Consumer medicine information

DBL Gemcitabine Powder for Injection

Gemcitabine

BRAND INFORMATION

Brand name

DBL Gemcitabine Powder for Injection

Active ingredient

Gemcitabine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Gemcitabine Powder for Injection.

What is in this leaflet

This leaflet answers some common questions about DBL™ Gemcitabine for Injection. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given DBL™ Gemcitabine for Injection against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet.

You may need to read it again.

What DBL™ Gemcitabine for Injection is used for

This medicine is used to treat the following types of cancer:

  • lung cancer
  • pancreatic cancer
  • bladder cancer
  • breast cancer
  • ovarian cancer.

This medicine belongs to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear of these being called chemotherapy medicines.

This medicine works by killing cancer cells and stopping cancer cells from growing and multiplying.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

DBL™ Gemcitabine for Injection may be used alone or in combination with other medicines to treat cancer.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you are given DBL™ Gemcitabine for Injection

When you must not be given it

You must not be given DBL™ Gemcitabine for Injection if you have an allergy to:

  • any medicine containing gemcitabine hydrochloride
  • any of the ingredients listed at the end of this leaflet
  • if the packaging is torn or shows sign of tampering.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching, or hives on the skin.

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant.

Like most cytotoxic medicines, DBL™ Gemcitabine for Injection is not recommended for use during pregnancy. If there is any need to consider DBL™ Gemcitabine for Injection during your pregnancy, your doctor or pharmacist will discuss with you the benefits and risks of using it.

DBL™ Gemcitabine for Injection may cause birth defects if either the male or female is using it at the time of conception. It is recommended that you use some kind of birth control while you are being treated with DBL™ Gemcitabine for Injection.

Tell your doctor or pharmacist if you are breast-feeding while being treated with this medicine.

DBL™ Gemcitabine for Injection may pass into breast milk and there is a possibility that your baby may be affected.

You must not be given this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • liver problems
  • kidney problems.

If you have not told your doctor about any of the above, tell him/her before you are given DBL™ Gemcitabine for Injection.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

These medicines may be affected by DBL™ Gemcitabine for Injection, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while you are being treated with this medicine.

How DBL™ Gemcitabine for Injection is given

How much is given

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight, liver function, kidney function and other chemotherapy medicines you are being given.

DBL™ Gemcitabine for Injection may be given alone or in combination with other drugs.

Several courses of DBL™ Gemcitabine for Injection therapy may be needed depending on your response to treatment.

Additional treatment may not be repeated until your blood cell numbers return to acceptable levels and any uncontrolled effects have been controlled.

Ask your doctor if you want to know more about the dose of DBL™ Gemcitabine for Injection you receive.

How it is given

DBL™ Gemcitabine for Injection must only be given by a doctor or nurse.

This medicine is usually given as a slow injection into a vein over 30 minutes.

How often is it given

For Lung Cancer
DBL™ Gemcitabine for Injection can be given once a week for three consecutive weeks, followed by one week without treatment or once a week for two consecutive weeks, followed by one week without treatment. Your doctor will decide how many of these cycles you will need.

For Pancreatic Cancer
Initially, DBL™ Gemcitabine for Injection is given once a week for up to seven weeks followed by a week without treatment. Subsequent cycles of DBL™ Gemcitabine for Injection are given once a week for three consecutive weeks followed by a week without treatment. Your doctor will decide how many of these cycles you will need.

For Bladder Cancer
DBL™ Gemcitabine for Injection is given once a week for three consecutive weeks, followed by one week without treatment. Your doctor will decide how many of these cycles you will need.

For Breast Cancer
DBL™ Gemcitabine for Injection is given once a week for two consecutive weeks, followed by one week without treatment. Your doctor will decide how many of these cycles you will need.

For Ovarian Cancer
DBL™ Gemcitabine for Injection can be given once a week for two consecutive weeks, followed by one week without treatment. Your doctor will decide how many of these cycles you will need.

If you take too much (overdose)

As DBL™ Gemcitabine for Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any severe side effects after being given DBL™ Gemcitabine for Injection, tell your doctor immediately or go to Accident and Emergency at the nearest hospital.

In case of overdose, immediately contact the Poisons Information Centre for advice (telephone 13 11 26 in Australia, or call 0800 764 766 in New Zealand).

You may need urgent medical attention.

While you are being treated with DBL™ Gemcitabine for Injection

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given DBL™ Gemcitabine for Injection.

Tell any other doctors, dentists and pharmacists who treat you that you are being given this medicine.

If you become pregnant while being given this medicine, or soon after, tell your doctor immediately.

Keep all your doctor's appointments so your progress can be checked.

Your doctor may want to check your blood pressure and do some blood and other tests from time to time to check on your progress and to detect any unwanted side effects.

Keep follow up appointments with your doctor.

It is important to have your follow-up doses of DBL™ Gemcitabine for Injection at the appropriate times to get the best effects from your treatments.

Things to be careful of

Be careful driving or operating machinery until you know how DBL™ Gemcitabine for Injection affects you.

This medicine may cause sleepiness or drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery, or do anything else that could be dangerous.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being treated with DBL™ Gemcitabine for Injection.

Like other medicines that treat cancer, DBL™ Gemcitabine for Injection may have unwanted side effects, some of which may be serious. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • sleepiness, drowsiness
  • itchy rash
  • swelling of the hands, feet or face
  • unusual hair loss or thinning
  • soreness in the mouth
  • scaling, ulceration, sore formation on the skin
  • pain at the site of injection
  • itching.

