جم سیتابین
Gemcitabine Hcl (Gemzar)
جم سیتابین

نام ژنریک

Gemcitabine Hydrochloride

شکل دارویی

اشكال دارويي:


Injection, Powder, Lyophilized: 200mg,1g

موارد مصرف

موارد و مقدار مصرف


الف) آدنوكارسينوم موضعي پيشرفته (غير قابل برداشت مرحله 2 يا 3) يا متاستاتيك (مرحله 4) پانكراس و در بيماراني كه قبلاً با فلورواوراسيل درمان شده‌اند.


بزرگسالان: mg/m2 1000 وريدي در عرض 30 دقيقه هفته‌اي يك بار تا 7 روز يا تا زماني كه بدليل سميت نياز به كاهش دوز يا قطع موقت دارو باشد. طول درمان 7 هفته پشت سر هم و سپس يك هفته استراحت مي‌باشد. دوره‌هاي بعدي درمان انفوزيون دارو به صورت هفتگي براي 3 هفته از 4 هفته متوالي مي‌باشد.


تنظيم دوز: در صورت ساپرس شدن مغز استخوان دوز را تنظيم كنيد. اگر تعداد مطلق گرانولوسيت (AGC) بين mm3 /500 تا mm3 /999 يا اگر تعداد پلاكت بين mm3/ 50000 تا mm3 /99000 مي‌باشد، 75% دوز تجويز شود. اگر AGC كمتر از mm3 /500 يا تعداد پلاكت كمتر از mm3 /50000 تجويز دارو متوقف شود. در سيكل‌هاي بعدي درمان دوز را براساس AGC و تعداد پلاكت و ميزان ساير عوارض غير هماتولوژيك تنظيم كنيد.


ب) كارسينوم‌ريه با سلولهاي بزرگ (non-small-cell) غير قابل جراحي موضعي، پيشرفته (مرحله A3 يا B3) يا متاستاتيك (مرحله 4) به عنوان درمان اوليه همراه با سيس‌پلاتين.


دوره درمان 4 هفته‌اي:


بزرگسالان: mg/m2 1000 وريدي در عرض 30 دقيقه در روزهاي 1، 8 و 15 از يك سيكل 28 روزه تجويز شود. سيس‌پلاتين در روز اول بعد از اتمام دوز جم سيتابين تجويز مي‌شود.


دوره درمان 3 هفته‌اي:


بزرگسالان: mg/m2 1250 وريدي در عرض 30 دقيقه در روز اول و هشتم از هر سيكل 21 روزه تجويز شود. سيس‌پلاتين در روز اول بعد از اتمام دوز جم سيتابين تجويز مي‌شود.


تنظيم دوز: در مصرف همزمان با سيس‌پلاتين و وقوع عوارض غيرهماتولوژيك شديد، دوز را به 50% كاهش دهيد.


پ) در سرطان متاستاتيك سينه به عنوان خط اول همراه با پاكلي تاكسول بعد از اينكه يك دوره درمان با يك آنتراسيكلين موفق نبوده است.


بزرگسالان: mg/m2 1250 وريدي در عرض 30 دقيقه در روز اول و هشتم از هر سيكل 21 روزه، به همراه mg/m2 1750 پاكلي‌تاكسول وريدي در عرض 30 دقيقه كه در روز اول قبل از جم‌سيتابين تجويز مي‌شود. دوز را براساس تعداد مطلق گرانولوسيت و پلاكت كه روز هشتم درمان گرفته مي‌شود، تنظيم كنيد.


ت) سرطان پيشرفته تخمدان كه 6 ماه بعد از اتمام يك دوره درمان حاوي پلاتينوم عود كرده باشد(به همراه كربوپلاتين).


بزرگسالان: mg/m2 1000 وريدي در عرض 30 دقيقه در روز اول و هشتم از هر سيكل 21 روزه تجويز شود. كربوپلاتين به ميزان AUC 4 وريدي در روز اول بعد از جم‌سيتابين تجويز مي‌شود. قبل از تجويز هر دوز CBC و تعداد پلاكت را چك كنيد.


تعداد مطلق گرانولوسيت (AGC) بايد mm3 /1500 يا بيشتر، و تعداد پلاكت mm3 /100000 يا بيشتر قبل از شروع هر دوره درماني بايد باشد.


تنظيم دوز: بر مبناي تعداد مطلق گرانولوسيت و پلاكت در روز 8 هر سيكل صورت مي‌گيرد. اگر AGC بين 1000 تا mm3 /1499 است. دوز را 50%
كاهش دهيد. اگر ميزان AGC كمتر از mm3 /1000 يا تعداد پلاكت كمتر از mm3 /75000 است، تجويز دارو را متوقف كنيد. تنظيم دوز براي سيكل‌هاي بعدي درمان بر مبناي عوارض مشاهده شده صورت مي‌گيرد.


ث) سرطان پيشرفته يا متاستاتيك مثانه.


بزرگسالان: mg/m2 1250-1200 وريدي در عرض 30 دقيقه هفتگي به مدت 3 هفته از 4 هفته يك سيكل درماني تجويز شود.

موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت به دارو يا ديگر اجزاء فرمولاسيون؛ حاملگي.


موارد احتياط: دارو باعث سركوب مغز استخوان مي‌شود (لكوپني؛ ترومبوسيتوپني و آنمي). اين عارضه، عارضه محدود كننده دوز دارو است.


ممكن است بدون وجود علايم باليني عفونت باعث ايجاد تب شود.


مصرف دارو باعث سندرم هموليتيك اورميك مي‌شود. در ضمن درمان بيمار را از نظر علائم هموليز ميكروآنژيوپاتيك (افزايش بيلي‌روبين يا LDH، رتيكولوسيتوز، ترومبوسيتوپني شديد و نارسايي كليوي) بررسي كنيد.


دارو مي‌تواند باعث سميت كبدي شديد شود. در بيماران با سابقه نارسايي كبدي (سابقه سيروز، هپاتيت يا الكليسم) با احتياط به كار رود.


همچنين با مصرف دارو سميت ريوي گزارش شده است، در صورت بروز علائم شديد، مصرف دارو قطع شود.


در افراد با نارسايي كليوي، افراد مسن با احتياط استفاده شود. اثربخشي دارو در كودكان اثبات نشده است.


در كساني كه همزمان راديوتراپي مي‌شوند يا سابقه آن را دارند با احتياط به كار رود. در صورتي كه كمتر از 7 روز بين اين دارو و راديوتراپي فاصله باشد، باعث ايجاد واكنشهاي حساسيتي مي‌شود.


تجويز دارو به صورت انفوزيون طولاني مدت (بيشتر از 60 دقيقه) يا با فواصل كمتر از يك هفته يك بار، سميت آن را افزايش مي‌دهد.

عوارض جانبی دارو

عوارض جانبي


اعصاب مرکزي: تب، درد، پارستزي، خواب آلودگي.


قلبي- عروقي: ادم، خونريزي، ادم محيطي .


دستگاه گوارش: يبوست، اسهال، تهوع، استوماتيت، استفراغ.


ادراري- تناسلي: هماچوري، پروتئين اوري.


خون: آنمي، لكوپني، نوتروپني، ترومبوسيتوپني.


تنفسي: برونكواسپاسم، تنگي نفس.


پوست: آلوپسي، راش.


ساير عوارض: علائم شبه آنفلونزا، عفونت.


مسموميت و درمان


آنتي‌دوت اختصاصي براي دارو وجود ندارد. در صورت احتمال مصرف بيش از حد بيمار را با CBC مانيتور كرده و درمان حمايتي انجام دهيد.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


موردي گزارش نشده است.

مکانیزم اثر

تداخل دارويي


موردي گزارش نشده است.

فارماكوكینتیك

فارماكوكينتيك


جذب: به صورت وريدي تجويز مي‌شود.


پخش: با افزايش مدت زمان انفوزيون، حجم توزيع دارو افزايش مي‌يابد. در صورتي كه مدت انفوزيون كمتر از 70 دقيقه باشد، حجم توزيع دارو L/m2 50 است كه نشانگر توزيع نسبتاً كم دارو است. در انفوزيونهاي طولاني مدت‌تر حجم توزيع L/m2 370 افزايش مي‌يابد. كه بيانگر به تعادل رسيدن آهسته دارو با بافت مي‌باشد.


اتصال دارو به پروتئينهاي پلاسما ناچيز است. هرچه زمان انفوزيون طولاني‌تر باشد، نيمه‌ عمر دارو هم طولاني‌تر است.


متابوليسم: دارو به دو متابوليت فعال و يك متابوليت غيرفعال اوراسيل تبديل مي‌شود.


دفع: با افزايش سن كليرنس دارو كاهش مي‌يابد. در ضمن كليرنس در خانمها كمتر از آقايان است. در نتيجه نيمه‌ عمر دارو در افراد مسن و خانمها بيشتر است.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: آنالوگ نوكلئوزيد پيريميدين.


طبقه‌بندي درماني: ضد نئوپلاسم.


طبقه‌بندي مصرف در بارداري: رده D


نامهاي تجاري Gemcitabine Hospira, Gemtaz, Gemzar


ملاحظات اختصاصي
1- آماده كردن دارو جهت تزريق خطرات موتاژنيك، تراتوژنيك و كارسينوژنيك را براي پرسنل به همراه دارد.


2- تجويز دارو براي مدت بيشتر از 60 دقيقه و در فواصل كمتر از يك هفته، سميت آن را افزايش مي‌دهد.


3- سن، جنس و نارسايي كليوي احتمال سميت ناشي از دارو را افزايش مي‌دهند.


4- در نارسايي كبدي و كليوي دارو با احتياط استفاده شود.


5- قبل از هر سكيل درماني CBC و پلاكت بيمار را مانيتور كنيد.


نكات قابل توصيه به بيمار


بهتر است بيمار هر روز دماي بدن خود را اندازه‌گيري كرده و مراقب علائم عفونت (تب، گلودرد، خستگي) و خونريزي (كبودشدگي، خونريزي از بيني و لثه و مدفوع خوني) باشد.


مصرف در سالمندان: كليرنس دارو با افزايش سن تغيير مي‌كند. هرچند تنظيم دوز ضرورتي ندارد.


مصرف در كودكان: اين دارو در كودكان مطالعه نشده است.


مصرف در شيردهي: ترشح دارو در شير مشخص نيست. در دوران شيردهي توصيه نمي‌شود.


اثر بر آزمايشهاي تشخيصي


دارو باعث افزايش كراتينين، BUN، ALT و AST مي‌شود. ميزان WBC، نوتروفيل، پلاكت، هموگلوبين و هماتوكريت را كاهش مي‌دهد.

