Drug Information for RISPERDAL CONSTA (risperidone) LONG-ACTING INJECTIONGEMZAR (gemcitabine hydrochloride) Injection, Powder, Lyophilized, For Solution For Intravenous Use (Eli Lilly and Company ): 5 WARNINGS AND PRECAUTIONS

  • Patients receiving therapy with Gemzar should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.

  • 5.1 Infusion Time

  • Caution — Prolongation of the infusion time beyond 60 minutes and more frequent than weekly dosing have been shown to increase toxicity [see Clinical Studies (14.5)].

  • 5.2 Hematology

  • Gemzar can suppress bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia [see Adverse Reactions (6.1)], and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy. [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)]

  • 5.3 Pulmonary

  • Pulmonary toxicity has been reported with the use of Gemzar. In cases of severe lung toxicity, Gemzar therapy should be discontinued immediately and appropriate supportive care measures instituted [see Adverse Reactions (6.1 and 6.2)].

  • 5.4 Renal

  • Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been reported. The majority of the cases of renal failure leading to death were due to HUS [see Adverse Reactions (6.1 and 6.2)]. Gemzar should be used with caution in patients with preexisting renal impairment as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. [see Use In Specific Populations (8.6)]

  • 5.5 Hepatic

  • Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar alone or in combination with other potentially hepatotoxic drugs [see Adverse Reactions (6.1 and 6.2)]. Gemzar should be used with caution in patients with preexisting hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. Administration of Gemzar in patients with concurrent liver metastases or a preexisting medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency. [see Use In Specific Populations (8.7)]

  • 5.6 Pregnancy

  • Gemzar can cause fetal harm when administered to a pregnant woman. In pre-clinical studies in mice and rabbits, gemcitabine was teratogenic, embryotoxic, and fetotoxic. There are no adequate and well-controlled studies of Gemzar in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. [see Use In Specific Populations (8.1)]

  • 5.7 Laboratory Tests

  • Patients receiving Gemzar should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. Suspension or modification of therapy should be considered when marrow suppression is detected. [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)]

    Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter [see Dosage and Administration (2.4)].

  • 5.8 Radiation Therapy

  • A pattern of tissue injury typically associated with radiation toxicity has been reported in association with concurrent and non-concurrent use of Gemzar.

  • Non-concurrent (given >7 days apart) — Analysis of the data does not indicate enhanced toxicity when Gemzar is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that Gemzar can be started after the acute effects of radiation have resolved or at least one week after radiation.

  • Concurrent (given together or =7 days apart) — Preclinical and clinical studies have shown that Gemzar has radiosensitizing activity. Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of Gemzar, frequency of Gemzar administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. In a single trial, where Gemzar at a dose of 1000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life-threatening mucositis, especially esophagitis and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4795 cm3]. Subsequent studies have been reported and suggest that Gemzar administered at lower doses with concurrent radiotherapy has predictable and less severe toxicity. However, the optimum regimen for safe administration of Gemzar with therapeutic doses of radiation has not yet been determined in all tumor types.

  • Drug Information Provided by National Library of Medicine (NLM).