Stomach or bowel problems such as:

  • feeling sick
  • vomiting
  • diarrhoea
  • constipation.

Influenza-like symptoms such as:

  • fever
  • headache
  • back-pain
  • cold shivers
  • cough
  • sweating
  • muscle pain
  • unusual tiredness or weakness
  • loss of appetite
  • generally feeling unwell
  • inability to sleep
  • runny or blocked nose, sneezing.

Tell your doctor as soon as possible if you notice any of the following side effects:

  • frequent infections such as fever, severe chills, sore throat or ulcers
  • wheezing or coughing
  • bruising or bleeding more easily than normal
  • tiredness, headaches, being short of breath when exercising.

These may be serious side effects. You may need medical attention.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen:

  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips or tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • rapid laboured breathing; extreme shortness of breath; slightly bluish, greyish or dark purple discolouration of the skin; cold extremities
  • quick shallow breathing followed by shortness of breath and difficulty in breathing
  • bruising or bleeding more easily than normal; yellowing of the skin and/or eyes; passing less urine than is normal
  • confusion
  • visual disturbance
  • seizures, fits or convulsions
  • chest pain, changes in the rhythm or rate of the heart beat.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may occur in some patients. Tell your doctor or health care professional if you notice anything that is making you feel unwell.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some people. Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

The benefits and side effects of DBL™ Gemcitabine for Injection may take some time to occur. Therefore even after you have finished your DBL™ Gemcitabine for Injection treatment you should tell your doctor immediately if you notice any of the side effects listed in this section.

After using DBL™ Gemcitabine for Injection

Storage

DBL™ Gemcitabine for Injection will be stored in the pharmacy or on the ward. The injection should be stored below 25°C

Product description

What it looks like

DBL™ Gemcitabine for Injection is a white to off-white powder.

Ingredients

DBL™ Gemcitabine for Injection contains 200mg, 1g or 2g of gemcitabine hydrochloride as the active ingredient.

Inactive ingredients:

It also contains:

  • mannitol
  • sodium acetate

This medicine does not contain lactose, sucrose, gluten, tartrazine or any azo dyes.

Sponsor

DBL™ Gemcitabine for Injection is supplied by:

Australian Sponsor:

Hospira Australia Pty Ltd
ABN 58 097 064 330
Level 3
500 Collins Street
Melbourne VIC 3000
Australia

New Zealand Sponsor:

Hospira NZ Limited
58 Richard Pearse Drive
Airport Oaks, Mangere 2022
Auckland
New Zealand

DBL™ Gemcitabine for Injection is available in the following strengths:

  • 200 mg/vial AUST R 147440
  • 1 g/vial AUST R 147588
  • 2 g/vial AUST R 147589

This leaflet was updated in December 2015.

BRAND INFORMATION

Brand name

DBL Gemcitabine Powder for Injection

Active ingredient

Gemcitabine

Schedule

S4

 

1 Name of Medicine

Gemcitabine hydrochloride.

6.7 Physicochemical Properties

Gemcitabine hydrochloride is 2'-deoxy-2', 2'-difluorocytidine monohydrochloride (betaisomer). It has a molecular formula of C9H11F2N3O4.HCl and molecular weight of 299.66.

Chemical structure.

The chemical structure of Gemcitabine hydrochloride is shown below.

CAS number.

The CAS registry number is 122111-03-9.

2 Qualitative and Quantitative Composition

200 mg/ vial in single packs.
1 g/ vial in single packs.
2 g/ vial in single packs.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Gemcitabine for Injection is a white to off-white lyophilized powder in a clear glass vial.
DBL Gemcitabine for Injection is a white to off white lyophilised powder to be reconstituted for intravenous use.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Gemcitabine exhibits significant cytotoxic activity against a variety of cultured murine and human tumour cells. It exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis (S-phase) and under certain conditions blocking progression of cells through the GI/S-phase boundary. In vitro the cytotoxic action of gemcitabine is both concentration and time dependent. In animal tumour models, the antitumour activity of gemcitabine is schedule dependent. When administered daily gemcitabine causes death in animals with minimal antitumour activity. However, when an every third or fourth day dosing schedule is used, gemcitabine can be given at nonlethal doses and have excellent antitumour activity against a broad range of mouse tumours.
Gemcitabine (dFdC) is metabolised intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. The cytotoxic action of gemcitabine appears to be due to inhibition of DNA synthesis by two actions of dFdCDP and dFdCTP. First, dFdCDP inhibits ribonucleotide reductase which is uniquely responsible for catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis. Inhibition of this enzyme by dFdCDP causes a reduction in the concentrations of deoxynucleosides in general, and especially in that of dCTP. Second, dFdCTP competes with dCTP for incorporation into DNA. Likewise, a small amount of gemcitabine may also be incorporated into RNA. Thus, the reduction in the intracellular concentration of dCTP potentiates the incorporation of dFdCTP into DNA. DNA polymerase epsilon is essentially unable to remove gemcitabine and repair the growing DNA strands. After gemcitabine is incorporated into DNA, one additional nucleotide is added to the growing DNA strands. After this addition there is essentially a complete inhibition in further DNA synthesis (masked chain termination). After incorporation into DNA, gemcitabine then appears to induce the programmed cellular death process known as apoptosis.

Clinical trials.

Non small cell lung cancer (NSCLC).

Single agent use.