Gemcitabine Hcl (Gemzar)

GEMZAR
(gemcitabine for injection) Powder, Lyophilized, For Solution For Intravenous Use

DRUG DESCRIPTION

Gemzar (gemcitabine for injection, USP) is a nucleoside metabolic inhibitor that exhibits antitumor activity. Gemcitabine HC1 is 2'-deoxy-2',2'-difluorocytidine monohydrochloride (β-isomer).

The structural formula is as follows:

GEMZAR
  (gemcitabine for injection) Powder  Structural Formula Illustration

The empirical formula for gemcitabine HC1 is C9H11F2N3O4·HCI It has a molecular weight of 299.66.

Gemcitabine HC1 is a white to off-white solid. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.

The clinical formulation is supplied in a sterile form for intravenous use only. Vials of Gemzar (gemcitabine hcl) contain either 200 mg or 1 g of gemcitabine HC1 (expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.

What are the possible side effects of gemcitabine (Gemzar)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • pale skin, easy bruising or bleeding, unusual weakness;
  • urinating less than usual or not at all;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general...

Read All Potential Side Effects and See Pictures of Gemzar »

What are the precautions when taking gemcitabine hcl (Gemzar)?

Before using gemcitabine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bone marrow problems (e.g., leukopenia, thrombocytopenia, anemia), heart problems (e.g., irregular heartbeat, heart failure), kidney problems, liver problems, radiation therapy.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine.

Wash your hands well to prevent the spread of infections.

To lower the chance...

Read All Potential Precautions of Gemzar »

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Ovarian Cancer

Gemzar (gemcitabine hcl) in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.

Breast Cancer

Gemzar (gemcitabine hcl) in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.

Non-Small Cell Lung Cancer

Gemzar (gemcitabine hcl) is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.

Pancreatic Cancer

Gemzar (gemcitabine hcl) is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemzar (gemcitabine hcl) is indicated for patients previously treated with 5-FU.

DOSAGE AND ADMINISTRATION

Gemzar (gemcitabine hcl) is for intravenous use only. Gemzar (gemcitabine hcl) may be administered on an outpatient basis.

Ovarian Cancer

Gemzar (gemcitabine hcl) should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Carboplatin AUC 4 should be administered intravenously on Day 1 after Gemzar (gemcitabine hcl) administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥ 1500 x 106/L and a platelet count ≥ 100,000 x 106/L prior to each cycle.

Dose Modifications

Gemzar (gemcitabine hcl) dosage adjustment for hematological toxicity within a cycle of treatment is based on the granulocyte and platelet counts taken on Day 8 of therapy. If marrow suppression is detected, Gemzar (gemcitabine hcl) dosage should be modified according to guidelines in Table 1.

Table 1: Day 8 Dosage Reduction Guidelines for Gemzar (gemcitabine hcl) in Combination with Carboplatin

Absolute granulocyte count
(x 106/L)
  Platelet count
(x 106/L)
% of full dose
≥ 1500 And ≥ 100,000 100
1000-1499 and/or 75,000-99,999 50
< 1000 and/or < 75,000 Hold

In general, for severe (Grade 3 or 4) non-hematological toxicity, except nausea/vomiting, therapy with Gemzar (gemcitabine hcl) should be held or decreased by 50% depending on the judgment of the treating physician. For carboplatin dosage adjustment, see manufacturer's prescribing information.

Dose adjustment for Gemzar (gemcitabine hcl) in combination with carboplatin for subsequent cycles is based upon observed toxicity. The dose of Gemzar (gemcitabine hcl) in subsequent cycles should be reduced to 800 mg/m2 on Days 1 and 8 in case of any of the following hematologic toxicities:

  • Absolute granulocyte count < 500 x 106/L for more than 5 days
  • Absolute granulocyte count < 100 x 106/L for more than 3 days Febrile neutropenia
  • Platelets < 25,000 x 106/L
  • Cycle delay of more than one week due to toxicity

If any of the above toxicities recur after the initial dose reduction, for the subsequent cycle, Gemzar (gemcitabine hcl) should be given on Day 1 only at 800 mg/m2.

Breast Cancer

Gemzar (gemcitabine hcl) should be administered intravenously at a dose of 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Paclitaxel should be administered at 175 mg/m2 on Day 1 as a 3-hour intravenous infusion before Gemzar (gemcitabine hcl) administration. Patients should be monitored prior to each dose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count ≥ 1500 x 106/L and a platelet count ≥ 100,000 x 106/L prior to each cycle.

Dose Modifications

Gemzar (gemcitabine hcl) dosage adjustment for hematological toxicity is based on the granulocyte and platelet counts taken on Day 8 of therapy. If marrow suppression is detected, Gemzar (gemcitabine hcl) dosage should be modified according to the guidelines in Table 2.

Table 2: Day 8 Dosage Reduction Guidelines for Gemzar (gemcitabine hcl) in Combination with Paclitaxel

Absolute granulocyte count
(x 106/L)
  Platelet count
(x 106/L)
% of full dose
≥ 1200 And > 75,000 100
1000-1199 Or 50,000-75,000 75
700-999 And ≥ 50,000 50
< 700 Or < 50,000 Hold

In general, for severe (Grade 3 or 4) non-hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar (gemcitabine hcl) should be held or decreased by 50% depending on the judgment of the treating physician. For paclitaxel dosage adjustment, see manufacturer's prescribing information.

Non-Small Cell Lung Cancer

Two schedules have been investigated and the optimum schedule has not been determined [see Clinical Studies]. With the 4-week schedule, Gemzar (gemcitabine hcl) should be administered intravenously at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Cisplatin should be administered intravenously at 100 mg/m2 on Day 1 after the infusion of Gemzar (gemcitabine hcl) . With the 3-week schedule, Gemzar (gemcitabine hcl) should be administered intravenously at 1250 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Cisplatin at a dose of 100 mg/m2 should be administered intravenously after the infusion of Gemzar (gemcitabine hcl) on Day 1. See prescribing information for cisplatin administration and hydration guidelines.

Dose Modifications

Dosage adjustments for hematologic toxicity may be required for Gemzar (gemcitabine hcl) and for cisplatin. Gemzar (gemcitabine hcl) dosage adjustment for hematological toxicity is based on the granulocyte and platelet counts taken on the day of therapy. Patients receiving Gemzar (gemcitabine hcl) should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet counts. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 3. For cisplatin dosage adjustment, see manufacturer's prescribing information.

In general, for severe (Grade 3 or 4) non-hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar (gemcitabine hcl) plus cisplatin should be held or decreased by 50% depending on the judgment of the treating physician. During combination therapy with cisplatin, serum creatinine, serum potassium, serum calcium, and serum magnesium should be carefully monitored (Grade 3/4 serum creatinine toxicity for Gemzar (gemcitabine hcl) plus cisplatin was 5% versus 2% for cisplatin alone).

Pancreatic Cancer

Gemzar (gemcitabine hcl) should be administered by intravenous infusion at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks.

Dose Modifications

Dosage adjustment is based upon the degree of hematologic toxicity experienced by the patient [see WARNINGS AND PRECAUTIONS]. Clearance in women and the elderly is reduced and women were somewhat less able to progress to subsequent cycles [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Patients receiving Gemzar (gemcitabine hcl) should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 3.

Table 3: Dosage Reduction Guidelines

Absolute granulocyte count
(x 106/L)
  Platelet count
(x 106/L)
% of full dose
≥ 1000 And ≥ 100,000 100
500-999 Or 50,000-99,999 75
< 500 Or < 50,000 Hold

Laboratory evaluation of renal and hepatic function, including transaminases and serum creatinine, should be performed prior to initiation of therapy and periodically thereafter. Gemzar (gemcitabine hcl) should be administered with caution in patients with evidence of significant renal or hepatic impairment as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations.

Patients treated with Gemzar (gemcitabine hcl) who complete an entire cycle of therapy may have the dose for subsequent cycles increased by 25%, provided that the absolute granulocyte count (AGC) and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and if non-hematologic toxicity has not been greater than WHO Grade 1. If patients tolerate the subsequent course of Gemzar (gemcitabine hcl) at the increased dose, the dose for the next cycle can be further increased by 20%, provided again that the AGC and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and that non-hematologic toxicity has not been greater than WHO Grade 1.

Preparation and Administration Precautions

Caution should be exercised in handling and preparing Gemzar (gemcitabine hcl) solutions. The use of gloves is recommended. If Gemzar (gemcitabine hcl) solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water. Although acute dermal irritation has not been observed in animal studies, 2 of 3 rabbits exhibited drug-related systemic toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal absorption.

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published [see References].

Preparation for Intravenous Infusion Administration

The recommended diluent for reconstitution of Gemzar (gemcitabine hcl) is 0.9% Sodium Chloride Injection without preservatives. Due to solubility considerations, the maximum concentration for Gemzar (gemcitabine hcl) upon reconstitution is 40 mg/mL. Reconstitution at concentrations greater than 40 mg/mL may result in incomplete dissolution, and should be avoided.

To reconstitute, add 5 mL of 0.9% Sodium Chloride Injection to the 200-mg vial or 25 mL of 0.9% Sodium Chloride Injection to the 1-g vial. Shake to dissolve. These dilutions each yield a gemcitabine concentration of 38 mg/mL which includes accounting for the displacement volume of the lyophilized powder (0.26 mL for the 200-mg vial or 1.3 mL for the 1-g vial). The total volume upon reconstitution will be 5.26 mL or 26.3 mL, respectively. Complete withdrawal of the vial contents will provide 200 mg or 1 g of gemcitabine, respectively. Prior to administration the appropriate amount of drug must be diluted with 0.9% Sodium Chloride Injection. Final concentrations may be as low as 0.1 mg/mL.

Reconstituted Gemzar (gemcitabine hcl) is a clear, colorless to light straw-colored solution. After reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting solution lies in the range of 2.7 to 3.3. The solution should be inspected visually for paniculate matter and discoloration prior to administration, whenever solution or container permit. If particulate matter or discoloration is found, do not administer.

When prepared as directed, Gemzar (gemcitabine hcl) solutions are stable for 24 hours at controlled room temperature 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Discard unused portion. Solutions of reconstituted Gemzar (gemcitabine hcl) should not be refrigerated, as crystallization may occur.

The compatibility of Gemzar (gemcitabine hcl) with other drugs has not been studied. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.

HOW SUPPLIED

Dosage Forms and Strengths

Gemzar (gemcitabine for injection, USP) is a white to off-white lyophilized powder available in sterile single-use vials containing 200 mg or 1 g gemcitabine.

