DBL™ Pemetrexed (as disodium) powder for infusion

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Pemetrexed disodium 562.43 mg (as 2.5-hydrate, equivalent to pemetrexed 500 mg)
Available from:
Pfizer New Zealand Limited
INN (International Name):
Pemetrexed disodium 562.43 mg (as 2.5-hydrate, equivalent to pemetrexed 500 mg)
Dosage:
500 mg
Pharmaceutical form:
Powder for infusion
Composition:
Active: Pemetrexed disodium 562.43 mg (as 2.5-hydrate, equivalent to pemetrexed 500 mg) Excipient: Hydrochloric acid Mannitol Sodium hydroxide
Units in package:
Vial, glass, clear, Type I, with grey bromobutyl rubber closure, Al seal, flip off top, 50 mL, 1 dose unit
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Chongqing Pharmaceutical Research Institute
Therapeutic indications:
DBL™ Pemetrexed (as disodium) powder for infusion, in combination with cisplatin, is indicated for the treatment of patients with malignant pleural mesothelioma.
Product summary:
Package - Contents - Shelf Life: Vial, glass, clear, Type I, with grey bromobutyl rubber closure, Al seal, flip off top, 50 mL - 1 dose units - 36 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-8972a
Authorization date:
2012-01-06

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NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

DBL™ Pemetrexed (as disodium)

100 mg

500 mg

powder for infusion

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

DBL™ Pemetrexed (as disodium) powder for infusion is supplied as 500 mg and 100 mg

vials. Each 500 mg vial contains pemetrexed disodium equivalent to 500 mg pemetrexed.

Each 100 mg vial contains pemetrexed disodium equivalent to 100 mg pemetrexed

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

DBL™

Pemetrexed (as disodium) powder for infusion is supplied as a sterile lyophilised

powder for intravenous infusion available in single dose vials. The product is a white to either

light yellow or green-yellow lyophilised solid.

4.

CLINICAL PARTICULARS

4.1Therapeutic indications

Malignant Pleural Mesothelioma

DBL™

Pemetrexed

disodium)

powder

infusion,

combination

with

cisplatin,

indicated for the treatment of patients with malignant pleural mesothelioma.

Non-Small Cell lung Cancer

DBL™

Pemetrexed

disodium)

powder

infusion

combination

with

cisplatin

indicated for initial treatment of patients with locally advanced or metastatic non-small cell

lung cancer other than predominantly

squamous cell histology.

DBL™ Pemetrexed (as disodium) powder for infusion as monotherapy is indicated for the

treatment of patients with locally advanced or metastatic non-small cell lung cancer other

than predominantly

squamous cell histology

after prior platinum-based chemotherapy.

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4.2 Dose and method of administration

Dose

DBL™

Pemetrexed

disodium)

powder for infusion should be administered under the

supervision of a qualified physician experienced in the use of antineoplastic agents.

DBL™ Pemetrexed (as disodium) powder for infusion in combination

use with cisplatin:

Adults - The recommended dose of DBL™ Pemetrexed (as disodium) powder for infusion is

500 mg/m

as body surface area (BSA) administered as an intravenous infusion over 10

minutes on the first day of each 21-day cycle.

The recommended dose of cisplatin is 75 mg/m

BSA infused over 2 hours approximately 30

minutes

after

completion

infusion

with

DBL™

Pemetrexed (as disodium) powder for

infusion on the first day of each 21-day cycle. Patients must receive adequate anti-emetic

treatment

appropriate

hydration prior to and/or after receiving cisplatin. See cisplatin

Product Information document for specific dosing advice.

Single agent use:

Adults - The recommended dose of DBL™ Pemetrexed (as disodium) powder for infusion is

500 mg/m

BSA administered as an intravenous infusion over 10 minutes on the first day of

each 21-day cycle.

Premedication Regimen

Skin rash has been reported in patients not pre-treated with a corticosteroid. Pre-treatment

with dexamethasone (or equivalent) reduces the incidence and severity of cutaneous reaction.

In clinical trials, dexamethasone 4 mg was given by mouth twice daily the day before, the day

of, and the day after administration

with pemetrexed.