Four phase 2 single agent studies were conducted with the primary endpoint being tumour response and a secondary measure of symptomatic improvement. The studies were conducted using gemcitabine doses from 800-1250 mg/m2 as a single agent. The three major studies conducted resulted in uniform response rates from 19.7-22.5% of evaluable patients and from 17.9-20.5% on an intent to treat based analysis after assessment by external peer review boards. The median response duration was 7.6 to 12.7 months, while the overall median survival (for responders and non responders) was from 8.1 to 9.2 months. The major study conducted had 3 patients (2%) achieve complete response and 30 patients (20%) experience partial response out of 151 patients. The fourth trial which was much smaller, with only a total of 34 patients. The mean effective patient dose in this smaller trial was 741 mg/m2 which was lower than that in the 3 major studies (≥ 960 mg/m2), with a tendency towards dose reduction rather than dose incrementing. A response rate of 1 patient (3.2%) out of 31 evaluable patients was observed. The following shows an integrated summary of adverse events (events that occurred in ≥ 2% of patients without causality assessment) for the 4 pivotal trials (n = 360): dyspnoea = 7.5% (27), anaemia = 6.9% (25), fever = 4.2% (15), nausea = 3.9% (14), vomiting = 3.3% (12), carcinoma of lung = 3.1% (11), pain = 2.5% (9), pneumonia = 2.5% (9), dehydration = 2.2% (8), pleural effusion = 2.2% (8) and discontinuation due to progressive disease = 53.6% (193).

Combination use.

A total of 522 patients were enrolled in a phase 3 randomised trial to receive gemcitabine plus cisplatin (GC) (260) or single agent cisplatin (262) over a 4 week schedule. The median survival was 9.1 months (95% CI 8.3 to 10.6 months) for the GC treated patients, which was significantly superior to cisplatin treated patients [7.6 months (95% CI 6.5 to 8.2 months)] (p = 0.0040). The estimate of median time to disease progression was 5.6 months (95% CI of 4.6 to 6.1 months) for GC treated patients, which was significantly superior to cisplatin treated patients [3.7 months (95% CI 3.3 to 4.2 months)] (p = 0.0013). The overall response rate was 30.4% for GC treated patients and 11.1% for patients treated with single agent cisplatin (p < 0.0001).
A total of 135 patients were enrolled in a phase 3 randomised trial to receive GC (69) or cisplatin plus etoposide (66) over a 3 week schedule. The median survival was 8.7 months (95% CI 7.7 to 10.2 months) for the GC arm and 7.2 months (95% CI 6.1 to 9.8 months) for the patients treated with cisplatin plus etoposide, which was not significantly different. The estimate of median time to disease progression was 6.9 months (95% CI of 5.0 to 8.1 months) for GC treated patients, which was significantly superior to cisplatin plus etoposide treated patients [4.3 months (95% CI 3.5 to 4.7 months)] (p = 0.0147). The overall response rate (intent to treat) was 40.6% for GC treated patients and 21.2% for patients treated with cisplatin plus etoposide (p = 0.0167).

Pancreatic cancer.

Data from two clinical trials evaluated the use of gemcitabine in patients with locally advanced or metastatic pancreatic cancer. The first trial compared gemcitabine to fluorouracil in patients who had received no prior chemotherapy. A second trial studied the use of gemcitabine in pancreatic cancer patients previously treated with Fluorouracil or a Fluorouracil containing regimen.
The primary efficacy parameter in these studies was clinical benefit response. Clinical benefit response is a measure of symptomatic improvement. When these studies were being conducted, a standard validated quality of life instrument was not available for the assessment of patients with pancreatic cancer. Clinical benefit 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 two trials. A patient was considered a clinical responder if either:
(i) the patient showed a > 50% reduction in pain intensity (Memorial Pain Assessment) or analgesic consumption, or a twenty point or greater improvement in performance status (Karnofsky Performance Scale) for a period of at least four consecutive weeks, without showing any sustained worsening in any of the other parameters. Sustained worsening was defined as four consecutive weeks with either an 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 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, prospective, single blinded, two arm, randomised comparison of gemcitabine and Fluorouracil in patients with locally advanced or metastatic pancreatic cancer who had received no prior treatment with chemotherapy. Fluorouracil was administered intravenously at a weekly dose of 600 mg/m2 for 30 minutes. The results for this randomised trial are shown in Table 8. Compared to fluorouracil, patients treated with gemcitabine had statistically significant increase in symptomatic improvement, survival and time to progressive disease (23.8% vs 4.8%).
The second trial was a multicenter, open label study of 63 patients with advanced pancreatic cancer previously treated with Fluorouracil or a Fluorouracil containing regimen. In this study, 27% of the 63 patients who had failed Fluorouracil combinations showed, with gemcitabine a clinical benefit response and a median survival of 3.8 months.

Bladder cancer.