Gemzar (gemcitabine for injection, USP), is available in sterile single-use vials individually packaged in a carton containing:

200 mg white to off-white, lyophilized powder in a 10-mL size sterile single-use vial - NDC 0002-7501-01 (No. 7501)

1 g white to off-white, lyophilized powder in a 50-mL size sterile single-use vial - NDC 0002-7502-01 (No. 7502)

Storage and Handling

Unopened vials of Gemzar (gemcitabine hcl) are stable until the expiration date indicated on the package when stored at controlled room temperature 20° to 25°C (68° to 77°F) and that allows for excursions between 15° and 30°C (59° and 86°F) [See USP Controlled Room Temperature] [see DOSAGE AND ADMINISTRATION].

Eli Lilly and Company, Indianapolis, IN 46285, USA. Eli Lilly and Company.

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience

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.

Most adverse reactions are reversible and do not need to result in discontinuation, although doses may need to be withheld or reduced.

Gemzar (gemcitabine hcl) has been used in a wide variety of malignancies, both as a single-agent and in combination with other cytotoxic drugs.

Single-Agent Use

Myelosuppression is the principal dose-limiting toxicity with Gemzar (gemcitabine hcl) therapy. Dosage adjustments for hematologic toxicity are frequently needed [see DOSAGE AND ADMINISTRATION].

The data in Table 4 are based on 979 patients receiving Gemzar (gemcitabine hcl) as a single-agent administered weekly as a 30-minute infusion for treatment of a wide variety of malignancies. The Gemzar (gemcitabine hcl) starting doses ranged from 800 to 1250 mg/m2. Data are also shown for the subset of patients with pancreatic cancer treated in 5 clinical studies. The frequency of all grades and severe (WHO Grade 3 or 4) adverse reactions were generally similar in the single-agent safety database of 979 patients and the subset of patients with pancreatic cancer. Adverse reactions reported in the single-agent safety database resulted in discontinuation of Gemzar (gemcitabine hcl) therapy in about 10% of patients. In the comparative trial in pancreatic cancer, the discontinuation rate for adverse reactions was 14.3% for the Gemzar (gemcitabine hcl) arm and 4.8% for the 5-FU arm. All WHO-graded laboratory adverse reactions are listed in Table 4, regardless of causality. Non-laboratory adverse reactions listed in Table 4 or discussed below were those reported, regardless of causality, for at least 10% of all patients, except the categories of Extravasation, Allergic, and Cardiovascular and certain specific adverse reactions under the Renal, Pulmonary, and Infection categories.

Table 4: Selected WHO-Graded Adverse Reactions in Patients Receiving Single-Agent Gemzar (gemcitabine hcl) WHO Grades (% incidence)a

  All Patientsb Pancreatic Cancer Patientsc Discontinuations (%)d
All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 All Patients
Laboratorye
Hematologic              
  Anemia 68 7 1 73 8 2 < 1
  Leukopenia 62 9 < I 64 8 1 < 1
  Neutropenia 63 19 6 61 17 7 -
  Thrombocytopenia 24 4 1 36 7 < 1 < 1
Hepatic             < 1
  ALT 68 8 2 72 10 1  
  AST 67 6 2 78 12 5  
  Alkaline Phosohatase 55 7 2 77 16 4  
  Bilirubin 13 2 < 1 26 6 2  
Renal             < 1
  Proteinuria 45 < 1 0 32 < 1 0  
  Hematuria 35 < 1 0 23 0 0  
  BUN 16 0 0 15 0 0  
  Creatinine 8 < 1 0 6 0 0  
Non-Iaboratoryf
  Nausea and Vomiting 69 13 1 71 10 2 < 1
  Fever 41 2 0 38 2 0 < 1
  Rash 30 < 1 0 28 < 1 0 < 1
  Dyspnea 23 3 < 1 10 0 < 1 < 1
  Diarrhea 19 1 0 30 3 0 0
  Hemorrhage 17 < 1 < 1 4 2 < 1 < 1
  Infection 16 1 < 1 10 2 < 1 < 1
  Alopecia 15 < 1 0 16 0 0 0
  Stomatitis 11 < 1 0 10 < 1 0 < 1
  Somnolence 11 < 1 < 1 11 2 < 1 < 1
  Paresthesias 10 < 1 0 10 < 1 0 0
a Grade based on criteria from the World Health Organization (WHO).
b N=699-974; all patients with laboratory or non-laboratory data.
c N=161-241; all pancreatic cancer patients with laboratory or non-laboratory data.
d N=979.
e Regardless of causality.
f Table includes non-laboratory data with incidence for all patients ≥ 10%. For approximately 60% of the patients, non-laboratory adverse reactions were graded only if assessed to be possibly drug-related.

Hematologic — In studies in pancreatic cancer myelosuppression is the dose-limiting toxicity with Gemzar (gemcitabine hcl) , but < 1% of patients discontinued therapy for either anemia, leukopenia, or thrombocytopenia. Red blood cell transfusions were required by 19% of patients. The incidence of sepsis was less than 1%. Petechiae or mild blood loss (hemorrhage), from any cause, was reported in 16% of patients; less than 1% of patients required platelet transfusions. Patients should be monitored for myelosuppression during Gemzar (gemcitabine hcl) therapy and dosage modified or suspended according to the degree of hematologic toxicity [see DOSAGE AND ADMINISTRATION].

Gastrointestinal — Nausea and vomiting were commonly reported (69%) but were usually of mild to moderate severity. Severe nausea and vomiting (WHO Grade 3/4) occurred in < 15% of patients. Diarrhea was reported by 19% of patients, and stomatitis by 11% of patients.

Hepatic — In clinical trials, Gemzar (gemcitabine hcl) was associated with transient elevations of one or both serum transaminases in approximately 70% of patients, but there was no evidence of increasing hepatic toxicity with either longer duration of exposure to Gemzar (gemcitabine hcl) or with greater total cumulative dose. Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving Gemzar (gemcitabine hcl) alone or in combination with other potentially hepatotoxic drugs [see ADVERSE REACTIONS].

Renal— In clinical trials, mild proteinuria and hematuria were commonly reported. Clinical findings consistent with the Hemolytic Uremic Syndrome (HUS) were reported in 6 of 2429 patients (0.25%) receiving Gemzar (gemcitabine hcl) in clinical trials. Four patients developed HUS on Gemzar (gemcitabine hcl) therapy, 2 immediately posttherapy. The diagnosis of HUS should be considered if the patient develops anemia with evidence of microangiopathic hemolysis, elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or evidence of renal failure (elevation of serum creatinine or BUN). Gemzar (gemcitabine hcl) therapy should be discontinued immediately. Renal failure may not be reversible even with discontinuation of therapy and dialysis may be required [see ADVERSE REACTIONS].

Fever — The overall incidence of fever was 41%. This is in contrast to the incidence of infection (16%) and indicates that Gemzar (gemcitabine hcl) may cause fever in the absence of clinical infection. Fever was frequently associated with other flu-like symptoms and was usually mild and clinically manageable.

Rash — Rash was reported in 30% of patients. The rash was typically a macular or finely granular maculopapular pruritic eruption of mild to moderate severity involving the trunk and extremities. Pruritus was reported for 13% of patients.

Pulmonary — In clinical trials, dyspnea, unrelated to underlying disease, has been reported in association with Gemzar (gemcitabine hcl) therapy. Dyspnea was occasionally accompanied by bronchospasm. Pulmonary toxicity has been reported with the use of Gemzar (gemcitabine hcl) [see ADVERSE REACTIONS]. The etiology of these effects is unknown. If such effects develop, Gemzar (gemcitabine hcl) should be discontinued. Early use of supportive care measures may help ameliorate these conditions.

Edema — Edema (13%), peripheral edema (20%), and generalized edema ( < l%) were reported. Less than 1% of patients discontinued due to edema.

Flu-like Symptoms — "Flu syndrome" was reported for 19% of patients. Individual symptoms of fever, asthenia, anorexia, headache, cough, chills, and myalgia were commonly reported. Fever and asthenia were also reported frequently as isolated symptoms. Insomnia, rhinitis, sweating, and malaise were reported infrequently. Less than 1% of patients discontinued due to flu-like symptoms.

Infection — Infections were reported for 16% of patients. Sepsis was rarely reported ( < 1%).

Alopecia — Hair loss, usually minimal, was reported by 15% of patients.

Neurotoxicity — There was a 10% incidence of mild paresthesias and a < 1% rate of severe paresthesias.

Extravasation — Injection-site related events were reported for 4% of patients. There were no reports of injection site necrosis. Gemzar (gemcitabine hcl) is not a vesicant.

Allergic — Bronchospasm was reported for less than 2% of patients. Anaphylactoid reaction has been reported rarely. Gemzar (gemcitabine hcl) should not be administered to patients with a known hypersensitivity to this drug [see CONTRAINDICATIONS].

Cardiovascular — During clinical trials, 2% of patients discontinued therapy with Gemzar (gemcitabine hcl) due to cardiovascular events such as myocardial infarction, cerebrovascular accident, arrhythmia, and hypertension. Many of these patients had a prior history of cardiovascular disease [see ADVERSE REACTIONS].

Combination Use in Non-Small Cell Lung Cancer

In the Gemzar (gemcitabine hcl) plus cisplatin versus cisplatin study, dose adjustments occurred with 35% of Gemzar (gemcitabine hcl) injections and 17% of cisplatin injections on the combination arm, versus 6% on the cisplatin-only arm. Dose adjustments were required in greater than 90% of patients on the combination, versus 16% on cisplatin. Study discontinuations for possibly drug-related adverse reactions occurred in 15% of patients on the combination arm and 8% of patients on the cisplatin arm. With a median of 4 cycles of Gemzar (gemcitabine hcl) plus cisplatin treatment, 94 of 262 patients (36%) experienced a total of 149 hospitalizations due to possibly treatment-related adverse reactions. With a median of 2 cycles of cisplatin treatment, 61 of 260 patients (23%) experienced 78 hospitalizations due to possibly treatment-related adverse reactions.

In the Gemzar (gemcitabine hcl) plus cisplatin versus etoposide plus cisplatin study, dose adjustments occurred with 20% of Gemzar (gemcitabine hcl) injections and 16% of cisplatin injections in the Gemzar (gemcitabine hcl) plus cisplatin arm compared with 20% of etoposide injections and 15% of cisplatin injections in the etoposide plus cisplatin arm. With a median of 5 cycles of Gemzar (gemcitabine hcl) plus cisplatin treatment, 15 of 69 patients (22%) experienced 15 hospitalizations due to possibly treatment-related adverse reactions. With a median of 4 cycles of etoposide plus cisplatin treatment, 18 of 66 patients (27%) experienced 22 hospitalizations due to possibly treatment-related adverse reactions. In patients who completed more than one cycle, dose adjustments were reported in 81% of the Gemzar (gemcitabine hcl) plus cisplatin patients, compared with 68% on the etoposide plus cisplatin arm. Study discontinuations for possibly drug-related adverse reactions occurred in 14% of patients on the Gemzar (gemcitabine hcl) plus cisplatin arm and in 8% of patients on the etoposide plus cisplatin arm. The incidence of myelosuppression was increased in frequency with Gemzar (gemcitabine hcl) plus cisplatin treatment (~90%) compared to that with the Gemzar (gemcitabine hcl) monotherapy (~60%). With combination therapy Gemzar (gemcitabine hcl) dosage adjustments for hematologic toxicity were required more often while cisplatin dose adjustments were less frequently required.

