dose and schedule dependent and is generally rapidly reversible. Among patients treated in the Phase III study in patients of ovarian cancer with a 3-hour infusion, neutrophil counts declined below 500 cells/mm³ in 13% of the patients treated with a dose of 135 mg/m² compared to 27% at a dose of 175 mg/m² (p=0.05). In the same study, severe neutropenia (<500 cells/mm³) is more frequent with the 24-hour than with the 3-hour infusion; infusion duration had a greater impact on myelosuppression than dose.
Fever is frequent episodes of sepsis, pneumonia, peritonitis and UTI and upper respiratory tract infections were the most frequently reported complications. The use of supportive therapy, including G-CSF, is recommended for patients who have experienced severe neutropenia. Thrombocytopenia is uncommon, and almost never severe (<50,000 cells/mm³). Anemia (Hb < 11 g/dL) is observed in 78% of all patients and is severe (Hb <8 g/dL) in 16% of the cases. No consistent relationship between dose of schedule and the frequency of anemia is observed.
Hypersensitivity Reactions (HSRs): The frequency and severity of HSRs are not affected by the dose or schedule of PAXOLL administration. Severe symptoms occurred generally within the first hour of PAXOLL infusion. The most frequent symptoms observed during these severe reactions were dyspnea, flushing chest pain and tachycardia. The minor hypersensitivity reactions consisted mostly of flushing rash, hypotension, dyspnea, tachycardia and hypertension. The frequency of hypersensitivity reactions remained relatively stable during the entire treatment period. Rare reports of chills and reports of back pain in association with hypersensitivity reactions have been received as proof of the continuing surveillance of PAXOLL safety.
Cardiovascular: Hypotension and bradycardia during the first 3 hours of infusion.
Significant cardiovascular events include syncope, rhythm abnormalities, hypertension and venous thrombosis. The arrhythmias included asymptomatic ventricular tachycardia, bigeminy and complete AV block requiring pacemaker placement.
Electrocardiogram (ECG) abnormalities are common among patients at baseline. The most frequently reported ECG modifications are non-specific repolarization abnormalities, sinus bradycardia, sinus tachycardia and premature beats. Among patients with normal ECGs at initiation of therapy, prior therapy with anthracyclines did not influence the frequency of ECG abnormalities. Cases of myocardial infarction have been reported rarely. Congestive heart failure has been reported typically in patients who have received other chemotherapy, notably anthracyclines. Rare reports of atrial fibrillation and supra-ventricular tachycardia have been received as proof of the continuing surveillance of PAXOLL safety.
Respiratory: Rare reports of interstitial pneumonia, lung fibrosis and pulmonary embolism have been reported as proof of the continuing surveillance of PAXOLL safety.
Rarely radiation pneumonitis has also been reported in patients receiving concurrent radiotherapy.
Neurologic: The frequency and severity of neurologic manifestations are dose­ dependent, but are not influenced by infusion duration. Peripheral neuropathy is observed without pre-existing neuropathy. The frequency of peripheral neuropathy increased with cumulative dose. Pre-existing neuropathies resulting from prior therapies are not a contraindication for PAXOLL therapy. Other than peripheral neuropathy, serious neurologic events following PAXOLL administration have been rare (<1%) and have included grand mal seizures, syncope, ataxia and neuroencephalopathy. Rare reports of autonomic neuropathy resulting in paralytic ileus and motor neuropathy with resultant minor distal weakness. Optic nerve and/or visual disturbance have been reported in patients who have received higher doses than those recommended.
Ototoxicity such as hearing loss and tinnitus has also been reported.
Arthralgia/Myalgia: There is no consistent relationship between dose or schedule of PAXOLL and the frequency or severity of arthralgia/myalgia. The symptoms are usually transient, occurring two or three days after PAXOLL administration and resolving within a few days.
Hepatic: No relationship is observed between liver function abnormalities and either dose or schedule of PAXOLL administration. Among patients with normal therapy liver function elevations in bilirubin, alkaline phosphatase and AST (SGOT) have been observed. Prolonged exposure to PAXOLL is not associated with any cumulative hepatic toxicity. Hepatic necrosis and hepatic encephalopathy leading to death have been reported rarely.
Renal: Among the patients treated for Kaposi's sarcoma with PAXOLL, renal toxicity grade III or IV has been observed. Renal insufficiency with elevations of serum creatinine have been reported.
Gastrointestinal (GI): Nausea/vomiting, diarrhea and mucositis have been reported. Rarely intestinal obstruction, perforation, pancreatitis, ischemicolitis, and dehydration have been observed. Neutropenic enterocolitis (typhilitis) has also been reported.
Injection Site Reaction: Injection site reactions, including reactions secondary to extravasation, are usually mild and consisted of erythema, tenderness. skin discoloration, or swelling at the injection site. These reactions have been observed more frequently with the 24-hour infusion than with the 3-hour infusion. More severe events such as phlebitis, cellulitis induration skin exfoliation, necrosis and fibrosis have been reported.
Other Clinical Events: Alopecia is observed in almost all the patients. Transient skin changes, nail changes, edema is reported and none of these patients required treatment discontinuation. Maculopapular rash, pruritus, Stevens-Jonson syndrome, and toxic epidermal necrolysis have been reported rarely. Asthenia and malaise have also been reported.