A total of 405 patients were randomised in a phase 3 trial to receive gemcitabine plus cisplatin (GC) or MVAC (methotrexate, vinblastine, adriamycin, cisplatin). Two hundred patients received GC (gemcitabine 1000 mg/m2 on days 1, 8 and 15; cisplatin 70 mg/m2 on day 2) administered intravenously over a 28 day period or MVAC (methotrexate, 30 mg/m2 on days 1, 15 and 22; vinblastine 3 mg/m2 on days 2, 15 and 22; adriamycin 30 mg/m2 on day 2; cisplatin 70 mg/m2 on day 2) administered intravenously over a 28 day period. The median overall survival was 12.8 months (95% CI 12.0 to 15.3 months) for patients treated with GC and 14.8 months (95% CI 13.2 to 17.2 months) for MVAC treated patients, which was not statistically significantly different. The probability of surviving beyond 12 months was estimated as 57% for the GC arm and 62% for the MVAC arm. Median time to progressive disease was 7.4 months (95% CI 6.6 to 8.1 months) for GC treated patients and 7.6 months (95% CI 6.7 to 9.1 months) for MVAC treated patients, which was not statistically significantly different. The independently reviewed, overall response rate was 49.4%, (95% CI 41.7%-57.1%) in the GC arm and 45.7% (95% CI 37.7 to 53.7) in the MVAC arm (p = 0.512). The median duration of response was 9.6 months (95% CI 8.0 to 10.8 months) for GC treated patients and 10.7 months (95% CI 9.4 to 12.6 months) for MVAC treated patients, which was not statistically significantly different.
Phase 2 trials were conducted using single agent gemcitabine, administered at doses of 1200 or 1250 mg/m2 given weekly for 3 out of every 4 weeks. The response rates were 23% (95% CI 9.6-41.2%), 24% (95% CI 11.8-41.1%) and 22% (95% CI 9.8-38.2%). The median survivals were 9.3 months (95% CI 4.9-14.9 months), 12.5 months (95% CI 9.4-14.6 months) and 7.9 months (95% CI 5.8-11.6 months).

Breast cancer.

Data from a pivotal study support the use of gemcitabine in combination with paclitaxel for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant anthracycline based chemotherapy. In this multicentre, open label, randomised phase 3 study, a total of 529 female patients with unresectable, recurrent or metastatic breast cancer were randomised to receive gemcitabine plus paclitaxel (GT) combination therapy (n = 266) or paclitaxel (T) monotherapy (n = 263). In the GT arm gemcitabine (1250 mg/m2) was administered intravenously over 30 to 60 minutes on days 1 and 8 of a 21 day cycle and paclitaxel (175 mg/m2) was administered intravenously over 3 hours before gemcitabine on day 1 of a 21 day cycle. In the T arm paclitaxel (175 mg/m2) was administered intravenously over 3 hours on day 1 of a 21 day cycle. Patients were included in the trial if they had relapsed after receiving either one anthracycline based chemotherapy in the adjuvant/ neoadjuvant setting or a nonanthracycline based regimen in the adjuvant/ neoadjuvant setting if use of an anthracycline was clinically contraindicated.
The study objectives were to compare overall survival time to documented disease progression (TtDDP), progression free survival (PFS), response rates, duration of response and toxicities between patients treated with gemcitabine plus paclitaxel combination therapy and those treated with paclitaxel monotherapy.
The primary endpoint of the planned interim analysis was time to documented progression of disease (TtDPD). Patients who died without evidence of disease progression were excluded from this analysis. Estimates of median TtDPD were 5.4 months (95% CI, 4.6 to 6.1 months) on the GT therapy arm and 3.5 months (95% CI, 2.9 to 4.0 months) on the T arm using the earlier of the dates of disease progression, derived from either the investigator's or the independent reviewers' assessment. The difference between the two treatment arms was statistically significant (p = 0.0013). GT also significantly improved progression free survival by a similar amount. This endpoint accounts for not only patients with documented disease progression but also patients who died without evidence of progression.
Median overall survival analysis showed statistically significant improvement in the gemcitabine plus paclitaxel arm compared with the paclitaxel alone arm, as demonstrated by a longer median survival (18.6 versus 15.8 months, with hazard ration of 0.82 (95% confidence interval [CI], 0.67 to 1.00, log rank p = 0.05).
The overall response rates, according to the investigator assessment were 39.3% (95% CI, 33.5% to 45.2%) on the GT arm and 25.6% (95% CI, 20.3% to 30.9%) on the T arm, which was statistically significant (p = 0.0007). Overall best study response as determined by independent review for a subset of 382 patients (72% of total patients) confirmed that GT treated patients had statistically significant improvement in overall response compared with patients treated with T monotherapy.
There were no significant treatment differences in the patient assessed quality of life measures, Brief Pain Inventory and Rotterdam Symptom Checklist.

Ovarian cancer.

A total of 356 patients with advanced epithelial ovarian cancer who had failed first line platinum containing therapy at least 6 months after treatment discontinuation were randomised to receive gemcitabine plus carboplatin (GCb) (178) or carboplatin (Cb) (178). Patients received either GCb (gemcitabine 1000 mg/m2 on days 1 and 8 and carboplatin administered after gemcitabine on day 1 with a target AUC of 4.0 mg/mL) or Cb (target AUC of 5.0 mg/mL administered on day 1) every 21 days until disease progression or until a maximum of six cycles of treatment had been given.
Patients on the GCb arm had a statistically significant improvement in time to progressive disease (TtPD) compared with those on the Cb arm (hazard ratio, 0.72; 95% CI, 0.57 to 0.90; log rank p value = 0.0038) with a median TtPD of 8.6 months (95% CI, 8.0 to 9.7 months) on the GCb arm versus 5.8 months (95% CI, 5.2 to 7.1 months) on the Cb arm. Patients on the GCb arm had a statistically significant improvement in time to treatment failure (TtTF) compared with those on the Cb arm (hazard ratio 0.74, 95% CI, 0.60 to 0.92; log rank p value = 0.0072). The median TtTF was 7.0 months (95% CI, 5.8 to 8.1 months) on the GCb arm and 4.8 months (95% CI, 4.1 to 5.6 months) on the Cb arm.
Median overall survival was 18.0 months (95% CI, 16.2-20.2) for GCb arm and 17.3 months (95% CI, 15.2-19.3) for the Cb arm (hazard ratio 0.96, 95% CI 0.75-1.23). The trial was not powered to detect an effect on overall survival and treatments received after completion of study therapy were not balanced between arms.