To reduce toxicity, patients treated with pemetrexed must be instructed to take a low-dose

oral folic acid preparation or a multivitamin containing folic acid on a daily basis. At least 5

daily

doses of folic acid must be taken during the 7-day period preceding the first dose

pemetrexed, and dosing should continue during the full course of therapy and for 21 days

after the last dose of pemetrexed. Patients must also receive one intramuscular injection of

vitamin

during the week preceding the first dose of pemetrexed and every 3 cycles

thereafter. Subsequent vitamin B

injections may be given the same day as pemetrexed. In

clinical trials, the dose of folic acid studied ranged from 350 to 1000µg, and the dose of

vitamin B

received was 1000µg. The most commonly used dose of oral folic acid was

400µg.

Laboratory Monitoring and Dose Reduction Recommendations

Monitoring

- It is recommended that patients receiving DBL™ Pemetrexed (as disodium)

powder for infusion be monitored before each dose with a complete blood count, including a

differential and platelet count. Periodic blood chemistry tests should be collected to evaluate

renal and hepatic function.

Absolute

neutrophil

count

(ANC)

should

1500

cells/mm

platelets

100,000

cells/mm

prior to scheduled administration

of any cycle.

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Dose Reduction Recommendations

- Dose adjustments at the start of a subsequent cycle

should be based on nadir haematologic counts or maximum nonhaematologic toxicity from

preceding

cycle

therapy.

Treatment

delayed

allow

sufficient time for

recovery. Upon recovery, patients should be retreated using the guidelines in Tables 1 - 3

which are suitable for using DBL™ Pemetrexed (as disodium) powder for infusion as a

single agent or in combination

with cisplatin.

Table 1. Dose Modification for DBL™ Pemetrexed (as disodium) powder for infusion

(single agent or in combination) and Cisplatin Haematologic Toxicities

Nadir

<500/mm

nadir

platelets ≥50,000/mm

75% of previous dose (DBL™ Pemetrexed (as

disodium)

powder for infusion and cisplatin).

Nadir

platelets

≤50,000/mm

without

bleeding regardless of nadir ANC.

75% of previous dose (DBL™ Pemetrexed (as

disodium)

powder for infusion and cisplatin).

Nadir

platelets

<50,000/mm

with

bleeding

regardless of nadir ANC.

50% of previous dose (DBL™ Pemetrexed (as

disodium)

powder for infusion and cisplatin)

These criteria meet the National Cancer Institute Common Toxicity Criteria version 2.0 (NCI 1998) definition

of ≥ CTC Grade 2 bleeding

If patients develop nonhaematologic toxicities (excluding neurotoxicity) ≥ Grade 3, treatment

should be withheld until resolution to less than or equal to the patient’s pre-therapy value.

Treatment should be resumed according to the guidelines in Table 2.

Table 2: Dose Modification for DBL™ Pemetrexed (as disodium) powder for infusion

(single agent or in combination) and Cisplatin Nonhaematologic Toxicities

a,b

Dose

DBL™

Pemetrexed

disodium)

powder

infusion (mg/m

Dose

cisplatin

(mg/m

Grade

toxicities

except

mucositis

75% of previous dose

75% of previous dose

diarrhoea

requiring

hospitalisation

(irrespective of grade) or grade 3 or 4

diarrhoea

75% of previous dose

75% of previous dose

Grade 3 or 4 mucositis

50% of previous dose

100% of previous dose

NCI CTC ;

Excluding neurotoxicity.

In the event of neurotoxicity, the recommended dose adjustment for pemetrexed and cisplatin

is documented in Table3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is

observed.

Table 3. Dose Modification for DBL™ Pemetrexed (as disodium) powder for infusion

(single agent or in combination) and Cisplatin Neurotoxicity

Grade

Dose for DBL™ Pemetrexed (as disodium) powder for

infusion (mg/m

Dose

cisplatin

(mg/m

100% of previous dose

100%

previous

dose

100% of previous dose

50% of previous dose

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DBL™ Pemetrexed (as disodium) powder for infusion therapy should be discontinued if a

patient experiences any haematologic or nonhaematologic Grade 3 or 4 toxicity after 2 dose

reductions or immediately

if Grade 3 or 4 neurotoxicity

is observed.

Elderly Patients

— In clinical trials, there has been no indication that patients 65 years of

age or older are at increased risk of adverse events compared with patients younger than 65.

No dose reductions other than those recommended for all patients are necessary.

Renally Impaired Patients

— In clinical studies, patients with creatinine clearance of at

least 45 mL/min required no dose adjustments other than those recommended for all patients.