Table 5 presents the safety data from the Gemzar (gemcitabine hcl) plus cisplatin versus cisplatin study in non-small cell lung cancer. The NCI Common Toxicity Criteria (CTC) were used. The two-drug combination was more myelosuppressive with 4 (1.5%) possibly treatment-related deaths, including 3 resulting from myelosuppression with infection and one case of renal failure associated with pancytopenia and infection. No deaths due to treatment were reported on the cisplatin arm. Nine cases of febrile neutropenia were reported on the combination therapy arm compared to 2 on the cisplatin arm. More patients required RBC and platelet transfusions on the Gemzar (gemcitabine hcl) plus cisplatin arm.

Myelosuppression occurred more frequently on the combination arm, and in 4 possibly treatment-related deaths myelosuppression was observed. Sepsis was reported in 4% of patients on the Gemzar (gemcitabine hcl) plus cisplatin arm compared to 1% on the cisplatin arm. Platelet transfusions were required in 21% of patients on the combination arm and < ]% of patients on the cisplatin arm. Hemorrhagic events occurred in 14% of patients on the combination arm and 4% on the cisplatin arm. However, severe hemorrhagic events were rare. Red blood cell transfusions were required in 39% of the patients on the Gemzar (gemcitabine hcl) plus cisplatin arm, versus 13% on the cisplatin arm. The data suggest cumulative anemia with continued Gemzar (gemcitabine hcl) plus cisplatin use.

Nausea and vomiting despite the use of antiemetics occurred more often with Gemzar (gemcitabine hcl) plus cisplatin therapy (78%) than with cisplatin alone (71%). In studies with single-agent Gemzar (gemcitabine hcl) , a lower incidence of nausea and vomiting (58% to 69%) was reported. Renal function abnormalities, hypomagnesemia, neuromotor, neurocortical, and neurocerebellar toxicity occurred more often with Gemzar (gemcitabine hcl) plus cisplatin than with cisplatin monotherapy. Neurohearing toxicity was similar on both arms.

Cardiac dysrrhythmias of Grade 3 or greater were reported in 7 (3%) patients treated with Gemzar (gemcitabine hcl) plus cisplatin compared to one ( < 1%) Grade 3 dysrrhythmia reported with cisplatin therapy. Hypomagnesemia and hypokalemia were associated with one Grade 4 arrhythmia on the Gemzar (gemcitabine hcl) plus cisplatin combination arm.

Table 6 presents data from the randomized study of Gemzar (gemcitabine hcl) plus cisplatin versus etoposide plus cisplatin in 135 patients with NSCLC. One death (1.5%) was reported on the Gemzar (gemcitabine hcl) plus cisplatin arm due to febrile neutropenia associated with renal failure which was possibly treatment-related. No deaths related to treatment occurred on the etoposide plus cisplatin arm. The overall incidence of Grade 4 neutropenia on the Gemzar (gemcitabine hcl) plus cisplatin arm was less than on the etoposide plus cisplatin arm (28% versus 56%). Sepsis was experienced by 2% of patients on both treatment arms. Grade 3 anemia and Grade 3/4 thrombocytopenia were more common on the Gemzar (gemcitabine hcl) plus cisplatin arm. RBC transfusions were given to 29% of the patients who received Gemzar (gemcitabine hcl) plus cisplatin versus 21% of patients who received etoposide plus cisplatin. Platelet transfusions were given to 3% of the patients who received Gemzar (gemcitabine hcl) plus cisplatin versus 8% of patients who received etoposide plus cisplatin. Grade 3/4 nausea and vomiting were also more common on the Gemzar (gemcitabine hcl) plus cisplatin arm. On the Gemzar (gemcitabine hcl) plus cisplatin arm, 7% of participants were hospitalized due to febrile neutropenia compared to 12% on the etoposide plus cisplatin arm. More than twice as many patients had dose reductions or omissions of a scheduled dose of Gemzar (gemcitabine hcl) as compared to etoposide, which may explain the differences in the incidence of neutropenia and febrile neutropenia between treatment arms. Flu syndrome was reported by 3% of patients on the Gemzar (gemcitabine hcl) plus cisplatin arm with none reported on the comparator arm. Eight patients (12%) on the Gemzar (gemcitabine hcl) plus cisplatin arm reported edema compared to one patient (2%) on the etoposide plus cisplatin arm.

Table 5: Selected CTC-Graded Adverse Reactions From Comparative Trial of Gemzar (gemcitabine hcl) Plus Cisplatin Versus Single-Agent Cisplatin in NSCLC
CTC Grades (% incidence)a

  Gemzar plus Cisplatinb Cisplatinc
  All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4
Laboratoryd
Hemato logic            
  Anemia 89 22 3 67 6 1
  RBC Transfusione 39     13    
  Leukopenia 82 35 11 25 2 1
  Neutropenia 79 22 35 20 3 1
  Thrombocytopenia 85 25 25 13 3 1
  Platelet Transfusionse 21     < 1    
  Lymphocytes 75 25 18 51 12 5
Hepatic
  Transaminase 22 2 1 10 1 0
  Alkaline Phosphatase 19 1 0 13 0 0
Renal
  Proteinuria 23 0 0 18 0 0
  Hematuria 15 0 0 13 0 0
  Creatinine 38 4 < 1 31 2 < 1
Other Laboratory
  Hyperglycemia 30 4 0 23 3 0
  Hypomagnesemia 30 4 3 17 2 0
  Hypocalcemia 18 2 0 7 0 < 1
Non-laboratoryf
  Nausea 93 25 2 87 20 < 1
  Vomiting 78 11 12 71 10 9
  Alopecia 53 1 0 33 0 0
  Neuro Motor 35 12 0 15 3 0
  Neuro Hearing 25 6 0 21 6 0
  Diarrhea 24 2 2 13 0 0
  Neuro Sensory 23 1 0 18 1 0
  Infection 18 3 2 12 1 0
  Fever 16 0 0 5 0 0
  Neuro Cortical 16 3 1 9 1 0
  Neuro Mood 16 1 0 10 1 0
  Local 15 0 0 6 0 0
  Neuro Headache 14 0 0 7 0 0
  Stomatitis 14 1 0 5 0 0
  Hemorrhage 14 1 0 4 0 0
  Dyspnea 12 4 3 11 3 2
  Hypotension 12 1 0 7 1 0
  Rash 11 0 0 3 0 0
a Grade based on Common Toxicity Criteria (CTC). Table includes data for adverse reactions with incidence ≥ 10% in either arm.
b N=217-253; all Gemzar (gemcitabine hcl) plus cisplatin patients with laboratory or non-laboratory data. Gemzar (gemcitabine hcl) at 1000 mg/m2 on Days 1, 8, and 15 and cisplatin at 100 mg/m2 on Day 1 every 28 days.
c N=213-248; all cisplatin patients with laboratory or non-laboratory data. Cisplatin at 100 mg/m2 on Day 1 every 28 days.
d Regardless of causality.
e Percent of patients receiving transfusions. Percent transfusions are not CTC-graded events.
f Non-laboratory events were graded only if assessed to be possibly drug-related.

Table 6: Selected WHO-Graded Adverse Reactions From Comparative Trial of Gemzar (gemcitabine hcl) Plus Cisplatin Versus Etoposide Plus Cisplatin in NSCLC
WHO Grades (% incidence)a

  Gemzar plus Cisplatinb Cisplatinc
  All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4
Laboratoryd
  Hematologic            
  Anemia 88 22 0 77 13 2
  RBC Transfusionse 29     21    
  Leukopenia 86 26 3 87 36 7
  Neutropenia 88 36 28 87 20 56
  Thrombocytopenia 81 39 16 45 8 5
  Platelet Transfusionse 3     8    
Hepatic
  ALT 6 0 0 12 0 0
  AST 3 0 0 11 0 0
  Alkaline Phosphatase 16 0 0 11 0 0
  Bilirubin 0 0 0 0 0 0
Renal
  Proteinuria 12 0 0 5 0 0
  Hematuria 22 0 0 10 0 0
  BUN 6 0 0 4 0 0
  Creatinine 2 0 0 2 0 0
Non-laboratoryf,g
  Nausea and Vomiting 96 35 4 86 19 7
  Fever 6 0 0 3 0 0
  Rash 10 0 0 3 0 0
  Dyspnea 1 0 1 3 0 0
  Diarrhea 14 1 1 13 0 2
  Hemorrhage 9 0 3 3 0 3
  Infection 28 3 1 21 8 0
  Alopecia 77 13 0 92 51 0
  Stomatitis 20 4 0 18 2 0
  Somnolence 3 0 0 3 2 0
  Paresthesias 38 0 0 16 2 0
a Grade based on criteria from the World Health Organization (WHO).
b N=67-69; all Gemzar (gemcitabine hcl) plus cisplatin patients with laboratory or non-laboratory data. Gemzar (gemcitabine hcl) at 1250 mg/m2 on Days 1 and 8 and cisplatin at 100 mg/m2 on Day 1 every 21 days.
c N=57-63; all cisplatin plus etoposide patients with laboratory or non-laboratory data. Cisplatin at 100 mg/m2 on Day 1 and intravenous etoposide at 100 mg/m2 on Days 1, 2, and 3 every 21 days.
d Regardless of causality.
e Percent of patients receiving transfusions. Percent transfusions are not WHO-graded events.
f Non-laboratory events were graded only if assessed to be possibly drug-related.
g Pain data were not collected.

Combination Use in Breast Cancer

In the Gemzar (gemcitabine hcl) plus paclitaxel versus paclitaxel study, dose reductions occurred with 8% of Gemzar (gemcitabine hcl) injections and 5% of paclitaxel injections on the combination arm, versus 2% on the paclitaxel arm. On the combination arm, 7% of Gemzar (gemcitabine hcl) doses were omitted and < 1% of paclitaxel doses were omitted, compared to < 1% of paclitaxel doses on the paclitaxel arm. A total of 18 patients (7%) on the Gemzar (gemcitabine hcl) plus paclitaxel arm and 12 (5%) on the paclitaxel arm discontinued the study because of adverse reactions. There were two deaths on study or within 30 days after study drug discontinuation that were possibly drug-related, one on each arm.

Table 7 presents the safety data occurrences of ≥ 10% (all grades) from the Gemzar (gemcitabine hcl) plus paclitaxel versus paclitaxel study in breast cancer.