5.2 Pharmacokinetic Properties

The pharmacokinetics of gemcitabine have been examined in 353 patients in seven studies. The 121 women and 232 men ranged in age from 29 to 79 years. Of these patients, approximately 45% had non-small cell lung cancer and 35% were diagnosed with pancreatic cancer. The following pharmacokinetic parameters were obtained for doses ranging from 500 to 2592 mg/m2 that were infused from 0.4 to 1.2 hours.

Absorption.

Peak plasma concentrations (obtained within 5 minutes of the end of the infusion) ranged from 3.2 to 45.5 microgram/mL.

Distribution.

Volume of distribution of the central compartment: 12.4 L/m2 for women and 17.5 L/m2 for men (interindividual variability was 91.9%). Volume of distribution of the peripheral compartment: 47.4 L/m2. The volume of the peripheral compartment was not sensitive to gender. Plasma protein binding was negligible. Systemic clearance ranged from 29.2 L/hr/m2 to 92.2 L/hr/m2 depending on gender and age (interindividual variability was 52.2%). These effects result in interpatient differences in the plasma concentration of gemcitabine and its rate of elimination from the systemic circulation (reflected by differences in half life). Clearance for women is approximately 25% lower than the values for men. Although rapid, clearance for both men and women appears to decrease with age. For the recommended gemcitabine dose of 1000 mg/m2 given as a 30 minute infusion, lower clearance values for women and men should not necessitate a decrease in the gemcitabine dose. The mean renal clearance is 2-7 L/hr/m2 with less than 10% excreted as unchanged drug. Half life ranged from 42 to 94 minutes depending on age and gender. For the recommended dosing schedule, gemcitabine elimination should be virtually complete within 5 to 11 hours of the start of the infusion. Gemcitabine does not accumulate when administered once weekly.

Metabolism.

Gemcitabine is rapidly metabolised by cytidine deaminase in the liver, kidney, blood and other tissues. Intracellular metabolism of gemcitabine produces the gemcitabine mono, di and triphosphates (dFdCMP, dFdCDP and dFdCTP) of which dFdCDP and dFdCTP are considered active. These intracellular metabolites have not been detected in plasma or urine. The primary metabolite 2'-deoxy-2', 2'-difluorouridine (dFdU), is not active and is found in plasma and urine.

dFdCTP kinetics.

This metabolite can be found in peripheral blood mononuclear cells and the information below refers to these cells.
Terminal elimination half-life: 0.7-12 hours.
Intracellular concentrations increase in proportion to gemcitabine doses of 35-350 mg/m2/30 min, which give steady state concentrations of 0.4-5 microgram/mL. At gemcitabine plasma concentrations above 5 microgram/mL, dFdCTP levels do not increase, suggesting that the formation is saturable in these cells. Parent plasma concentrations following a dose of 1,000 mg2/30 min are greater than 5 microgram/mL for approximately 30 minutes after the end of the infusion, and greater than 0.4 microgram/mL for an additional hour.

dFdU kinetics.

Peak plasma concentrations (3-15 minutes after end of 30 minute infusion, 1000 mg/m2): 28-52 microgram/mL.
Trough concentration following once weekly dosing: 0.07-1.12 microgram/mL, with no apparent accumulation.
Triphasic plasma concentration versus time curve, mean half life of terminal phase: 65 hours (range 33-84 hr).
Formation of dFdU from parent compound: 91%-98%.
Mean volume of distribution of central compartment: 18 L/m2 (range 11-22 L/m2).
Mean steady state volume of distribution (Vss): 150 L/m2 (range 96-228 L/m2).
Tissue distribution: extensive.
Mean apparent clearance: 2.5 L/hr/m2 (range 1-4 L/hr/m2).

Excretion.

Urinary excretion: all.

Overall elimination.

Amount recovered in one week: 92%-98%, of which 99% is dFdU, 1% of the dose is excreted in faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Carcinogenesis, mutagenesis, fertility.

Cytogenetic damage has been produced by gemcitabine in an in vivo assay. Gemcitabine induced forward mutation in vitro in a mouse lymphoma (L5178Y) assay. Long term animal studies have not been conducted to evaluate the carcinogenic potential of gemcitabine.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Gemcitabine for Injection is indicated:
For treatment of patients with locally advanced or metastatic non-small cell lung cancer.
For treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas.
For treatment of patients with fluorouracil refractory pancreatic cancer.
Alone or in combination with cisplatin, is indicated for treatment of patients with bladder cancer.
In combination with paclitaxel, for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/ neoadjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contraindicated.
In combination with carboplatin, for the treatment of patients with recurrent epithelial ovarian carcinoma, who have relapsed > six months following platinum based therapy.

4.3 Contraindications

Gemcitabine is contraindicated in those patients with a known hypersensitivity to the medicine.