Insufficient

numbers

patients

with

creatinine

clearance

below

mL/min

have

been

treated

make

dosage

recommendations

this

group

patients.

Therefore, patients

should not receive DBL™ Pemetrexed (as disodium) powder for infusion whose creatinine

clearance is <45 mL/min [using the standard Cockcroft and Gault formula or GFR measured

by Tc99m-DPTA serum clearance method].

Method of Administration

Preparation and administration instructions: Use aseptic technique.

Reconstitution

further

dilution

prior

intravenous

infusion

only

recommended

with

0.9%

sodium chloride injection. DBL™ Pemetrexed (as disodium) powder for infusion is

physically

incompatible

with

diluents

containing

calcium,

including

Lactated

Ringer’s

Injection

Ringer’s

Injection.

Co-administration

DBL™

Pemetrexed

disodium)

powder for infusion with other drugs and diluents has not been studied, and therefore is not

recommended.

Use appropriate aseptic technique during the reconstitution and further dilution of DBL™

Pemetrexed (as disodium) powder for infusion for intravenous infusion administration.

Calculate the dose and the number of DBL™ Pemetrexed (as disodium) powder for

infusion vials needed. A 500 mg vial contains 500 mg of pemetrexed. A 100 mg vial

contains 100 mg of pemetrexed. The vial contains an excess of pemetrexed to facilitate

delivery of label amount.

Prior to administration, reconstitute 500 mg vials with 20 mL of 0.9% sodium chloride

injection to give a solution containing 25 mg/mL pemetrexed. Reconstitute 100 mg vials

with 4.2 mL of 0.9% sodium chloride injection to give a solution containing 25 mg/mL

pemetrexed.

Gently swirl each vial until the powder is completely dissolved. The resulting solution is

clear and ranges in colour from colourless to yellow or green-yellow without adversely

affecting product quality. The pH of the reconstituted DBL™ Pemetrexed (as disodium)

powder

infusion

solution

between

7.8.

FURTHER

DILUTION

REQUIRED.

The appropriate volume of reconstituted DBL™ Pemetrexed (as disodium) powder for

infusion solution should be further diluted to 100 mL with 0.9% sodium chloride injection

and administered as an intravenous infusion over 10 minutes.

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Parenteral

drug

products

should

inspected

visually

particulate

matter

discolouration

prior to administration.

Chemical and physical stability of reconstituted and infusion solutions of DBL™ Pemetrexed

(as disodium) powder for infusion was demonstrated for up to 24 hours after reconstitution of

original

vial

when

stored

below

However,

because

DBL™

Pemetrexed

disodium)

powder

infusion

recommended

diluent

contain

antimicrobial

preservatives, to reduce antimicrobial hazard, reconstituted and infusion solutions should be

used immediately. Discard any unused portion. Product is for single use in one patient on one

occasion only.

4.3 Contraindications

Pemetrexed is contraindicated in women of childbearing age unless adequate contraception is

used. DBL™ Pemetrexed (as disodium) powder for infusion is contraindicated in patients

who have a history of severe hypersensitivity reaction to pemetrexed or to any excipients in

this product.

4.4 Special warnings and precautions for use

DBL™ Pemetrexed (as disodium) powder for infusion can suppress bone marrow function as

manifested by anaemia, neutropenia, thrombocytopenia, or pancytopenia. (see

section 4.8).

Myelosuppression

usually

dose-limiting

toxicity.

Patients

should

monitored

myelosuppression during therapy and DBL™ Pemetrexed (as disodium) powder for infusion

should

given

patients until absolute neutrophil count

(ANC)

returns

1500

cells/mm

and platelet count returns to ≥ 100,000 cells/mm

. Dose reductions for subsequent

cycles are based on nadir ANC, platelet count, and maximum nonhaematologic toxicity seen

in the previous cycle (see

section 4.2).

Patients

treated

with

DBL™

Pemetrexed

disodium)

powder

infusion

must

instructed to take folic acid and vitamin B

with DBL™ Pemetrexed (as disodium) powder

for infusion as a prophylactic measure to reduce treatment-related toxicity (see

section 4.2).

In the Phase 3 mesothelioma EMPHACIS trial, less overall toxicity and reductions in Grade

haematologic

nonhaematologic

toxicities

such

neutropenia,

febrile neutropenia,

and infection with Grade 3/4 neutropenia were reported when pre-treated with folic acid and

vitamin B

was administered.

