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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.

Drugs That Inhibit Drug Efflux Transporters

Topotecan is a substrate for both ABCB1 [P-glycoprotein (P-gp)] and ABCG2 (BCRP). Elacridar (inhibitor of ABCB1 and ABCG2) administered with HYCAMTIN capsules increased topotecan exposure to approximately 2.5-fold of control. Cyclosporine A (inhibitor of ABCB1, ABCC1 [MRP-1], and CYP3A4) with HYCAMTIN capsules increased topotecan exposure to 2- to 3-fold of control. Patients should be carefully monitored for adverse reactions when HYCAMTIN capsules are administered with a drug known to inhibit these transporters. [See CLINICAL PHARMACOLOGY.]

Effects of Topotecan on Drug Metabolizing Enzymes

In vitro inhibition studies using marker substrates known to be metabolized by human cytochromes P450 (CYP1A2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E, CYP3A, or CYP4A) or dihydropyrimidine dehydrogenase indicate that the activities of these enzymes were not altered by topotecan. Enzyme inhibition by topotecan has not been evaluated in vivo.

Effects of Other Drugs on Topotecan Pharmacokinetics

The pharmacokinetics of topotecan were generally unchanged when coadministered with ranitidine.

Last reviewed on RxList: 10/28/2011
This monograph has been modified to include the generic and brand name in many instances.