Table 7: Adverse Reactions From Comparative Trial of Gemzar (gemcitabine hcl) Plus Paclitaxel Versus Single-Agent Paclitaxel in Breast Cancera
CTC Grades (% incidence)

  Gemzar plus Paclitaxel
(N=262)
Paclitaxel
(N=259)
All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4
Laboratoryb
Hematologic            
  Anemia 69 6 1 51 3 < 1
  Neutropenia 69 31 17 31 4 7
  Thrombocytopenia 26 5 < 1 7 < 1 < 1
  Leukopenia 21 10 1 12 2 0
Hepatobiliary
  ALT 18 5 < 1 6 < 1 0
  AST 16 2 0 5 < 1 0
Non-laboratoryc
  Alopecia 90 14 4 92 19 3
  Neuropathy-sensory 64 5 < 1 58 3 0
  Nausea 50 1 0 31 2 0
  Fatigue 40 6 < 1 28 1 < 1
  Myalgia 33 4 0 33 3 < 1
  Vomiting 29 2 0 15 2 0
  Arthralgia 24 3 0 22 2 < 1
  Diarrhea 20 3 0 13 2 0
  Anorexia 17 0 0 12 < 1 0
  Neuropathy-motor 15 2 < 1 10 < 1 0
  Stomatitis/pharyngitis 13 1 < 1 8 < 1 0
  Fever 13 < 1 0 3 0 0
  Rash/desquamation 11 < 1 < 1 5 0 0
a Grade based on Common Toxicity Criteria (CTC) Version 2.0 (all grades ≥ 10%).
b Regardless of causality.
c Non-laboratory events were graded only if assessed to be possibly drug-related.

The following are the clinically relevant adverse reactions that occurred in > 1% and < 10% (all grades) of patients on either arm. In parentheses are the incidences of Grade 3 and 4 adverse reactions (Gemzar (gemcitabine hcl) plus paclitaxel versus paclitaxel): febrile neutropenia (5.0% versus 1.2%), infection (0.8% versus 0.8%), dyspnea (1.9% versus 0), and allergic reaction/hypersensitivity (0 versus 0.8%).

No differences in the incidence of laboratory and non-laboratory events were observed in patients 65 years or older, as compared to patients younger than 65.

Combination Use in Ovarian Cancer

In the Gemzar (gemcitabine hcl) plus carboplatin versus carboplatin study, dose reductions occurred with 10.4% of Gemzar (gemcitabine hcl) injections and 1.8% of carboplatin injections on the combination arm, versus 3.8% on the carboplatin alone arm. On the combination arm, 13.7% of Gemzar (gemcitabine hcl) doses were omitted and 0.2% of carboplatin doses were omitted, compared to 0% of carboplatin doses on the carboplatin alone arm. There were no differences in discontinuations due to adverse reactions between arms (10.9% versus 9.8%, respectively).

Table 8 presents the adverse reactions (all grades) occurring in ≥ 10% of patients in the ovarian cancer study.

Table 8: Adverse Reactions From Comparative Trial of Gemzar (gemcitabine hcl) Plus Carboplatin Versus Single-Agent Carboplatin in Ovarian Cancera
CTC Grades (% incidence)

  Gemzar plus Carboplatin
(N=175)
Carboplatin
(N=174)
  All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4
Laboratoryb            
  Hematologic            
  Neutropenia 90 42 29 58 11 1
  Anemia 86 22 6 75 9 2
  Leukopenia 86 48 5 70 6 < 1
  Thrombocytopenia 78 30 5 57 10 1
  RBC Transfusionsc 38     15    
  Platelet Transfusionsc 9     3    
Non-laboratoryb
  Nausea 69 6 0 61 3 0
  Alopecia 49 0 0 17 0 0
  Vomiting 46 6 0 36 2 < 1
  Constipation 42 6 1 37 3 0
  Fatigue 40 3 < 1 32 5 0
  Neuropathy-sensory 29 1 0 27 2 0
  Diarrhea 25 3 0 14 < 1 0
  Stomatitis/pharyngitis 22 < 1 0 13 0 0
  Anorexia 16 1 0 13 0 0
a Grade based on Common Toxicity Criteria (CTC) Version 2.0 (all grades ≥ 10%).
b Regardless of causality.
c Percent of patients receiving transfusions. Transfusions are not CTC-graded events. Blood transfusions included both packed red blood cells and whole blood.

In addition to blood product transfusions as listed in Table 8, myelosuppression was also managed with hematopoietic agents. These agents were administered more frequently with combination therapy than with monotherapy (granulocyte growth factors: 23.6% and 10.1%, respectively; erythropoietic agents: 7.3% and 3.9%, respectively).

The following are the clinically relevant adverse reactions, regardless of causality, that occurred in > 1% and < 10% (all grades) of patients on either arm. In parentheses are the incidences of Grade 3 and 4 adverse reactions (Gemzar (gemcitabine hcl) plus carboplatin versus carboplatin): AST or ALT elevation (0 versus 1.2%), dyspnea (3.4% versus 2.9%), febrile neutropenia(l.l% versus 0), hemorrhagic event (2.3% versus 1.1%), hypersensitivity reaction (2.3% versus 2.9%), motor neuropathy (1.1% versus 0.6%), and rash/desquamation (0.6% versus 0).

No differences in the incidence of laboratory and non-laboratory events were observed in patients 65 years or older, as compared to patients younger than 65.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Gemzar (gemcitabine hcl) . 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.

These adverse reactions have occurred after Gemzar (gemcitabine hcl) single-agent use and Gemzar (gemcitabine hcl) in combination with other cytotoxic agents. Decisions to include these events are based on the seriousness of the event, frequency of reporting, or potential causal connection to Gemzar (gemcitabine hcl) .

Cardiovascular Congestive heart failure and myocardial infarction have been reported very rarely with the use of Gemzar (gemcitabine hcl) . Arrhythmias, predominantly supraventricular in nature, have been reported very rarely.

Vascular Disorders — Clinical signs of peripheral vasculitis and gangrene have been reported very rarely.

Skin Cellulitis and non-serious injection site reactions in the absence of extravasation have been rarely reported. Severe skin reactions, including desquamation and bullous skin eruptions, have been reported very rarely.

Hepatic — Increased liver function tests including elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GOT), alkaline phosphatase, and bilirubin levels have been reported rarely. Serious hepatotoxicity including liver failure and death has been reported very rarely in patients receiving Gemzar (gemcitabine hcl) alone or in combination t with other potentially hepatotoxic drugs. Hepatic veno-occlusive disease has been reported.

Pulmonary — Parenchyma! toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported rarely following one or more doses of Gemzar (gemcitabine hcl) administered to patients with various malignancies. Some patients experienced the onset of pulmonary symptoms up to 2 weeks after the last Gemzar (gemcitabine hcl) dose. Respiratory failure and death occurred very rarely in some patients despite discontinuation of therapy.

Renal— Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar (gemcitabine hcl) . Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.

Injury, Poisoning, and Procedural ComplicationsRadiation recall reactions have been reported [see WARNINGS AND PRECAUTIONS].

Read the Gemzar (gemcitabine hcl) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No specific drug interaction studies have been conducted. Information is available on the pharmacodynamics and pharmacokinetics of Gemzar (gemcitabine hcl) in combination with cisplatin, paclitaxel, or carboplatin [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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

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].

Hematology

Gemzar (gemcitabine hcl) can suppress bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia [see ADVERSE REACTIONS], and myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy [see DOSAGE AND ADMINISTRATION].

Pulmonary

Pulmonary toxicity has been reported with the use of Gemzar (gemcitabine hcl) . In cases of severe lung toxicity, Gemzar (gemcitabine hcl) therapy should be discontinued immediately and appropriate supportive care measures instituted [see ADVERSE REACTIONS].

Renal

Hemolytic Uretnic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar (gemcitabine hcl) . 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].

Gemzar (gemcitabine hcl) 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].

Hepatic

Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar (gemcitabine hcl) alone or in combination with other potentially hepatotoxic drugs [see ADVERSE REACTIONS].

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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].

Pregnancy

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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].

Laboratory Tests

Patients receiving Gemzar (gemcitabine hcl) 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].

Laboratory evaluation of renal and hepatic function should be performed prior to initiation of therapy and periodically thereafter [see DOSAGE AND ADMINISTRATION].

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 (gemcitabine hcl) .

Non-concurrent (given > 7 days apart)Analysis of the data does not indicate enhanced toxicity when Gemzar (gemcitabine hcl) is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) has radiosensitizing activity. Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of Gemzar (gemcitabine hcl) , frequency of Gemzar (gemcitabine hcl) administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. In a single trial, where Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) administered at lower doses with concurrent radiotherapy has predictable and less severe toxicity. However, the optimum regimen for safe administration of Gemzar (gemcitabine hcl) with therapeutic doses of radiation has not yet been determined in all tumor types.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Gemzar (gemcitabine hcl) have not been conducted. Gemcitabine induced forward mutations in vitro in a mouse lymphoma (L5178Y) assay and was clastogenic in an in vivo mouse micronucleus assay. Gemcitabine was negative when tested using the Ames, in vivo sister chromatid exchange, and in vitro chromosomal aberration assays, and did not cause unscheduled DNA synthesis in vitro. Gemcitabine IP doses of 0.5 mg/kg/day (about 1/700 the human dose on a mg/m2 basis) in male mice had an effect on fertility with moderate to severe hypospermatogenesis, decreased fertility, and decreased implantations. In female mice, fertility was not affected but maternal toxicities were observed at 1.5 mg/kg/day administered intravenously (about 1/200 the human dose on a mg/m2 basis) and fetotoxicity or embryolethality was observed at 0.25 mg/kg/day administered intravenously (about 1/1300 the human dose on a mg/m2 basis).

Use In Specific Populations

Pregnancy

Pregnancy Category D. See 'WARNINGS and PRECAUTIONS' section.

Gemzar (gemcitabine hcl) can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, Gemzar (gemcitabine hcl) is expected to result in adverse reproductive effects. There are no adequate and well-controlled studies of Gemzar (gemcitabine hcl) in pregnant women. - Gemcitabine is embryotoxic causing fetal malformations (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day in mice (about 1/200 the recommended human dose on a mg/m2 basis). Gemcitabine is fetotoxic causing fetal malformations (fused pulmonary artery, absence of gall bladder) at doses of 0.1 mg/kg/day in rabbits (about 1/600 the recommended human dose on a mg/m2 basis). Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. If this 1 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 WARNINGS AND PRECAUTIONS].

