SIDE EFFECTS

Clinical Trials Experience

The safety of HYCAMTIN capsules has been evaluated in 682 patients with thoracic cancer (3 recurrent small cell lung cancer [SCLC] studies and 1 recurrent non-small cell lung cancer [NSCLC] study) who received at least one dose of HYCAMTIN capsules. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Table 1 describes the hematologic and non-hematologic adverse reactions in recurrent SCLC patients treated with HYCAMTIN capsules plus best supportive care (BSC) and in the overall thoracic cancer patient population.

Table 1: Incidence ( ≥ 5%) of Adverse Reactions in Small Cell Lung Cancer Patients Treated With HYCAMTIN Capsules Plus BSC and in 4 Thoracic Cancer Studies

Diarrhea Adverse Reactions

Of the 70 patients who received HYCAMTIN capsules plus BSC, the incidence of drug-related diarrhea was 14%, with 4% Grade 3 and 1% Grade 4.

In the 682 patients who received HYCAMTIN capsules in the 4 thoracic cancer studies, the incidence of drug-related diarrhea was 22%, with 4% Grade 3 and 0.4% Grade 4. The overall incidence of drug-related diarrhea was more frequent in patients ≥ 65 years of age (28%, n = 225) with 10% Grade 1, 9% Grade 2, 7% Grade 3, and 1% Grade 4 compared to those < 65 years of age (19%, n = 457) with 7% Grade 1, 9% Grade 2, 3% Grade 3, and 0% Grade 4. The incidence of Grade 3 or 4 diarrhea proximate (within 5 days) to Grade 3 or 4 neutropenia events in the HYCAMTIN capsules treatment group was 5%. The median time to onset of Grade 2 or worse diarrhea was 9 days in the HYCAMTIN capsules group.

Deaths Occurring Within 30 Days Following the Last Dose of Study Medication

In the 682 patients who received HYCAMTIN capsules in the 4 thoracic cancer studies, 39 deaths occurred within 30 days after the last dose of study medication for a reason other than progressive disease; 13 of these deaths were attributed to hematologic toxicity, 5 were attributed to non-hematologic toxicity, and 21 were attributed to other causes. One patient death (68 years of age) was attributed to treatment-related diarrhea and one death (68 years of age) attributed diarrhea as a contributory event; both patients received HYCAMTIN capsules.

In addition to the adverse reactions listed previously, the following adverse reactions have been reported with HYCAMTIN for Injection:

• Incidence > 10%: Febrile neutropenia, abdominal pain, stomatitis, constipation.
• Incidence 1 to 10%: Sepsis, hypersensitivity (including rash), hyperbilirubinemia, malaise.

Postmarketing Experience

There is no postmarketing experience with HYCAMTIN capsules. The following adverse reactions have been identified during post-approval use of HYCAMTIN for Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: Severe bleeding (in association with thrombocytopenia).

Immune system disorders: Allergic manifestations, anaphylactoid reactions.

Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease.

Gastrointestinal disorders: Abdominal pain potentially associated with neutropenic colitis [see WARNINGS AND PRECAUTIONS].

Skin and subcutaneous tissue disorders: Angioedema, severe dermatitis, severe pruritus.

Read the entire FDA prescribing information for Hycamtin (Topotecan Hydrochloride) »