Gemcitabine Accord (Gemcitabine)

What Is Gemcitabine Accord and What Is It Used For?

Quick Answer: Gemcitabine Accord is a chemotherapy medicine belonging to the class of cytotoxic agents called nucleoside analogues. It kills cancer cells by disrupting their DNA replication and is used to treat non-small cell lung cancer, pancreatic cancer, breast cancer, ovarian cancer, and bladder cancer.

Gemcitabine Accord contains the active ingredient gemcitabine (as gemcitabine hydrochloride), a synthetic nucleoside analogue structurally related to deoxycytidine. It belongs to the class of antimetabolite chemotherapy drugs — agents that interfere with the essential metabolic processes cancer cells need to grow and divide. Once administered intravenously, gemcitabine is taken up by cells and phosphorylated intracellularly to two active metabolites: gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP). These metabolites disrupt DNA synthesis through a dual mechanism that makes gemcitabine particularly effective against rapidly proliferating tumor cells.

Gemcitabine diphosphate inhibits ribonucleotide reductase, an enzyme critical for producing the deoxynucleotide building blocks required for DNA synthesis. By depleting the intracellular pool of deoxynucleotides, this action starves cancer cells of the raw materials they need to replicate their DNA. Simultaneously, gemcitabine triphosphate is incorporated directly into the growing DNA strand in place of the natural nucleotide deoxycytidine triphosphate. Once incorporated, it causes what is known as “masked chain termination” — the DNA strand cannot continue to elongate normally, leading to cell death (apoptosis).

Gemcitabine may be given as a single agent or in combination with other chemotherapy drugs, depending on the cancer type and the goals of treatment. The approved indications include:

• Non-small cell lung cancer (NSCLC): Gemcitabine is used alone or in combination with cisplatin as first-line treatment for patients with locally advanced or metastatic NSCLC. The gemcitabine-cisplatin combination is one of several platinum-based doublet regimens recommended by the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) for this indication.
• Pancreatic cancer: Gemcitabine monotherapy has been a cornerstone of treatment for locally advanced or metastatic pancreatic adenocarcinoma since the landmark trial by Burris and colleagues (1997) demonstrated improved clinical benefit over fluorouracil. It remains a standard first-line option, particularly for patients who are not candidates for more intensive combination regimens such as FOLFIRINOX or gemcitabine plus nab-paclitaxel.
• Breast cancer: In combination with paclitaxel, gemcitabine is used for the treatment of unresectable locally recurrent or metastatic breast cancer in patients who have relapsed after prior adjuvant or neoadjuvant anthracycline-containing chemotherapy, unless anthracyclines were clinically contraindicated.
• Ovarian cancer: Gemcitabine in combination with carboplatin is used for the treatment of patients with locally advanced or metastatic epithelial ovarian cancer that has relapsed after a treatment-free interval of at least 6 months following initial platinum-based therapy (platinum-sensitive relapse).
• Bladder cancer: In combination with cisplatin, gemcitabine is used for locally advanced or metastatic transitional cell carcinoma of the bladder. The gemcitabine-cisplatin regimen has demonstrated equivalent survival to the MVAC regimen (methotrexate, vinblastine, doxorubicin, cisplatin) with a more favorable toxicity profile.

Gemcitabine is listed on the World Health Organization (WHO) Model List of Essential Medicines, recognizing its critical importance in cancer treatment globally. The medication has been in clinical use since its initial approval in the late 1990s and has an extensive evidence base supporting its efficacy across multiple tumor types. Research continues into additional applications, including its use in biliary tract cancers, soft tissue sarcomas, and as a radiosensitizer in concurrent chemoradiation protocols.

What Should You Know Before Receiving Gemcitabine Accord?

Quick Answer: Do not receive gemcitabine if you are allergic to gemcitabine or any of its ingredients, or if you are breastfeeding. Blood tests for kidney function, liver function, and blood cell counts are required before each infusion. Inform your oncologist about all medical conditions and medications.

Contraindications

Gemcitabine Accord must not be used in the following situations:

• Hypersensitivity: You must not receive gemcitabine if you are allergic to gemcitabine or any of the other ingredients in this medicine (macrogol 300, propylene glycol, ethanol, sodium hydroxide, hydrochloric acid). If you have experienced an allergic reaction to gemcitabine in the past, inform your oncologist immediately.
• Breastfeeding: Gemcitabine is contraindicated during breastfeeding. The drug and its metabolites may pass into breast milk and cause serious harm to the nursing infant. Breastfeeding must be discontinued before starting gemcitabine treatment.