Serious renal events, including acute renal failure, have been reported with pemetrexed alone

or in association with other chemotherapeutic agents. Many of the patients in whom these

occurred

underlying

risk

factors

development

renal

events

including

dehydration or pre-existing hypertension or diabetes.

Due to the gastrointestinal toxicity of pemetrexed given in combination with cisplatin, severe

dehydration

been

observed.

Therefore,

patients

should

receive

adequate

antiemetic

treatment and appropriate hydration prior to and/or after receiving treatment.

Serious

cardiovascular

events,

including

myocardial

infarction

cerebrovascular

events

have been uncommonly reported during clinical studies with pemetrexed, usually when given

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in combination with another cytotoxic agent. Most of the patients in whom these events have

been observed had pre-existing cardiovascular risk factors.

Immunodepressed status is common in cancer patients. As a result, concomitant use of live

attenuated vaccines is not recommended.

Cases of radiation pneumonitis have been reported in patients treated with radiation either

prior, during or subsequent to their pemetrexed therapy. Particular attention should be paid to

these

patients

caution exercised with use of other radio-sensitising agents. Cases of

radiation recall have been reported in patients who received radiotherapy weeks or years

previously.

Renally

Impaired

Patients

Pemetrexed

primarily

eliminated

unchanged

renal

excretion. Insufficient numbers of patients have been studied with creatinine clearance below

45 mL/min. Therefore, DBL™ Pemetrexed (as disodium) powder for infusion should not be

administered to patients whose creatinine clearance is <45 mL/min (see

section 4.2).

Hepatically Impaired Patients

— Pemetrexed is not extensively metabolised by the liver.

However, patients with hepatic impairment such as bilirubin >1.5 times the upper limit of

normal (ULN) or transaminase >3 times the ULN (hepatic metastases absent) or >5 time the

ULN (hepatic metastases present) have not been specifically studied.

DBL™

Pemetrexed

disodium)

powder for infusion should be administered under the

supervision

qualified

physician

experienced

antineoplastic

agents.

Appropriate

management

complications

possible only when adequate diagnostic and

treatment

facilities

readily

available. Treatment-related adverse events of pemetrexed

seen in clinical trials have been reversible. Skin rash has been reported in patients not pre-

treated

with

corticosteroid

clinical

trials.

Pre-treatment

with

dexamethasone

equivalent) reduces the incidence and severity of cutaneous reaction (see

section 4.2).

effect

third

space

fluid,

such

pleural

effusion

ascites,

on pemetrexed is

unknown.

patients

with

clinically

significant

third

space

fluid,

consideration

should

given to draining the effusion prior to DBL™ Pemetrexed (as disodium) powder for infusion

administration.

Elderly Use

In clinical studies, there has been no indication that patients 65 years of age or

older are at increased risk of adverse events compared to patients younger than 65 years old.

No dose reductions other than those recommended for all patients are necessary.

Paediatric population

DBL™ Pemetrexed (as disodium) powder for infusion is not recommended for use in patients

under 18 years of age, as safety and efficacy have not been established in this group of

patients

4.5 Interaction with other medicines and other forms of interaction

Pemetrexed is primarily eliminated unchanged renally as a result of glomerular filtration and

tubular secretion.

In vitro

studies indicate that pemetrexed is actively secreted by the organic

anion transporter 3 (OAT3) in the kidney. In Vitro work also indicates that pemetrexed has

affinity

OAT4

role

of OAT4 in the renal elimination of molecules in not fully

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understood.

Concomitant

administration

nephrotoxic

drugs

and/or

substances

that

tubularly secreted could result in delayed clearance of pemetrexed.

Results from

in vitro

studies with human liver microsomes suggest that pemetrexed would

cause

clinically

significant

interactions

with

drugs

metabolised by CYP3A, CYP2D6,

CYP2C9, and CYP1A2.

The pharmacokinetics of pemetrexed are not influenced by oral folic acid and intramuscular

vitamin

supplementation

concurrently

administered

cisplatin.

Total

platinum

clearance is not affected by pemetrexed administration.

Although NSAIDs in moderate doses can be administered with pemetrexed in patients with

normal renal function (creatinine clearance ≥ 80 mL/min), renal clearance was reduced by

16% when ibuprofen was concurrently administered with pemetrexed in patients with normal

renal

function.