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Gemzar (gemcitabine hcl) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Gemzar (gemcitabine hcl) in pediatric patients has not been established. Gemzar (gemcitabine hcl) was evaluated in a Phase 1 trial in pediatric patients with refractory leukemia and determined that the maximum tolerated dose was 10 mg/m2/min for 360 minutes three times weekly followed by a one-week rest period. Gemzar (gemcitabine hcl) was also evaluated in a Phase 2 trial in patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) using 10 mg/m2/min for 360 minutes three times weekly followed by a one-week rest period. Toxicities observed included bone marrow suppression, febrile neutropenia, elevation of serum transaminases, nausea, and rash/desquamation, which were similar to those reported in adults. No meaningful clinical activity was observed in this Phase 2 trial.

Geriatric Use

Gemzar clearance is affected by age [see CLINICAL PHARMACOLOGY]. There is no evidence, however, that unusual dose adjustments [see DOSAGE AND ADMINISTRATION] are necessary in patients over 65, and in general, adverse reaction rates in the single-agent safety database of 979 patients were similar in patients above and below 65. Grade 3/4 thrombocytopenia was more common in the elderly. In the randomized clinical trial of Gemzar (gemcitabine hcl) in combination with carboplatin for recurrent ovarian cancer [see Clinical Studies], 125 women treated with Gemzar (gemcitabine hcl) plus carboplatin were < 65 years and 50 were ≥ 65 years. Similar effectiveness was observed between older and younger women. There was significantly higher Grade 3/4 neutropenia in women 65 years of age or older. Overall, there were no other substantial differences in toxicity profile of Gemzar (gemcitabine hcl) plus carboplatin based on age.

Renal

Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of Gemzar (gemcitabine hcl) . 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].

Gemzar (gemcitabine hcl) 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 WARNINGS AND PRECAUTIONS].

Hepatic

Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving Gemzar (gemcitabine hcl) alone or in combination with other potentially hepatotoxic drugs [see ADVERSE REACTIONS].

Gemzar (gemcitabine hcl) 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 (gemcitabine hcl) 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 WARNINGS AND PRECAUTIONS].

Gender

Gemzar clearance is affected by gender [see CLINICAL PHARMACOLOGY]. In the single-agent safety database (N=979 patients), however, there is no evidence that unusual dose adjustments [see DOSAGE AND ADMINISTRATION] are necessary in women. In general, in single-agent studies of Gemzar (gemcitabine hcl) , adverse reaction rates were similar in men and women, but women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3/4 neutropenia and thrombocytopenia. There was a greater tendency in women, especially older women, not to proceed to the next cycle.

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There is no known antidote for overdoses of Gemzar (gemcitabine hcl) . Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5700 mg/m2 was administered by intravenous infusion over 30 minutes every 2 weeks to several patients in a Phase 1 study. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.

CONTRAINDICATIONS

Gemzar (gemcitabine hcl) is contraindicated in those patients with a known hypersensitivity to the drug.

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Gemcitabine exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and also blocking the progression of cells through the Gl/S-phase boundary. Gemcitabine is metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic effect of gemcitabine is attributed to a combination of two actions of the diphosphate and the triphosphate nucleosides, which leads to inhibition of DNA synthesis. First, gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. Inhibition of this enzyme by the diphosphate nucleoside causes a reduction in the concentrations of deoxynucleotides, including dCTP. Second, gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP (by the action of the diphosphate) enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands. After this addition, there is inhibition of further DNA synthesis. DNA polymerase epsilon is unable to remove the gemcitabine nucleotide and repair the growing DNA strands (masked chain termination). In CEM T lymphoblastoid cells, gemcitabine induces internucleosomal DNA fragmentation, one of the characteristics of programmed cell death.

Pharmacodynamics

Gemcitabine demonstrated dose-dependent synergistic activity with cisplatin in vitro. No effect of cisplatin on gemcitabine triphosphate accumulation or DNA double-strand breaks was observed. In vivo, gemcitabine showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 orNCI-H520 xenografts. Gemcitabine was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to gemcitabine 4 hours before cisplatin produced the greatest interaction.

Pharmacokinetics

Absorption and Distribution

The pharmacokinetics of gemcitabine were examined in 353 patients, with various solid tumors. Pharmacokirietic parameters were derived using data from patients treated for varying durations of therapy given weekly with periodic rest weeks and using both short infusions ( < 70 minutes) and long infusions (70 to 285 minutes). The total Gemzar (gemcitabine hcl) dose varied from 500 to 3600 mg/m2.

The volume of distribution was increased with infusion length. Volume of distribution of gemcitabine was 50 L/m2 following infusions lasting < 70 minutes. For long infusions, the volume of distribution rose to 370 L/m2.

Gemcitabine pharmacokinetics are linear and are described by a 2-compartment model. Population pharmacokinetic analyses of combined single and multiple dose studies showed that the volume of distribution of gemcitabine was significantly influenced by duration of infusion and gender. Gemcitabine plasma protein binding is negligible.

Metabolism

Gemcitabine disposition was studied in 5 patients who received a single 1000 mg/m2/30 minute infusion of radiolabeled drug. Within one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine ( < 10%) and the inactive uracil metabolite, 2'-deoxy-2',2'-difluorouridine (dFdU), accounted for 99% of the excreted dose. The metabolite dFdU is also found in plasma.

The active metabolite, gemcitabine triphosphate, can be extracted from peripheral blood mononuclear cells. The half-life of the terminal phase for gemcitabine triphosphate from mononuclear cells ranges from 1.7 to 19.4 hours.

Excretion

Clearance of gemcitabine was affected by age and gender. The lower clearance in women and the elderly results in higher concentrations of gemcitabine for any given dose. Differences in either clearance or volume of distribution based on patient characteristics or the duration of infusion result in changes in half-life and plasma concentrations. Table 9 shows plasma clearance and half-life of gemcitabine following short infusions for typical patients by age and gender.

Table 9: Gemcitabine Clearance and Half-Life for the "Typical" Patient

Age Clearance Men
(L/hr/m2)
Clearance Women
(L/hr/m2)
Half-Lifea Men (min) Half-Lifea Women (min)
29 92.2 69.4 42 49
45 75.7 57.0 48 57
65 55.1 41.5 61 73
79 40.7 30.7 79 94
a Half-life for patients receiving a short infusion ( < 70 min).

Gemcitabine half-life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions.

Drug Interactions

When Gemzar (gemcitabine hcl) (1250 mg/m2 on Days 1 and 8) and cisplatin (75 mg/m2 on Day 1) were administered in NSCLC patients, the clearance of gemcitabine on Day 1 was 128 L/hr/m2 and on Day 8 was 107 L/hr/m2. The clearance of cisplatin in the same study was reported to be 3.94 mL/min/m2 with a corresponding half-life of 134 hours [see DRUG INTERACTIONS]. Analysis of data from metastatic breast cancer patients shows that, on average, Gemzar (gemcitabine hcl) has little or no effect on the pharmacokinetics (clearance and half-life) of paclitaxel and paclitaxel has little or no effect on the pharmacokinetics of Gemzar (gemcitabine hcl) . Data from NSCLC patients demonstrate that Gemzar (gemcitabine hcl) and carboplatin given in combination does not alter the pharmacokinetics of Gemzar (gemcitabine hcl) or carboplatin compared to administration of either single-agent. However, due to wide confidence intervals and small sample size, interpatient variability may be observed.

Clinical Studies

Ovarian Cancer

Gemzar (gemcitabine hcl) was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized to receive either Gemzar (gemcitabine hcl) 1000 mg/m2 on Days 1 and 8 of a 21-day cycle and carboplatin AUC 4 administered after Gemzar (gemcitabine hcl) on Day 1 of each cycle or single-agent carboplatin AUC 5 administered on Day 1 of each 21-day cycle as the control arm. The primary endpoint of this study was progression free survival (PFS).

Patient characteristics are shown in Table 10. The addition of Gemzar (gemcitabine hcl) to carboplatin resulted in statistically significant improvement in PFS and overall response rate as shown in Table 11 and Figure 1. Approximately 75% of patients in each arm received poststudy chemotherapy. Only 13 of 120 patients with documented poststudy chemotherapy regimen in the carboplatin arm received Gemzar (gemcitabine hcl) after progression. There was not a significant difference in overall survival between arms.

Table 10: Gemzar (gemcitabine hcl) Plus Carboplatin Versus Carboplatin in Ovarian Cancer - Baseline Demographics and Clinical Characteristics

  Gemzar/Carboplatin Carboplatin
Number of randomized patients 178 178
Median age, years Range 59 36 to 78 58 21 to 81
Baseline ECOG performance status 0-la 94% 95%
Disease Status
  Evaluable 7.9% 2.8%
  Bidimensionally measurable 91.6% 95.5%
Platinum-free intervalb
  6-12 months 39.9% 39.9%
   > 12 months 59.0% 59.6%
First-line therapy
  Platinum-taxane combination 70.2% 71.3%
  Platinum-non-taxane combination 28.7% 27.5%
  Platinum monotherapy 1.1% 1.1%
a Nine patients (5 on the Oemzar plus carboplatm arm and 4 on the carboplatin arm) did not have baseline bastern Cooperative Oncology Group (ECOG) performance status recorded.
b Three patients (2 on the Gemzar (gemcitabine hcl) plus carboplatin arm and 1 on the carboplatin arm) had a platinum-free interval of less than 6 months.

Table 11: Gemzar (gemcitabine hcl) Plus Carboplatin Versus Carboplatin in Ovarian Cancer- Results of Efficacy Analysis

  Gemzar/Carboplatin
(N=178)
Carboplatin
(N=178)
 
PFS
  Median (95%, C.I.) months 8.6 (8.0, 9.7) 5.8(5.2,7.1) p=0.0038d
  Hazard Ratio (95%, C.I.) 0.72 (0.57, 0.90)  
  Overall Survival
  Median (95%, C.I.) months 18.0 (16.2,20.3) 17.3(15.2, 19.3) p=0.8977d
  Hazard Ratio (95%, C.l.) Ratio 0.98 (0.78, 1.24)  
  Adjusteda Hazard Ratio (95%, C.I.) 0.86 (0.67, 1.10)  
Investigator Reviewed
  Overall Response Rate 47.2% 30.9% p=0.0016e
  CR 14.6% 6.2%  
  PR+PRNMb 32.6% 24.7%  
Independently Reviewed
  Overall Response Ratec,f 46.3% 35.6% p=0.11e
  CR 9.1% 4.0%  
  PR+PRNM 37.2% 31.7%  
a Treatment adjusted for performance status, tumor area, and platinum-free interval.
b Partial response non-measurable disease
c Independent reviewers could not evaluate disease demonstrated by sonography or physical exam.
d Log Rank, unadjusted
e Chi Square
f Independently reviewed cohort - Gemzar (gemcitabine hcl) /Carboplatin N= 121, Carboplatin N= 101

Figure 1: Kaplan-Meier Curve of Progression Free Survival in Gemzar (gemcitabine hcl) Plus Carboplatin Versus Carboplatin in Ovarian Cancer (N=356)

Kaplan-Meier Curve of Progression Free Survival in Gemzar Plus Carboplatin - Illustration

Breast Cancer

Data from a multi-national, randomized Phase 3 study (529 patients) support the use of Gemzar (gemcitabine hcl) in combination with paclitaxel for treatment of breast cancer patients who have received prior adjuvant/neoadjuvant anthracycline chemotherapy unless clinically contraindicated. Gemzar (gemcitabine hcl) 1250 mg/m2 was administered on Days 1 and 8 of a 21-day cycle with paclitaxel 175 mg/m2 administered prior to Gemzar (gemcitabine hcl) on Day 1 of each cycle. Single-agent paclitaxel 175 mg/m2 was administered on Day 1 of each 21-day cycle as the control arm.