Warnings and Precautions

Before your first infusion and before each subsequent treatment cycle, your oncologist will order blood tests to assess whether your body can safely receive the next dose. These tests include a complete blood count (measuring white blood cells, red blood cells, and platelets), as well as kidney function tests and liver function tests. If your blood values are too low or your organ function is impaired, your doctor may decide to reduce the dose, delay treatment, or temporarily discontinue gemcitabine until your values recover.

Tell your doctor before starting treatment if any of the following apply to you:

• Previous severe skin reactions: If you have ever developed severe skin rash, skin peeling, blisters, or mouth sores while taking gemcitabine or any other medication, inform your doctor. Serious cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported with gemcitabine. These are rare but potentially life-threatening conditions that require immediate medical attention.
• Liver disease: Pre-existing liver disease may affect how your body processes gemcitabine and may increase the risk of liver-related complications during treatment. Your liver function will be closely monitored throughout therapy.
• Heart or vascular disease: Patients with cardiovascular conditions should be monitored carefully, as gemcitabine has been associated with cardiac events in rare cases, including heart failure and myocardial infarction.
• Kidney disease: Impaired kidney function may affect drug clearance and increase the risk of toxicity. Hemolytic uremic syndrome (HUS) — a serious condition involving destruction of red blood cells, low platelet counts, and acute kidney failure — has been reported with gemcitabine and can be fatal. Treatment must be discontinued immediately if HUS is suspected.
• Previous or planned radiation therapy: Gemcitabine can interact with radiation therapy, causing radiation recall reactions (inflammation in previously irradiated areas) or enhanced radiation toxicity. The timing of gemcitabine relative to radiation must be carefully planned by your oncology team.
• Recent vaccination: Live vaccines must not be administered during gemcitabine treatment because the drug suppresses the immune system, which could lead to serious or life-threatening infections from live vaccine strains.

Pregnancy, Breastfeeding, and Fertility

Gemcitabine must not be used during pregnancy unless absolutely necessary, as it may cause serious harm to the developing fetus. Preclinical studies have demonstrated teratogenic effects in animal models. Women of childbearing potential must use effective contraception during gemcitabine treatment and for at least 6 months after the last administered dose. If you become pregnant during treatment, inform your oncologist immediately so that the risks can be assessed.

Breastfeeding must be discontinued during gemcitabine therapy. It is not known whether gemcitabine is excreted in human breast milk, but given its mechanism of action, a risk to the breastfed infant cannot be excluded.

Men receiving gemcitabine are advised not to father a child during treatment and for at least 3 months after the last dose. Effective contraception should be used during this period. Because gemcitabine may impair fertility, men who wish to have children in the future should discuss sperm banking with their healthcare team before starting treatment.

Driving and Operating Machinery

Gemcitabine may cause drowsiness, particularly in patients who have consumed alcohol. The Gemcitabine Accord concentrate contains ethanol (alcohol) — up to 9.9 g per maximum daily dose, equivalent to approximately 250 ml of beer or 100 ml of wine. This alcohol content may impair your ability to drive or operate machinery. Do not drive or use machines until you are certain that gemcitabine treatment does not make you drowsy or otherwise impair your alertness.

Children and Adolescents

Gemcitabine is not recommended for use in patients under 18 years of age due to insufficient data on safety and efficacy in the pediatric population. If gemcitabine is being considered for a child or adolescent as part of a clinical trial or compassionate use program, this will be discussed in detail by the treating pediatric oncologist.

How Does Gemcitabine Interact with Other Drugs?

Quick Answer: Gemcitabine interacts with radiation therapy (risk of radiation recall and enhanced toxicity), live vaccines (risk of severe infection due to immunosuppression), and several chemotherapy agents. Always inform your oncologist about all medications, supplements, and recent vaccinations.

Because gemcitabine is a potent immunosuppressive and cytotoxic agent, drug interactions are an important clinical consideration. Your oncologist will carefully plan your treatment regimen to avoid harmful interactions while maximizing therapeutic benefit. Always inform your medical team about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and any vaccinations you have recently received or are planning to receive.

Clinically Significant Interactions

Additional Considerations

The interaction between gemcitabine and radiation therapy is particularly clinically important. Gemcitabine is a potent radiosensitizer, meaning it makes tissues more sensitive to the damaging effects of radiation. While this property is being investigated therapeutically in concurrent chemoradiation protocols for certain cancers, it also means that administering gemcitabine close in time to radiation therapy can cause severe toxicity to normal tissues. Radiation recall reactions — inflammatory reactions occurring in previously irradiated body areas when gemcitabine is administered later — have been documented weeks to years after the original radiation exposure.