Caution

should

used

when

administering

NSAIDs

concurrently

with

pemetrexed to patients with mild to moderate renal insufficiency (creatinine clearance of 45-

79 mL/min). It is recommended that patients with mild to moderate renal insufficiency should

avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day

of, and 2 days following

administration of pemetrexed.

In the absence of data regarding potential interaction between pemetrexed and NSAIDs with

longer half-lives in patients with mild to moderate renal insufficiency, all patients eligible for

Pemetrexed therapy taking these NSAIDs should interrupt dosing for at least 5 days before,

the day of, and 2 days following pemetrexed administration. If concomitant administration of

NSAIDs

necessary,

patients

should

monitored

closely

toxicity,

especially

myelosuppression

and gastrointestinal

toxicity.

4.6 Fertility, pregnancy and lactation

Fe rtility

Administration

pemetrexed

male

mice

intraperitoneal

doses

mg/m

/day

resulted

reproductive

toxicity

characterised

reduced

fertility,

hypospermia,

testicular atrophy.

Pregnancy

Pregnancy Category D

DBL™ Pemetrexed (as disodium) powder for infusion should be avoided in

pregnant women because of the potential hazard to the foetus. Pemetrexed was teratogenic

(causing cleft palate) in mice at intravenous doses of 15 mg/m

/day. Other embryofetal toxic

effects

(embryofetal

deaths, reduced fetal weights and incomplete ossification) were also

observed. Embryofetal toxicity was observed at the lowest dose tested (0.6 mg/m

/day).

Lactation

It is not known whether pemetrexed is excreted in human milk. Therefore, breast-feeding

should be discontinued during therapy with DBL™ Pemetrexed (as disodium) powder for

infusion.

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4.7 Effects on ability to drive and use machinery

No studies on the effects on the ability to drive and use machines have been performed.

However, it has been reported that pemetrexed may cause fatigue. Therefore patients should

be cautioned against driving or operating machinery if this event occurs.

4.8 Undesirable effects

Single agent pemetrexed (NSCLC):

Table 4 provides the frequency and severity of undesirable effects that have been reported in

>5% of 265 patients randomly assigned to receive single agent pemetrexed with folic acid

and vitamin B

supplementation and 276 patients randomly assigned to receive single agent

docetaxel.

patients

were

diagnosed

with

locally

advanced or metastatic NSCLC and

received prior chemotherapy.

Table 4

System

Organ

Class

Frequency

Event*

pemetrexed

(N=265)

docetaxel (N=276)

All

Grades

Toxicity

(%)

Grade

3

4

Toxicity

(%)

All

Grades

Toxicity

(%)

Grade

3

4

Toxicity

(%)

Blood

Lymphatic

System

Disorders

Very

Common

Haemoglobin

19.2

22.1

Leukocytes

12.1

34.1

27.2

Neutrophils/

Granulocytes

10.9

45.3

40.2

Common

Platelets

Gastrointestinal

Disorders

Very

Common

Nausea

30.9

16.7

Anorexia

21.9

23.9

Vomiting

16.2

12.0

Stomatitis/

Pharyngitis

14.7

17.4

Diarrhoea

12.8

24.3

Common

Constipation

General

Disorders

Very

Common

Fatigue

34.0

35.9

Common

Fever

Hepatobiliary

Disorders

Common

ALT (SGPT)

AST (SGOT)

Skin

Subcutaneous

Tissue

Disorders

Very

Common

Rash/

Desquamation

14.0

Common

Pruritis

Alopecia

0.4**

37.7

2.2**

* Refer to National Cancer Institute Common Toxicity (NCI CTC) Criteria for lab values for each Grade of

toxicity (version 2.0).

** According to NCI CTC Criteria (version 2.0), alopecia should only be reported as Grade 1 or 2.

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Very common: ≥ 10%; Common: > 5% and <10% (for the purpose of this table a cut off of

5% was used for inclusion of all events where the reporter considered a possible relationship

to pemetrexed)

Clinically

relevant

toxicity

that

reported

(common)

patients

that

were

randomly

assigned

pemetrexed

include:

sensory

neuropathy,

motor

neuropathy,

abdominal

pain,

increased

creatinine,

febrile

neutropenia,

infection

without

neutropenia, allergic reaction/hypersensitivity

and erythema multiforme.

