Gemcitabine is a chemotherapy drug that is given as a treatment for some types of cancer. It is most commonly used to treat non-small cell lung cancer, pancreatic, bladder and breast cancer. This information describes gemcitabine, how it is given and some of its possible side effects.

What gemcitabine looks like

Gemcitabine is a colourless fluid.

How it is given

Gemcitabine may be given:

• as a drip (infusion) through a fine tube (cannula) inserted into a vein, over a short period of time
• through a central line, which is inserted under the skin into a vein near the collarbone, or a PICC line inserted into a vein in the crook of your arm.
• The infusion usually takes about 30 minutes.

Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated.

Possible side effects

Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given gemcitabine, and may be different if you are having more than one chemotherapy drug.

We have outlined the most common side effects and some of the less common ones, so that you can be aware of them if they occur. However, we have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects which you think may be due to the drug, but which are not listed in this information, please discuss them with your doctor or chemotherapy nurse.

Lowered resistance to infection

Gemcitabine can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given, and your resistance to infection usually reaches its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily, and will usually have returned to normal levels before your next course of chemotherapy is due.

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy, to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.

Bruising or bleeding

Gemcitabine can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, and bleeding gums. You platelet count will be checked frequently.

Anaemia (low number of red blood cells)

While having treatment with gemcitabine you may become anaemic. This may make you feel pale, tired and short of breath on exertion. Let your doctor or nurse know if these effects are a problem, as you may need iron tablets or a blood transfusion.

Feeling sick (nausea) and being sick (vomiting)

If you do feel sick this may begin a few hours after the treatment is given and last for up to a day. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective.

Loss of appetite

This is usually mild and may last a day or so. A dietitian or specialist nurse at your hospital can give advice and tips on maintaining weight.

Temporary effect on liver function

Gemcitabine may cause changes in the way that your liver works, though your liver will return to normal when the treatment is finished. You are very unlikely to notice any problems but your doctor will check your liver is working properly before each treatment.

Change in kidney function

Some people have a small amount of blood or protein in their urine when it is tested. You are very unlikely to notice any change and it is rarely causes any harm. Your kidney function is measured in blood tests.

Skin changes

Gemcitabine can cause a rash, which may be itchy. Your doctor can prescribe medicines to relieve the symptoms. You may also notice some swelling of your ankles. This is usually mild and goes away after the treatment ends.

Flu-like illness

Occasionally a flu-like illness may occur with gemcitabine. You may have headaches, aching joints and muscles and a high temperature. You should always let your doctor know about a high temperature immediately.

Fluid retention

This may cause swelling of the ankles or breathlessness. Let your doctor know if you notice this effect.

Tiredness and feeling weak

It is important to allow yourself plenty of time to rest.

 

Less common side effects

Sore mouth and ulcers

Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help reduce the risk of this happening. Tell your doctor if you have any of these problems, as special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.

Taste changes

You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.

Breathlessness

Rarely, gemcitabine can cause temporary breathlessness. Contact your doctor if you feel breathless.

Diarrhoea

This can usually be easily controlled with medicine such as imodium (loperamide), but tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you do have diarrhoea.

Constipation

This can usually be managed by eating a high fibre diet and drinking plenty of fluids.

Hair loss

It is rare for gemcitabine to make all your hair fall out, but this may occasionally happen. More commonly your hair may just thin. Hair loss is temporary and your hair will regrow once the treatment ends.

 

Additional information

Gemcitabine may cause drowsiness. Take care if you are driving or operating machinery following this treatment.

Risk of blood clots

Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood.

Other medicines

Some medicines can be harmful to take when you are having chemotherapy. Tell your doctor about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility

Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.

Contraception

It is not advisable to become pregnant or father a child while taking gemcitabine, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.

 

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ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS

ADVERSE REACTIONS SIGNIFICANT

>10%:

• Cardiovascular: Peripheral edema (20%), edema (13%)
• Central nervous system: Pain (10% to 48%), fever (30% to 41%), somnolence (5% to 11%)
• Dermatologic: Rash (24% to 30%), alopecia (15% to 18%), pruritus (13%)
• Gastrointestinal: Nausea/vomiting (64% to 71%; grades 3/4: 1% to 13%), constipation (10% to 31%), diarrhea (19% to 30%), stomatitis (10% to 14%)
• Hematologic: Anaemia (65% to 73%; grade 4: 1% to 3%), leukopenia (62% to 71%; grade 4: =1%), neutropenia (61% to 63%; grade 4: 6% to 7%), thrombocytopenia (24% to 47%; grade 4: =1%), hemorrhage (4% to 17%; grades 3/4: <1% to 2%); myelosuppression is the dose-limiting toxicity
• Hepatic: Transaminases increased (67% to 78%; grades 3/4: 1% to 12%), alkaline phosphatase increased (55% to 77%; grades 3/4: 2% to 16%), bilirubin increased (13% to 26%; grades 3/4: <1% to 6%)
• Renal: Proteinuria (10% to 45%; grades 3/4: <1%), hematuria (13% to 35%; grades 3/4: <1%), BUN increased (8% to 16%; grades 3/4: 0%)
• Respiratory: Dyspnea (6% to 23%)
• Miscellaneous: Flu-like syndrome (19%), infection (8% to 16%; grades 3/4: <1% to 2%)

1% to 10%:

• Local: Injection site reactions (4%)
• Neuromuscular & skeletal: Paresthesia (2% to 10%)
• Renal: Creatinine increased (2% to 8%)
• Respiratory: Bronchospasm (<2%)

<1% (Limited to important or life-threatening; reported with single-agent use or with combination therapy, all reported rarely):

Adult respiratory distress syndrome, anaphylactoid reaction, anorexia, arrhythmias, bullous skin eruptions, cellulitis, cerebrovascular accident, CHF, chills, cough, desquamation, diaphoresis, gangrene, GGT increased, headache, hemolytic uremic syndrome (HUS), hepatotoxic reaction (rare), hypertension, insomnia, interstitial pneumonitis, liver failure, malaise, MI, peripheral vasculitis, petechiae, pulmonary edema, pulmonary fibrosis, radiation recall, renal failure, respiratory failure, rhinitis, sepsis, supraventricular arrhythmia, weakness

MECHANISM OF ACTION

A pyrimidine antimetabolite that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase, specific for the S-phase of the cycle. Gemcitabine is phosphorylated intracellularly by deoxycytidine kinase to gemcitabine monophosphate, which is further phosphorylated to active metabolites gemcitabine diphosphate and gemcitabine triphosphate. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase; gemcitabine triphosphate incorporates into DNA and inhibits DNA polymerase.

PHARMACODYNAMICS / KINETICS

• Distribution: Infusions <70 minutes: 50 L/m2; Long infusion times: 370 L/m2
• Protein binding: Low
• Metabolism: Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites
• Half-life elimination:
  • Gemcitabine: Infusion time =1 hour: 42-94 minutes; infusion time 3-4 hours: 4-10.5 hours
  • Metabolite (gemcitabine triphosphate), terminal phase: 1.7-19.4 hours
• Time to peak, plasma: 30 minutes after completion of infusion
• Excretion: Urine (92% to 98%; primarily as inactive uracil metabolite); faeces (<1%)