Regarding combination chemotherapy, gemcitabine is commonly used together with cisplatin (for lung and bladder cancer), carboplatin (for ovarian cancer), and paclitaxel (for breast cancer). These are established, evidence-based combinations, but each carries additive toxicity risks that necessitate careful dose monitoring and potential dose adjustments. The sequence of drug administration within a combination regimen can also affect both efficacy and toxicity.

Patients on anticoagulant therapy (such as warfarin) should have their coagulation parameters monitored more frequently during gemcitabine treatment, as chemotherapy-related changes in liver function and platelet counts can alter the anticoagulant response. Inactivated vaccines may be administered during treatment but may produce a diminished immune response due to gemcitabine-induced immunosuppression.

What Is the Correct Dosage of Gemcitabine Accord?

Quick Answer: The recommended dose of gemcitabine is 1000–1250 mg per square meter of body surface area, given as a 30-minute intravenous infusion. The exact dose and schedule depend on the type of cancer being treated. Your oncologist calculates the dose based on your height and weight.

Gemcitabine is always administered by trained healthcare professionals in a hospital or clinic setting. You will not administer this medicine yourself. The dose is calculated based on your body surface area (BSA), which is determined by your height and weight. Your oncologist will adjust the dose or delay treatment based on your blood test results and overall condition.

Adults — Dosing by Cancer Type

How Gemcitabine Is Administered

The gemcitabine concentrate is diluted by pharmacy or nursing staff using sterile 0.9% sodium chloride solution before administration. The diluted solution is given through an intravenous infusion (drip) into a vein, typically over approximately 30 minutes. The infusion duration should not exceed 60 minutes, as longer infusion times have been associated with increased toxicity in clinical studies. You will be monitored during and after the infusion for any immediate reactions.

Children and Adolescents

Gemcitabine is not recommended for patients under 18 years of age. There is insufficient evidence regarding the safety and efficacy of gemcitabine in the pediatric population to support a dosing recommendation. Pediatric use may only be considered within the context of a clinical trial under specialist supervision.

Elderly Patients

No specific dose adjustment is recommended solely on the basis of age. However, elderly patients are more likely to have reduced bone marrow reserve, impaired organ function, and concurrent medications that may influence gemcitabine pharmacokinetics and toxicity. Gemcitabine tolerance is generally well documented in patients over 65 years of age, but careful monitoring is essential. Dose reductions may be required based on individual tolerability and blood count results.

Dose Modifications

Your oncologist will routinely review your blood test results before each gemcitabine infusion. Treatment may be delayed or the dose reduced if your blood counts are below acceptable thresholds. Specific dose reduction criteria are based on your absolute neutrophil count (ANC) and platelet count. In general:

• If ANC is below 500/mm³ or platelets are below 50,000/mm³, the infusion may be postponed until counts recover.
• For Grade 3–4 non-hematological toxicity (excluding nausea and vomiting), dose reduction or treatment delay is typical.
• Liver or kidney function deterioration may also necessitate dose modification at the discretion of your treating physician.

Overdose

What Are the Side Effects of Gemcitabine Accord?

Quick Answer: Very common side effects include low blood cell counts, nausea, vomiting, liver enzyme elevation, flu-like symptoms, rash, hair loss, shortness of breath, and edema. Serious but less common effects include heart attack, stroke, lung damage, kidney failure, and hemolytic uremic syndrome. Report any unusual symptoms to your oncology team immediately.

Like all chemotherapy medicines, gemcitabine can cause side effects, although not every patient experiences all of them. Because gemcitabine targets rapidly dividing cells, the most frequently affected tissues are bone marrow (which produces blood cells), the gastrointestinal lining, skin, and hair follicles. Most side effects are predictable, dose-related, and manageable with appropriate supportive care. Your oncology team will monitor you closely throughout treatment and adjust your therapy as needed.

Myelosuppression (bone marrow suppression leading to low blood cell counts) is the most clinically significant side effect of gemcitabine and the primary reason for dose modifications and treatment delays. Neutropenia (low white blood cells) increases infection risk, thrombocytopenia (low platelets) increases bleeding risk, and anemia (low red blood cells) causes fatigue and weakness. Your blood counts will be checked before each infusion, and your oncologist will adjust treatment accordingly.

Flu-like symptoms — including fever, chills, muscle aches, and general malaise — are very common, typically occurring within hours of the infusion. These symptoms are usually self-limiting and can be managed with paracetamol (acetaminophen). Nausea and vomiting are also very common but are generally well controlled with modern antiemetic medications that your medical team will prescribe.

