UNDESIRABLE EFFECTS

Hematologic Effects: Bone marrow suppression is the major and dose-limiting adverse effect. Dose-related myelosuppression is manifested mainly by leukopenia, thrombocytopenia and anemia. The frequency and severity of hematologic toxicity increase with dose, especially at paclitaxel doses exceeding 190 mg/m² . Eosinophilia was reported in patients with AIDS-related Kaposi’s sarcoma. Few reports of severe hemorrhage were also attributed to paclitaxel.

Dose- and schedule-dependent paclitaxel-induced neutropenia is generally rapidly reversible. The onset of neutropenia usually occurs 8 to 10 days and neutrophil nadirs generally occur at a median of 10 to 12 days after paclitaxel administration. Neutrophil counts commonly recover 15 to 21 days after administration.

Febrile neutropenia associated with infectious episode, including UTI and upper respiratory tract infection (URTI) have been commonly reported.

Infectious Complications: Fever was associated with 12% of all paclitaxel courses (as single agent) in patients with solid tumors. Most frequently reported were urinary and respiratory tract infections. Infectious complications, including sepsis, pneumonia and peritonitis were also reported. Infectious episodes were fatal in 1% of all patients.

Hypersensitivity Reactions: Flushing, rash, skin reactions, dyspnea, hypotension, tachycardia, hypertension, chest pains, angioedema, and generalized urticaria which are mostly mild in severity may occur in patients receiving paclitaxel. These reactions occur frequently in clinical trials despite premedication. Chills and back pain associated with hypersensitivity to paclitaxel have been reported. Other cutaneous reactions such as acral erythema, generalized pustular dermatosis, and bullous fixed drug eruption have also been reported. 

GI Effects: Nausea and vomiting, diarrhea, anorexia, taste perversion, mucositis characterized by diffuse ulceration of the lips, oral cavity and pharynx have been reported. Dysphagia and pain reflecting esophageal involvement may also occur. Rare reports of intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, and dehydration have been reported. Neutropenic enterocolitis (typhlitis) has been observed despite co-administration of G-CSF.

Adverse GI effects of paclitaxel are generally mild to moderate in severity at current recommended doses.

Hepatic Effects:  Abnormalities in liver function test results have occurred; increased serum alkaline phosphatase, AST, ALT and bilirubin concentrations have been reported in patients with normal baseline hepatic function. Cumulative hepatic toxicity has been associated with prolonged exposure to paclitaxel. Hepatic necrosis and hepatic encephalopathy resulting in death have occurred rarely. Fatal hepatic coma has also occurred.

Renal Effects: Renal toxicity including acute renal failure and reversible increases in serum creatinine levels have been reported.

CV Effects: HTN and bradycardia are the most common CV adverse effects of paclitaxel. These are generally asymptomatic and do not require treatment.

ECG abnormalities including nonspecific repolarization, sinus bradycardia, sinus tachycardia, and premature beats were seen in paclitaxel-treated patients.

Chest pain and hypertension are often associated with hypersensitivity reactions.

Severe CV effects include arrhythmia (e.g., asymptomatic ventricular tachycardia, bigeminy, atrial fibrillation, supraventricular tachycardia, junctional tachycardia), syncope, HTN, venous thrombosis, and severe conduction abnormalities. Cerebrovascular infarction, vascular toxicity, including MI have been reported rarely; AV block has also been reported.

CHF and cardiomyopathy associated with acute renal failure have been reported; edema has also been reported.

Respiratory Effects: Rare reports of interstitial pneumonia, lung fibrosis and pulmonary embolism. Paclitaxel together with radiation therapy may cause radiation pneumonitis and interstitial pneumonia. Transient pulmonary infiltrates has also been reported.

Dermatologic Effects: Patients receiving paclitaxel may experience reversible alopecia, loss of all body hair including axillary, pubic and extremity hair, eyelashes, and eyebrows. Transient skin changes, nail changes (changes in pigmentation, discoloration of nail bed), radiation recall dermatitis resulting in extensive desquamation and necrosis, and maculopapular rash may occur. Pruritus was reported in patients receiving high-dose paclitaxel.

Ocular Effects: High dose paclitaxel may result in loss of visual acuity. Abnormalities observed in visual evoked potentials in some patients suggest persistent damage of the optic nerve. Other visual problems encountered include scintillating scotomata and photopsia which appear to be reversible.

Nervous System Effects: Peripheral neuropathy manifested as mild paresthesia with numbness and tingling in a stocking-glove distribution have been reported. Burning pain (often associated with hyperesthesia), particularly in the feet, and perioral numbness have also been reported.

Seizures (including tonoclonic seizures), syncope, ataxia, and neuroencephalopathy have occurred rarely during or immediately after administration of paclitaxel. Autonomic neuropathy resulting in paralytic ileus has also been reported rarely.

Musculoskeletal Effects: Arthralgia and/or myalgia consisting of pain in the large joints of the arms and legs have been reported.

Injection Site Reaction: Erythema, tenderness, skin discoloration, or swelling at the injection site may occur. Recurrence of skin reactions at a previous site of extravasation (i.e., “recall” reactions) after paclitaxel administration at a different injection site has been reported rarely. More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have also been reported rarely.

Accidental Exposure:

• Inhalation: Dyspnea, chest pain, burning eyes, sore throat and nausea. 
• Topical:  Tingling, burning and redness. 

Others: Asthenia and malaise.