4.4 Special Warnings and Precautions for Use

Prolongation of the infusion time and the increased dosing frequency have been shown to increase toxicity. In common with other cytotoxic agents, gemcitabine has demonstrated the ability to suppress the bone marrow. Leucopenia, thrombocytopenia and anaemia are expected adverse events. However, myelosuppression is short lived.
Gemcitabine has been reported to cause somnolence. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.
Reports of haemolytic uraemic syndrome (HUS), capillary leak syndrome (CLS), adult respiratory distress syndrome (ARDS), and posterior reversible encephalopathy syndrome (PRES) with potentially severe consequences have been reported in patients receiving gemcitabine as single agent or in combination with other chemotherapeutic agents. These events can be related to vascular endothelial injury possibly induced by gemcitabine. Gemcitabine should be discontinued and supportive measures implemented if any of these develop during therapy. (see Section 4.8 Adverse Effects (Undesirable Effects)).
In addition to ARDS, other severe pulmonary effects such as interstitial pneumonitis and pulmonary oedema have been reported in patients receiving gemcitabine as single agent or in combination with other chemotherapeutic agents. Gemcitabine should be discontinued and supportive measures provided if these effects develop during therapy (see Section 4.8 Adverse Effects (Undesirable Effects)).
Product is for single use in one patient only.
Patients receiving therapy with gemcitabine must be monitored closely. Laboratory facilities should be available to monitor drug tolerance. Resources to protect and maintain a patient compromised by drug toxicity may be required.
Interstitial pneumonitis together with pulmonary infiltrates has been seen in less than 1% of the patients. In such cases, DBL Gemcitabine for Injection treatment must be stopped. Steroids may relieve the symptoms in such situations. Severe rarely fatal pulmonary effects, such as pulmonary oedema, interstitial pneumonitis and acute respiratory distress syndrome (ARDS) have been reported as less common or rare. In such cases, cessation of DBL Gemcitabine for Injection treatment is necessary. Starting supportive treatment at an early stage may improve the situation.

Use in the elderly.

Gemcitabine has been well tolerated in patients over the age of 65. There is no evidence to suggest that dose adjustments are necessary in the elderly, although gemcitabine clearance and half-life are affected by age.

Paediatric use.

Gemcitabine has been studied in limited phase 1 and 2 trials in children in a variety of tumour types. These studies did not provide sufficient data to establish the efficacy and safety of gemcitabine in children.

Effects on laboratory tests.

Therapy should be started cautiously in patients with compromised bone marrow function. As with other oncolytics, the possibility of cumulative bone marrow suppression when using combination or sequential chemotherapy should be considered.
Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts. Suspension or modification of therapy should be considered when drug induced marrow depression is detected. For guidelines regarding dose modifications (see Section 4.2 Dose and Method of Administration). Peripheral blood counts may continue to fall after the medicine is stopped. Laboratory evaluation of renal and hepatic function should be performed periodically. Raised liver transaminases [aspartate aminotransferase (AST) and/ alanine aminotransferase (ALT)] and alkaline phosphatase are seen in approximately 60% of the patients. These increases are usually mild, transient and not progressive, and seldom lead to cessation of treatment (see Section 4.8 Adverse Effects (Undesirable Effects)). Increased bilirubin (WHO toxicity degrees 3 and 4) was observed in 2.6% of the patients. DBL Gemcitabine for Injection should be given with caution to patients with impaired hepatic function.
Administration of gemcitabine in patients with concurrent liver metastases or a pre-existing medical history of hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.
A few cases of renal failure, including haemolytic uraemic syndrome have been reported (see Section 4.8 Adverse Effects (Undesirable Effects)). Gemcitabine should be administered with caution to patients with impaired renal function. DBL Gemcitabine for Injection treatment should be withdrawn if there is any sign of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin levels with simultaneous thrombocytopenia, elevation of serum bilirubin, serum creatinine, urea or LDH. Renal failure may be irreversible despite withdrawal of the DBL Gemcitabine for Injection treatment and may require dialysis.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Radiotherapy.

Concurrent (given together or ≤ 7 days apart). Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of gemcitabine, frequency of gemcitabine administration, dose of radiation, radiotherapy planning technique, the target tissue and target volume. In a single trial where gemcitabine at a dose of 1,000 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, oesophagitis and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4,795 cm3]. The optimum regimen for safe administration of gemcitabine with therapeutic doses of radiation has not yet been determined.
Radiation injury has been reported on targeted tissues (e.g. oesophagitis, colitis and pneumonitis) in association with both concurrent and nonconcurrent use of gemcitabine.
When given in combination with paclitaxel, cisplatin, or carboplatin, the pharmacokinetics of gemcitabine were not altered. Gemcitabine had no effect on paclitaxel pharmacokinetics.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Gemcitabine caused a dose and schedule dependent hypospermatogenesis in male mice (0.9 mg/m2/day or 10.5 mg/m2 weekly administration IP). Although animal studies have shown an effect of gemcitabine on male fertility (1.5 mg/m2/day IP or 30 mg/m2 IP weekly), no effect has been seen on female fertility (up to 4.5 mg/m2/day IV).
(Category D)*
* Category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformation or irreversible damage. These drugs may also have adverse pharmacological effects.
Cytotoxic agents can produce spontaneous abortion, foetal loss and birth defects. DBL Gemcitabine for Injection must not be used during pregnancy. Studies in experimental animals (mice and rabbits at doses up to 4.5 and 1.6 mg/m2/day IV respectively, administered during the period of organogenesis) have shown teratogenicity and embryotoxicity. Perinatal and postnatal studies in mice at doses up to 4.5 mg/m2/day have shown retarded physical development in the offspring. Women of childbearing age receiving gemcitabine should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur.
It is not known whether the medicine is excreted in human milk, however, studies in lactating rats have shown gemcitabine and/or its metabolites in the milk 10 minutes after an IV dose to the dam. The use of gemcitabine should be avoided in nursing women because of the potential hazard to the infant.