Hepatotoxicity (liver damage) manifests primarily as elevated liver enzymes on blood tests and is usually transient and asymptomatic. However, in rare cases, serious liver damage including hepatic failure has been reported. Renal toxicity, including hemolytic uremic syndrome (HUS) and thrombotic microangiopathy (TMA), is uncommon but can be life-threatening. Any signs of worsening kidney function (decreased urine output, dark urine, swelling) should be reported to your medical team immediately.

Reporting Side Effects

If you experience any side effects, including any not listed above, talk to your doctor, pharmacist, or oncology nurse. You can also report suspected adverse reactions to your national pharmacovigilance authority. In the UK, reports can be made via the Yellow Card Scheme; in the US, through the FDA MedWatch program; and in the EU, through the national reporting systems listed on the EMA website. Reporting helps improve the safety information available for all patients.

How Should Gemcitabine Accord Be Stored?

Quick Answer: Gemcitabine Accord concentrate requires no special storage conditions. Each vial is for single use only. After dilution in 0.9% sodium chloride, the solution is stable for up to 60 days at 2–8°C or at 25°C, but should be used immediately for microbiological safety.

As Gemcitabine Accord is prepared and administered by healthcare professionals in a hospital or clinic, you will not typically handle or store this medication yourself. However, the following information is provided for completeness and for the benefit of healthcare professionals involved in preparation and administration.

• Unopened vials: No special storage conditions are required. Store out of the sight and reach of children.
• After opening (before dilution): Each vial is intended for single use and should be used immediately after opening. If not used immediately, storage conditions and times are the responsibility of the user.
• After dilution in 0.9% sodium chloride: The diluted solution is chemically and physically stable for 60 days at both 2–8°C and 25°C. However, from a microbiological standpoint, the solution should be used immediately. If not used immediately, in-use storage should not normally exceed 24 hours at 2–8°C, unless dilution has taken place under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the carton and vial after “EXP.” The expiry date refers to the last day of that month. Solutions containing PVC should be avoided, as DEHP may leach from PVC containers when storing prepared gemcitabine solutions. Equipment and containers that are PVC-free should be used for preparation, storage, and administration.

Any unused medicine or waste material should be disposed of in accordance with local requirements for cytotoxic drugs. Gemcitabine must never be disposed of through household waste or wastewater.

What Does Gemcitabine Accord Contain?

Quick Answer: Each ml of Gemcitabine Accord concentrate contains 100 mg of gemcitabine (as gemcitabine hydrochloride). Inactive ingredients include macrogol 300, propylene glycol, anhydrous ethanol, sodium hydroxide, and hydrochloric acid. Vial sizes range from 200 mg to 2000 mg of gemcitabine.

Understanding the complete composition of your medication is important, particularly for healthcare professionals involved in preparation and administration, and for patients with known allergies or sensitivities to specific ingredients.

Active Substance

The active pharmaceutical ingredient is gemcitabine, present as gemcitabine hydrochloride at a concentration of 100 mg/ml (expressed as gemcitabine). Gemcitabine (chemical name: 2′,2′-difluorodeoxycytidine, dFdC) is a fluorinated nucleoside analogue of deoxycytidine with potent antitumor activity. Vials are available containing 200 mg (2 ml), 1000 mg (10 ml), 1500 mg (15 ml), or 2000 mg (20 ml) of gemcitabine.

Inactive Ingredients (Excipients)

The excipients in Gemcitabine Accord serve as solvents, pH adjusters, and stabilizers for the concentrated solution:

• Macrogol 300 (polyethylene glycol 300) — co-solvent to maintain gemcitabine in solution
• Propylene glycol — co-solvent
• Anhydrous ethanol (44% w/v) — co-solvent. Contains a significant amount of alcohol; see warnings section for clinical implications
• Sodium hydroxide — pH adjustment
• Hydrochloric acid, concentrated — pH adjustment

Appearance and Packaging

Gemcitabine Accord concentrate for solution for infusion is a clear, colorless to slightly yellowish solution. It is supplied in clear glass vials sealed with a rubber stopper and aluminum flip-off cap. Available pack sizes include 1 × 2 ml vial (200 mg), 1 × 10 ml vial (1000 mg), 1 × 15 ml vial (1500 mg), and 1 × 20 ml vial (2000 mg). Not all pack sizes may be marketed in every country.

Marketing Authorization Holder and Manufacturer

The marketing authorization is held by Accord Healthcare B.V., Winthontlaan 200, 3526 KV Utrecht, Netherlands. Manufacturing sites include Accord Healthcare Polska Sp.z o.o. in Pabianice, Poland, and Accord Healthcare Single Member S.A. in Athens, Greece.