The addition of Gemzar (gemcitabine hcl) to paclitaxel resulted in statistically significant improvement in time to documented disease progression and overall response rate compared to monotherapy with paclitaxel as shown in Table 12 and Figure 2. Final survival analysis results at 440 events were Hazard Ratio of 0.86 (95%, CI: 0.71 - 1.04) for the ITT population, as shown in Table 12.

Table 12: Gemzar (gemcitabine hcl) Plus Paclitaxel Versus Paclitaxel in Breast Cancer

  Gemzar/Paclitaxel Paclitaxel  
Number of patients 267 262  
Median age, years Range 53 26 to 83 52 26 to 75  
Metastatic disease 97.0% 96.9%  
Baseline KPSa ≥ 90 70.4% 74.4%  
Number of tumor sites
  1-2 56.6% 58.8%  
   ≥ 3 43.4% 41.2%  
Visceral disease 73.4% 72.9%  
Prior anthracycline 96.6% 95.8%  
Overall Survivalb
  Median (95%, CI) 18.6 (16.5,20.7) 15.8 (14.1, 17.3)  
  Hazard Ratio (95%, CI) 0.86 (0.71,1.04)  
Time to Documented Disease Progressionc
  Median (95%, C.I.), months 5.2 (4.2, 5.6) 2.9 (2.6, 3.7) p < 0.000l
  Hazard Ratio (95%, C.I.) 0.650 (0.524, 0.805) p < 0.000l
  Overall Response Rate0 (95%, C.I.) 40.8% (34.9, 46.7) 22.1% (17.1, 27.2) p < 0.000l
a Karnofsky Performance Status.
b Based on the ITT population
c These represent reconciliation of investigator and Independent Review Committee assessments according to a predefined algorithm.

Figure 2: Kaplan-Meier Curve of Time to Documented Disease Progression in Gemzar (gemcitabine hcl) Plus Paclitaxel Versus Paclitaxel Breast Cancer Study (N=529)

Kaplan-Meier Curve of Time to Documented Disease Progression in Gemzar Plus Paclitaxel - Illustration

Non-Small Cell Lung Cancer (NSCLC)

Data from 2 randomized clinical studies (657 patients) support the use of Gemzar (gemcitabine hcl) in combination with cisplatin for the first-line treatment of patients with locally advanced or metastatic NSCLC.

Gemzar (gemcitabine hcl) plus cisplatin versus cisplatin: This study was conducted in Europe, the US, and Canada in 522 patients with inoperable Stage III A, IIIB, or IV NSCLC who had not received prior chemotherapy. Gemzar (gemcitabine hcl) 1000 mg/m2 was administered on Days 1, 8, and 15 of a 28-day cycle with cisplatin 100 mg/m2 administered on Day 1 of each cycle. Single-agent cisplatin 100 mg/m2 was administered on Day 1 of each 28-day cycle. The primary endpoint was survival. Patient demographics are shown in Table 13. An imbalance with regard to histology was observed with 48% of patients on the cisplatin arm and 37% of patients on the Gemzar (gemcitabine hcl) plus cisplatin arm having adenocarcinoma.

The Kaplan-Meier survival curve is shown in Figure 3. Median survival time on the Gemzar (gemcitabine hcl) plus cisplatin arm was 9.0 months compared to 7.6 months on the single-agent cisplatin arm (Log rank p=0.008, two-sided). Median time to disease progression was 5.2 months on the Gemzar (gemcitabine hcl) plus cisplatin arm compared to 3.7 months on the cisplatin arm (Log rank p=0.009, two-sided). The objective response rate on the Gemzar (gemcitabine hcl) plus cisplatin arm was 26% compared to 10% with cisplatin (Fisher's Exact p < 0.0001, two-sided). No difference between treatment arms with regard to duration of response was observed.

Gemzar (gemcitabine hcl) plus cisplatin versus etoposide plus cisplatin: A second, multicenter, study in Stage IIIB or IV NSCLC randomized 135 patients to Gemzar (gemcitabine hcl) 1250 mg/m2 on Days 1 and 8, and cisplatin 100 mg/m2 on Day 1 of a 21-day cycle or to intravenous etoposide 100 mg/m2 on Days 1, 2, and 3 and cisplatin 100 mg/m2 on Day 1 of a 21-day cycle (Table 13).

There was no significant difference in survival between the two treatment arms (Log rank p=0.18, two-sided). The median survival was 8.7 months for the Gemzar (gemcitabine hcl) plus cisplatin arm versus 7.0 months for the etoposide plus cisplatin arm. Median time to disease progression for the Gemzar (gemcitabine hcl) plus cisplatin arm was 5.0 months compared to 4.1 months on the etoposide plus cisplatin arm (Log rank p=0.015, two-sided). The objective response rate for the Gemzar (gemcitabine hcl) plus cisplatin arm was 33% compared to 14% on the etoposide plus cisplatin arm (Fisher's Exact p=0.01, two-sided).

Figure 3: Kaplan-Meier Survival Curve in Gemzar (gemcitabine hcl) Plus Cisplatin Versus Cisplatin NSCLC Study (N=522)

Kaplan-Meier Survival Curve in Gemzar Plus Cisplatin Versus Cisplatin NSCLC Study - Illustration

Table 13: Randomized Trials of Combination Therapy With Gemzar (gemcitabine hcl) Plus Cisplatin in NSCLC

Trial 28-day Schedulea 21-day Scheduleb
Treatment Arm Gemzar/Cisplatin Cisplatin   Gemzar/Cisplatin Cisplatin/Etoposide  
Number of patients 260 262   69 66  
  Male 182 186   64 61  
  Female 78 76   5 5  
Median age, years 62 63   58 60  
Range 36 to 88 35 to 79   33 to 76 35 to 75  
Stage IIIA 7% 7%   N/Ac N/Ac  
Stage IIIB 26% 23%   48% 52%  
Stage IV 67% 70%   52% 49%  
Baseline KPSd 70 to 80 41% 44%   45% 52%  
Baseline KPSd 90 to 100 57% 55%   55% 49%  
Survival     p=0.008     p=0.18
  Median, months 9.0 7.6   8.7 7.0  
  (95%, C.I.) months 8.2, 11.0 6.6, 8.8   7.8, 10.1 6.0, 9.7  
Time to Disease Progression     p=0.009     p=0.015
  Median, months 5.2 3.7   5.0 4.1  
  (95%, C.I.) months 4.2, 5.7 3.0,4.3   4.2, 6.4 2.4, 4.5  
Tumor Response 26% 10% p < 0.0001e 33% 14% p=0.01e
a 28-day schedule — Gemzar (gemcitabine hcl) plus Cisplatin: Gemzar (gemcitabine hcl) 1000 mg/m2 on Days 1, 8, and 15 and cisplatin 100 mg/m on Day 1 every 28 days; Single-agent cisplatin: cisplatin 100 mg/m2 on Day 1 every 28 days.
b 21-day schedule — Gemzar (gemcitabine hcl) plus cisplatin: Gemzar (gemcitabine hcl) 1250 mg/m2 on Days 1 and 8 and cisplatin 100 mg/m2 on Day 1 every 21 days; Etoposide plus Cisplatin: cisplatin 100 mg/m2 on Day 1 and intravenous etoposide 100 mg/m2 on Days 1, 2, and 3 every 21 days.
c N/A Not applicable.
d Karnofsky Performance Status.
e p-value for tumor response was calculated using the two-sided Fisher's Exact test for difference in binomial proportions. All other p-values were calculated using the Log rank test for difference in overall time to an event.

Pancreatic Cancer

Data from 2 clinical trials evaluated the use of Gemzar (gemcitabine hcl) in patients with locally advanced or metastatic pancreatic cancer. The first trial compared Gemzar (gemcitabine hcl) to 5-Fluorouracil (5-FU) in patients who had received no prior chemotherapy. A second trial studied the use of Gemzar (gemcitabine hcl) injjapcreatic cancer patients previously treated with 5-FU or a 5-FU-containing regimen. In both studies, the first cycle of Gemzar (gemcitabine hcl) was administered intravenously at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitated holding a dose) followed by a week of rest from treatment with Gemzar (gemcitabine hcl) . Subsequent cycles consisted of injections once weekly for 3 consecutive weeks out of every 4 weeks.

The primary efficacy parameter in these studies was "clinical benefit response," which is a measure of clinical improvement based on analgesic consumption, pain intensity, performance status, and weight change. Definitions for improvement in these variables were formulated prospectively during the design of the 2 trials. A patient was considered a clinical benefit responder if either:

i) the patient showed a ≥ 50% reduction in pain intensity (Memorial Pain Assessment Card) or analgesic consumption, or a 20-point or greater improvement in performance status (Karnofsky Performance Status) for a period of at least 4 consecutive weeks, without showing any sustained worsening in any of the other parameters. Sustained worsening was defined as 4 consecutive weeks with either any increase in pain intensity or analgesic consumption or a 20-point decrease in performance status occurring during the first 12 weeks of therapy.
OR:
ii) the patient was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain ( ≥ 7% increase maintained for ≥ 4 weeks) not due to fluid accumulation.

The first study was a multicenter (17 sites in US and Canada), prospective, single-blinded, two-arm, randomized, comparison of Gemzar (gemcitabine hcl) and 5-FU in patients with locally advanced or metastatic pancreatic cancer who had received no prior treatment with chemotherapy. 5-FU was administered intravenously at a weekly dose of 600 mg/m2 for 30 minutes. The results from this randomized trial are shown in Table 14. Patients treated with Gemzar (gemcitabine hcl) had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to 5-FU. The Kaplan-Meier curve for survival is shown in Figure 4. No confirmed objective tumor responses were observed with either treatment.