4.8 Adverse Effects (Undesirable Effects)

The most commonly reported adverse drug reactions associated with gemcitabine treatment include: nausea with or without vomiting; raised liver transaminases (AST/ALT) and alkaline phosphatase, reported in approximately 60% of patients; proteinuria and haematuria reported in approximately 50% patients; dyspnoea reported in 10-40% of patients (highest incidence in lung cancer patients); and allergic skin rashes, which occur in approximately 25% of patients and are associated with itching in 10% of patients.
The frequency and severity of the adverse reactions are affected by the dose, infusion rate and intervals between doses (see Section 4.4 Special Warnings and Precautions for Use). Dose limiting adverse reactions are reductions in platelet, leucocyte and granulocyte counts (see Section 4.2 Dose and Method of Administration, Dose reduction).
Slightly higher frequencies of serious adverse events were observed in females, reflecting the gender differences in pharmacokinetic parameters (see Section 5.2 Pharmacokinetic Properties). However, the pattern was inconsistent, with some events being more frequently reported for males than females. In analysis of World Health Organisation (WHO) toxicity, no important differences were observed, although slightly higher frequencies of haematologic toxicity were found in females.
Frequencies: very common: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare: ≥ 0.01% and < 0.1%; very rare: < 0.01%.

System organ class.

Blood and lymphatic system disorders.

Very common: leucopenia, thrombocytopenia, anaemia, (neutropenia grade 3 = 19.3%; grade 4 = 6%). Common: febrile neutropenia. Very rare: thrombocytosis.

Immune system disorders.

Very rare: anaphylactoid reaction (see Section 4.3 Contraindications).

Nervous system disorders.

Common: somnolence. Very rare: posterior reversible encephalopathy syndrome (see Section 4.4 Special Warnings and Precautions for Use).

Cardiac disorders.

Rare: myocardial infarct, heart failure, arrhythmia (predominantly supraventricular in nature).

Vascular disorders.

Rare: hypotension. Very rare: clinical signs of peripheral vasculitis and gangrene and capillary leak syndrome (see Section 4.4 Special Warnings and Precautions for Use).

Respiratory, thoracic, and mediastinal disorders.

Very common: dyspnoea. Uncommon: pulmonary oedema, bronchospasm, interstitial pneumonitis (see Section 4.4 Special Warnings and Precautions for Use). Rare: adult respiratory distress syndrome (ARDS) (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal disorders.

Very common: nausea, vomiting. Common: diarrhoea, constipation.

Hepatobiliary disorders.

Very common: elevation of liver transaminases (AST/ALT) and alkaline phosphatase (see Section 4.4 Special Warnings and Precautions for Use). Common: increased bilirubin (see Section 4.4 Special Warnings and Precautions for Use). Rare: elevation of gamma-glutamyl transferase (GGT).

Skin and subcutaneous tissue disorders.

Very common: allergic skin rash, frequently associated with pruritus. Common: alopecia, ulceration of mucous membrane of the mouth, itching. Rare: scaling, vesicle and sore formation, ulceration. Very rare: severe skin reactions, including desquamation and bullous skin eruptions.

Renal and urinary disorders.

Very common: mild proteinuria, haematuria. Rare: renal failure, haemolytic uraemic syndrome (see Section 4.4 Special Warnings and Precautions for Use).

General disorders and administration site conditions.

Very common: oedema/ peripheral oedema, influenza-like symptoms, the most common symptoms are fever, headache, back pain, shivering, muscle pain, asthenia and anorexia. Cough, rhinitis, perspiration, malaise and sleeping difficulties have also been reported. Common: fever, asthenia. Very rare: facial oedema.

Injury, poisoning and procedural complications.

Radiation toxicity and radiation recall (see Section 4.4 Special Warnings and Precautions for Use).

Gemcitabine plus cisplatin.

An increase was seen in the following grade 3 and 4 events (gemcitabine + cisplatin vs MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)) as follows (see Table 5).

Gemcitabine plus paclitaxel.

An increase was seen in the following grade 3 and 4 events (gemcitabine + paclitaxel vs. paclitaxel alone) as follows (see Table 6).

Gemcitabine plus carboplatin.

An increase was seen in the following grade 3 and 4 events (gemcitabine + carboplatin vs. carboplatin alone) as follows (see Table 7).

Toxicity.

In repeat dose studies of up to 6 months duration in mice and dogs, the principal finding was haematopoietic suppression. These effects were related to the cytotoxic properties of the drug and were reversible when treatment was withdrawn. The degree of the effect was schedule and dose dependent.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Nonsmall cell lung cancer.

Single agent use (adults).

The optimum dose schedule for gemcitabine has not been determined. The recommended dose of gemcitabine is 1,000 mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for three weeks, followed by a one week rest period. This four week cycle is then repeated. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Combination use (adults).

Gemcitabine in combination with cisplatin has been investigated using two dosage regimens. One regimen used a three week schedule and the other used a four week schedule.
The three week schedule used gemcitabine 1250 mg/m2, given by 30 minute intravenous infusion, on days 1 and 8 of each 21 day cycle. The three week schedule used cisplatin 75-100 mg/m2 on day 1 of each 21 day cycle, administered before the gemcitabine dose. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient.
The four week schedule used gemcitabine 1,000 mg/m2, given by 30 minute intravenous infusion, on days 1, 8, and 15 of each 28 day cycle. The four week schedule used cisplatin 75-100 mg/m2 on day 1 of each 28 day cycle, administered after the gemcitabine dose. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Pancreatic cancer (adults).

The recommended dose of gemcitabine is 1,000 mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for up to 7 weeks followed by a week of rest. Subsequent cycles should consist of injections once weekly for 3 consecutive weeks out of every 4 weeks. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Bladder cancer.

In patients with bladder cancer who cannot tolerate cisplatin based combinations, gemcitabine monotherapy should be considered a treatment option.

Single agent use (adults).