Clinically relevant CTC toxicity that was reported in <1% (uncommon) of the patients that

were randomly assigned to pemetrexed include supraventricular arrhythmias.

Clinically relevant Grade 3 and Grade 4 laboratory toxicities were similar between integrated

Phase 2 results from three single agent pemetrexed studies (n=164) and the Phase 3 single

agent pemetrexed study described above, with the exception of neutropenia (12.8% versus

5.3%, respectively) and alanine transaminase elevation (15.2% versus 1.9%, respectively).

These differences were likely due to differences in the patient population, since the phase 2

studies included chemonaive and heavily pre-treated breast cancer patients with pre-existing

liver metastases and/or abnormal baseline liver function tests.

Combination with cisplatin (MPM):

Table 5 provides the frequency and severity of undesirable effects that have been reported in

>5% of 168 patients with mesothelioma who were randomly assigned to receive cisplatin and

pemetrexed and 163 patients with mesothelioma randomly assigned to receive single agent

cisplatin. In both treatment arms, these chemonaive patients were fully supplemented with

folic acid and vitamin B

Table 5

System Organ

Class

Frequency

Event*

pemetrexed/cisplatin

(N = 168)

cisplatin

(N = 163)

All

Grades

Toxicity

(%)

Grade

3 – 4

Toxicity

(%)

All

Grades

Toxicity

(%)

Grade

3 – 4

Toxicity

(%)

Blood

Lymphatic

System

Disorders

Very

Common

Neutrophils

56.0

23.2

13.5

Leukocytes

53.0

14.9

16.6

Haemoglobin

26.2

10.4

Platelets

23.2

Eye Disorders

Common

Conjunctivitis

Gastrointestinal

Disorders

Very

Common

Nausea

82.1

11.9

76.7

Vomiting

56.5

10.7

49.7

Stomatitis/

Pharyngitis

23.2

Anorexia

20.2

14.1

Diarrhoea

16.7

Constipation

11.9

Common

Dyspepsia

General

Disorders

Very

Common

Fatigue

47.6

10.1

42.3

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Metabolism

Nutrition

Disorders

Common

Dehydration

Nervous

System

Disorders

Very

Common

Neuropathy-

sensory

10.1

Common

Taste

disturbance

0.0***

0.0***

Renal

Disorders

Very

Common

Creatinine

Clearance

Decreased**

10.7

Genitourinary

Other

16.7

18.4

Skin

Subcutaneous

Tissue

Disorders

Very

Common

Rash

16.1

Alopecia

11.3

0.0***

0.0***

* Refer to NCI CTC (version 2.0) for each Grade of toxicity except the term “creatinine clearance decreased”**

which is derived from the CTC term “renal/genitourinary-other”.

*** According to NCI CTC Criteria (version 2.0), alopecia and taste disturbance should only be reported as

Grade 1 or 2.

Very common: > 10%; Common: > 5% and <10% (for the purpose of this table a cut off of

5% was used for inclusion of all events where the reporter considered a possible relationship

to pemetrexed and cisplatin).

Clinically relevant toxicity that was reported in ≥ 1% and ≤ 5% (common) of the patients that

were randomly assigned to receive cisplatin and pemetrexed include: increased AST (SGOT),

ALT (SGPT), and GGT, infection, febrile neutropenia, renal failure, chest pain, pyrexia and

urticaria.

Clinically relevant toxicity that was reported in <1% (uncommon) of the patients that were

randomly

assigned

receive

cisplatin

pemetrexed

include

arrhythmia

motor

neuropathy.

Combination with cisplatin (NSCLC)

Table 6 provides the frequency and severity of undesirable effects considered possibly related

study

drug

that

have

been reported in >5% of 839 patients with NSCLC who were

randomised to study and received cisplatin and pemetrexed and 830 patients with NSCLC

who were randomised to study and received cisplatin and gemcitabine. All patients received

study therapy as initial treatment for locally advanced or metastatic NSCLC and patients in

both treatment groups were fully supplemented with folic acid and vitamin B

Table 6

System Organ

Class

Frequenc

y

Event*

pe me tre xe d/cisplati

n

(N = 839)

ge mcitabine /Cisplati

n

(N = 830)

All

Grades

Toxicity

(%)

Grade

3 – 4

Toxicity

(%)

All

Grades

Toxicity

(%)

Grade

3 – 4

Toxicity

(%)

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