Table 14: Gemzar (gemcitabine hcl) Versus 5-FU in Pancreatic Cancer

  Gemzar 5-FU  
Number of patients 63 63  
  Male 34 34  
  Female 29 29  
Median age 62 years 61 years  
  Range 37 to 79 36 to 77  
Stage IV disease 71.4% 76.2%  
Baseline KPSa ≤ 70 69.8% 68.3%  
 
Clinical benefit response 22.2% (Nc=14) 4.8% (Nc=3) p=0.004e
Survival     p=0.0009
  Median 5.7 months 4.2 months  
  6-month probabilityb (N=30) 46% (N=19)29%  
  9-month probabilityb (N=14)24% (N=4) 5%  
  1-year probabilityb (N=9) 1 8% (N=2) 2%  
  Range 0.2 to 18.6 months 0.4 to 1 5. l+d months  
  95% C.I. of the median 4.7 to 6.9 months 3.1 to 5.1 months  
Time to Disease Progression     p=0.0013
  Median 2.1 months 0.9 months  
  Range 0.1 +d to 9.4 months 0.1 to 12.0+d months  
  95% C.I. of the median 1.9 to 3. 4 months 0.9 to 1.1 months  
a Karnofsky Performance Status.
b Kaplan-Meier estimates.
c N=number of patients.
d No progression at last visit; remains alive.
e The p-value for clinical benefit response was calculated using the two-sided test for difference in binomial proportions. All other p-values were calculated using the Log rank test for difference in overall time to an event.

Clinical benefit response was achieved by 14 patients treated with Gemzar (gemcitabine hcl) and 3 patients treated with 5-FU. One patient on the Gemzar (gemcitabine hcl) arm showed improvement in all 3 primary parameters (pain intensity, analgesic consumption, and performance status). Eleven patients on the Gemzar (gemcitabine hcl) arm and 2 patients on the 5-FU arm showed improvement in analgesic consumption and/or pain intensity with stable performance status. Two patients on the Gemzar (gemcitabine hcl) arm showed improvement in analgesic consumption or pain intensity with improvement in performance status. One patient on the 5-FU arm was stable with regard to pain intensity and analgesic consumption with improvement in performance status. No patient on either arm achieved a clinical benefit response based on weight gain.

Figure 4: Kaplan-Meier Survival Curve

Kaplan-Meier Survival Curve - Illustration

The second trial was a multicenter (17 US and Canadian centers), open-label study of Gemzar (gemcitabine hcl) in 63 patients with advanced pancreatic cancer previously treated with 5-FU or a 5-FU-containing regimen. The study showed a clinical benefit response rate of 27% and median survival of 3.9 months.

Other Clinical Studies

When Gemzar (gemcitabine hcl) was administered more frequently than once weekly or with infusions longer than 60 minutes, increased toxicity was observed. Results of a Phase 1 study of Gemzar (gemcitabine hcl) to assess the maximum tolerated dose (MTD) on a daily x 5 schedule showed that patients developed significant hypotension and severe flu-like symptoms that were intolerable at doses above 10 mg/m2. The incidence and severity of these events were dose-related. Other Phase 1 studies using a twice-weekly schedule reached MTDs of only 65 mg/m2 (30-minute infusion) and 150 mg/m2 (5-minute bolus). The dose-limiting toxicities were thrombocytopenia and flu-like symptoms, particularly asthenia. In a Phase 1 study to assess the maximum tolerated infusion time, clinically significant toxicity, defined as myelosuppression, was seen with weekly doses of 300 mg/m2 at or above a 270-minute infusion time. The half-life of gemcitabine is influenced by the length of the infusion and the toxicity appears to be increased if Gemzar (gemcitabine hcl) is administered more frequently than once weekly or with infusions longer than 60 minutes [see WARNINGS AND PRECAUTIONS].

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.ISA, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs: Am J Health-Syst Pharm. 2006;63:1172-1193.

4. Polovich, M., White, J. M, & Kelleher, L. O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Low Blood Cells Counts

Patients should be adequately informed of the risk of low blood cell counts and instructed to immediately contact their physician should any sign of infection develop including fever. Patients should also contact their physician if bleeding or symptoms of anemia occur [see WARNINGS AND PRECAUTIONS].

Pregnancy

There are no adequate and well-controlled studies of Gemzar (gemcitabine hcl) in pregnant women. Based on animal studies Gemzar (gemcitabine hcl) can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the risks to the fetus need to be discussed with their physician [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Gemzar (gemcitabine hcl) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see Use In Specific Populations].

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Low Blood Cells Counts

Patients should be adequately informed of the risk of low blood cell counts and instructed to immediately contact their physician should any sign of infection develop including fever. Patients should also contact their physician if bleeding or symptoms of anemia occur [see WARNINGS AND PRECAUTIONS].

Pregnancy

There are no adequate and well-controlled studies of Gemzar (gemcitabine hcl) in pregnant women. Based on animal studies Gemzar (gemcitabine hcl) can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the risks to the fetus need to be discussed with their physician [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Gemzar (gemcitabine hcl) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see Use In Specific Populations].

Last reviewed on RxList: 4/4/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Gemzar Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

GEMCITABINE - INJECTION

(gem-SITE-uh-bean)

COMMON BRAND NAME(S): Gemzar

USES: Gemcitabine is used alone or with other treatments/medications to treat certain types of cancer (including breast, lung, ovarian, pancreatic). It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat certain other cancers, such as bladder cancer.

HOW TO USE: This medication is given by injection into a vein by a healthcare professional, usually over 30 minutes once a week or as directed by your doctor. The dosage is based on your medical condition and response to therapy.

If this medication touches your skin, wash the skin immediately and completely with soap and water.

Disclaimer

Gemzar Consumer (continued)

SIDE EFFECTS: Nausea, vomiting, diarrhea, pain/redness at the injection site, and flu-like symptoms (e.g., fever, muscle aches) may occur. Nausea and vomiting can be severe. In some cases, drug therapy may be needed to prevent or relieve nausea and vomiting. Changes in diet and lifestyle, such as eating several small meals or limiting activity, may help lessen some of these effects. If any of these effects persist or worsen, contact your doctor or pharmacist promptly.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: dizziness, fainting, mouth sores, numbness/tingling of hands/feet, swelling of ankles/feet, severe stomach/abdominal pain, easy bleeding/bruising, cough, difficulty catching your breath (shortness of breath, wheezing), unusual tiredness, fast/irregular heartbeat, change in amount of urine, dark urine, yellowing of the eyes/skin.

Get medical help right away if any of these rare but very serious side effects occur: chest pain, jaw/left arm pain, weakness on one side of the body, slurred speech, vision changes, confusion.

This medication can lower your ability to fight an infection (bone marrow depression). Notify your doctor promptly if you develop any signs of infection (e.g., high fever, chills, persistent sore throat).

An allergic reaction to this drug is unlikely, but get medical help right away if it occurs. Symptoms of a serious allergic reaction include: rash, itching/swelling (especially of the face/tongue/throat), dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Gemzar (gemcitabine hcl) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using gemcitabine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bone marrow problems (e.g., leukopenia, thrombocytopenia, anemia), heart problems (e.g., irregular heartbeat, heart failure), kidney problems, liver problems, radiation therapy.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine.

Wash your hands well to prevent the spread of infections.

To lower the chance of getting cut, bruised or injured, use caution with sharp objects like safety razors or nail cutters, and avoid activities such as contact sports. Use a soft-bristle toothbrush to lessen the risk of bleeding gums.

This medication is not recommended for use during pregnancy. Consult your doctor for more details and to discuss reliable forms of birth control. It is recommended that men and women use two effective forms of birth control (e.g., condoms and birth control pills) while taking this medication and for some time afterwards.

It is not known whether this medication passes into breast milk. Because of the potential harm to the nursing infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Disclaimer

Gemzar Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Laboratory and/or medical tests (e.g., complete blood counts before each dose, kidney function tests, liver function tests) should be performed from time to time to monitor for side effects and response to treatment. Consult your doctor for more details. Keep all scheduled medical appointments.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule.

STORAGE: Not applicable. This medication is given in a clinic and will not be stored at home.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised September 2010. Copyright(c) 2010 First Databank, Inc.

Gemzar Patient Information Including Side Effects

Brand Names: Gemzar

Generic Name: gemcitabine (Pronunciation: jem SYE ta been)

What is gemcitabine (Gemzar)?

Gemcitabine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Gemcitabine is used to treat cancers of the pancreas, lung and breast.

Gemcitabine may also be used for purposes not listed in this medication guide.

What are the possible side effects of gemcitabine (Gemzar)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • pale skin, easy bruising or bleeding, unusual weakness;
  • urinating less than usual or not at all;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • sudden severe headache, confusion, problems with vision, speech, or balance;
  • fever, chills, body aches, flu symptoms;
  • white patches or sores inside your mouth or on your lips;
  • pain, swelling, or skin changes where the needle was placed;
  • hearing problems;
  • blood in your urine; or
  • breathing problems.

Less serious side effects may include:

  • mild nausea, vomiting, upset stomach;
  • diarrhea or constipation;
  • swelling in your hands, ankles, or feet;
  • skin rash;
  • numbness or tingly feeling;
  • drowsiness; or
  • hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Gemzar (gemcitabine hcl) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about gemcitabine (Gemzar)?

Gemcitabine is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Gemcitabine is usually given once a week for several weeks. The medicine must be given slowly, and the IV infusion can take up to 30 minutes to complete.

Gemcitabine can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. Your kidney and liver function may also need to be checked. Do not miss any scheduled visits to your doctor.

Do not receive a "live" vaccine while you are being treated with gemcitabine, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

If any of this medicine accidentally gets on your skin, wash the area thoroughly with soap and warm water.

Side Effects Centers

Gemzar Patient Information including How Should I Take

What should I discuss with my healthcare provider before receiving gemcitabine (Gemzar)?

You should not use this medication if you are allergic to gemcitabine.

To make sure you can safely use gemcitabine, tell your doctor if you have any of these other conditions:

  • kidney disease;
  • liver disease; or
  • if you are receiving radiation treatment.

FDA pregnancy category D. Do not use gemcitabine if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether gemcitabine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using gemcitabine.

How is gemcitabine used (Gemzar)?

Gemcitabine is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. The medicine must be given slowly, and the IV infusion can take up to 30 minutes to complete.

Gemcitabine is usually given once a week for up to 7 weeks.

Gemcitabine can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Visit your doctor regularly.

If any of this medicine accidentally gets on your skin, wash the area thoroughly with soap and warm water.

Side Effects Centers

Gemzar Patient Information including If I Miss a Dose

What happens if I miss a dose (Gemzar)?

Contact your doctor if you miss a miss an appointment to receive your gemcitabine infusion.

What happens if I overdose (Gemzar)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include numbness or tingly feeling, severe skin rash, fever, chills, flu symptoms, or any signs of infection.

What should I avoid while using gemcitabine (Gemzar)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using gemcitabine, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

What other drugs will affect gemcitabine (Gemzar)?

There may be other drugs that can interact with gemcitabine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about gemcitabine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 4.01. Revision date: 9/13/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers

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