The recommended dose of gemcitabine is 1250 mg/m2, given by 30 minute intravenous infusion. The dose should be given on days 1, 8 and 15 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Combination use (adults).

The recommended dose for gemcitabine is 1000 mg/m2, given by 30 minute intravenous infusion. The dose should be given on days 1, 8 and 15 of each 28 day cycle in combination with cisplatin. Cisplatin is given at a recommended dose of 70 mg/m2 on day 1 following gemcitabine or day 2 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient. A clinical trial showed more myelosuppression when cisplatin was used in doses of 100 mg/m2.

Breast cancer (adults).

Gemcitabine in combination with paclitaxel is recommended using paclitaxel (175 mg/m2) administered on day 1 over approximately 3 hours as an intravenous infusion, followed by gemcitabine (1250 mg/m2) as a 30 minute intravenous infusion on days 1 and 8 of each 21 day cycle. Dose reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Ovarian cancer (adults).

Gemcitabine in combination with carboplatin is recommended using gemcitabine 1000 mg/m2 administered on days 1 and 8 of each 21 day cycle as a 30 minute intravenous infusion. After gemcitabine, carboplatin should be given on day 1 consistent with target AUC of 4.0 mg/mL/min. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Dose reduction.

Haematological toxicity.

Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts and, if there is evidence of toxicity, the dose of gemcitabine should be reduced or withheld.
Patients receiving gemcitabine should have an absolute granulocyte count of at least 1.5 (x 109/L) and a platelet count of ≥ 100 (x 109/L) prior to initiation of a cycle. Dose modifications of gemcitabine on day 8 and/or day 15 for haematological toxicity should be performed according to the guidelines below (see Tables 1 to 3).

Gemcitabine monotherapy or in combination with cisplatin.


Gemcitabine in combination with paclitaxel.


Gemcitabine in combination with carboplatin.


Other toxicity.

Periodic physical examination and checks of liver and kidney function should be made to detect nonhaematological toxicity. Dosage reduction with each cycle or dose omission within a cycle may be applied based upon the amount of toxicity experienced by the patient. Doses should be withheld until toxicity has resolved in the opinion of the physician.
Gemcitabine is well tolerated during the infusion, with only a few cases of injection site reaction reported. There have been no reports of injection site necrosis. Gemcitabine can be easily administered on an outpatient basis.

Method of administration.

Instructions for use/handling.

The only approved diluent for reconstitution of gemcitabine sterile powder is 0.9% sodium chloride injection without preservatives. No incompatibilities have been identified, however, it is not recommended to mix gemcitabine with other medicines when reconstituted. Due to solubility considerations, the maximum concentration for gemcitabine 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 0.9% sodium chloride injection as directed in Table 4 and shake to dissolve.
These dilutions each yield a gemcitabine concentration of 38 mg/mL, which includes accounting for the displacement volume of the lyophilised powder. Complete withdrawal of the vial contents will provide 200 mg, 1 g or 2 g of gemcitabine, respectively. The appropriate amount of medicine may be administered as prepared or further diluted with 0.9% sodium chloride injection.
Unopened vials should be stored at room temperature. Solutions of reconstituted DBL Gemcitabine for Injection should be stored at room temperature (15°C to 30°C) for up to 24 hours. In order to reduce microbiological hazard, use as soon as practicable after reconstitution/ preparation. Discard unused portion. Solutions of reconstituted gemcitabine should not be refrigerated, as crystallisation may occur.
Parenteral formulations should be inspected visually for particulate matter and discolouration, prior to administration, whenever solution and container permit. Solutions showing evidence of particulate matter and/or discolouration should not be used.
Procedure for proper handling and disposal of anticancer medicines should be considered.

Dosage adjustment.

Hepatic and renal impairment.

Gemcitabine should be used with caution in patients with hepatic insufficiency or with impaired renal function as there is insufficient information from clinical studies to allow clear dose recommendation for this patient population. Dose reduction is recommended in patients with elevated serum bilirubin concentration because such patients are at increased risk of toxicity. In a study of cancer patients with elevated serum bilirubin concentrations (median 50 mmol/L, range 30-100 mmol/L) who were administered gemcitabine monotherapy, 8 out of 10 patients experienced toxicity at a gemcitabine dose of 950 mg/m2 compared with 3 out of 8 at 800 mg/m2. The toxicity was mostly related to the liver.
In the same study, patients with elevated serum creatinine concentration appeared to experience increased sensitivity to gemcitabine. However, the data based on 15 patients was not sufficient to make dosing recommendations.
All combination studies involving gemcitabine and cisplatin have been performed in patients with creatinine clearance > 60 mL/min. There are no safety or pharmacokinetic data available for this combination in patients with creatinine clearance < 60 mL/min.

4.7 Effects on Ability to Drive and Use Machines

Gemcitabine has been reported to cause somnolence. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.

4.9 Overdose

There is no antidote for overdosage of gemcitabine. Single doses as high as 5.7 g/m2 have been administered by IV infusion over 30 minutes every two weeks with clinically acceptable toxicity. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.
In case of overdose, immediately contact the Poison Information Centre for advice (In Australia, call 13 11 26. In New Zealand, call 0800 764 766).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each vial contains gemcitabine hydrochloride and the excipients, mannitol, sodium acetate, hydrochloric acid and sodium hydroxide.

6.2 Incompatibilities

No incompatibilities have been identified, however, it is not recommended to mix gemcitabine with other medicines when reconstituted.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

DBL Gemcitabine for Injection is a white to off-white lyophilized powder in a clear glass vial.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

Procedure for proper handling and disposal of anti-cancer medicines should be considered.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes