Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
PROFESSIONAL INFORMATION FOR PEMINJO  
SCHEDULING STATUS  
S4  
1 NAME OF THE MEDICINE  
PEMINJO 100 INJ powder for solution for infusion  
PEMINJO 500 INJ powder for solution for infusion  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each vial of PEMINJO 100 INJ contains pemetrexed disodium equivalent to 100 mg pemetrexed  
after reconstitution each vial contains 25 mg/mL pemetrexed.  
Each vial of PEMINJO 500 INJ contains pemetrexed disodium equivalent to 500 mg pemetrexed  
after reconstitution each vial contains 25 mg/mL pemetrexed.  
Excipients  
Contains sugar: mannitol.  
PEMINJO 100 INJ contains 106 mg mannitol per vial.  
PEMINJO 500 INJ contains 500 mg mannitol per vial.  
For full list of excipients, see section 6.1  
3 PHARMACEUTICAL FORM  
PEMINJO is a white to either light yellow or green- yellow lyophilised cake.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
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Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
PEMINJO is indicated for the treatment of patients with malignant pleural mesothelioma in combination  
with cisplatin.  
PEMINJO is indicated in combination with cisplatin therapy for the initial treatment of patients with  
locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell  
histology. PEMINJO is indicated as monotherapy for the treatment of patients with locally advanced or  
metastatic adenocarcinoma of the lung after prior chemotherapy.  
PEMINJO is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic  
adenocarcinoma of the lung in patients whose disease has not progressed immediately following  
standard chemotherapy.  
4.2 Posology and method of administration  
PEMINJO should only be administered under the supervision of a medical practitioner qualified in the  
use of anti-cancer chemotherapy.  
Posology  
Malignant pleural mesothelioma:  
Combination use with cisplatin:  
Adults: In patients treated for malignant pleural mesothelioma, the recommended dose of PEMINJO is  
500 mg/m2 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/m2 infused over 2 hours approximately 30 minutes  
after completion of PEMINJO infusion on the first day of each 21-day cycle. Patients should receive  
hydration consistent with local practice prior to and/or after receiving cisplatin.  
Adenocarcinoma of the lung:  
Single medicine use:  
Adults: In patients treated for adenocarcinoma of the lung, the recommended dose of PEMINJO is 500  
mg/m2 administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.  
Combination use with cisplatin:  
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Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
Adults: In patients treated for non-small cell lung cancer, the recommended dose of PEMINJO is 500  
mg/m2 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/m2 infused over 2 hours approximately 30 minutes after  
completion of the pemetrexed infusion on the first day of each 21-day cycle. Patients should receive  
appropriate hydration prior to and/or after receiving cisplatin.  
Premedication regimen:  
To reduce the incidence and severity of skin reactions, a corticosteroid should be given the day prior  
to, on the day of, and the day after PEMINJO administration. The corticosteroid should be equivalent  
to 4 mg of dexamethasone administered orally twice a day (see section 4.4).  
To reduce toxicity, patients treated with PEMINJO should also receive vitamin supplementation (see  
section 4.4). Patients must take oral folic acid or multivitamin containing folic acid (350 to 1000 μg) on  
a daily basis. At least 5 daily doses of folic acid must be taken during the 7 days preceding the first dose  
of PEMINJO, and dosing should continue during the full course of therapy and for 21 days after the last  
dose of PEMINJO. Patients must also receive an intramuscular injection of vitamin B12 (1000 μg) in the  
week preceding the first dose of PEMINJO and every 3 cycles thereafter.  
Monitoring:  
Patients receiving PEMINJO should be monitored before each dose with a full 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 be cells ≥1500 cells/mm3 and platelets  
should be≥100 000 cells/mm3 prior to the start of each cycle.  
Dose adjustments:  
Dose adjustments at the start of a subsequent cycle should be based on nadir haematologic counts or  
maximum non haematologic toxicity from the preceding cycle of therapy. Treatment may be delayed to  
allow sufficient time for recovery. Upon recovery, patients may be retreated using the guidelines in  
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Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
Tables 1, 2 and 3, which are applicable for PEMINJO used as a single medicine or in combination with  
cisplatin.  
TABLE 1: DOSE MODIFICATION TABLE FOR PEMINJO (AS A SINGLE MEDICINE OR IN  
COMBINATION) AND CISPLATIN: HAEMATOLOGIC TOXICITIES  
Nadir ANC <500/mm3 and nadir platelets 75 % of previous dose PEMINJO and  
≥50 000/mm3  
Nadir platelets ≤50 000/mm3 without 50 % of previous dose PEMINJO and  
bleeding regardless of nadir ANC cisplatin  
Nadir platelets ≤50 000 mm3 with bleeding* 50 % of previous dose PEMINJO and  
regardless of nadir ANC cisplatin  
cisplatin  
*These criteria meet the National Cancer Institute, Common Toxicity Criteria version 2.0 (NCL 1998)  
definition of ≥ CTC Grade 2 bleeding)  
If patients develop non-haematologic 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 TABLE FOR PEMINJO (AS SINGLE MEDICINE OR IN  
COMBINATION) AND CISPLATIN: NON-HAEMATOLOGICTOXICITIES a,b  
Dose  
of  
Dose  
of  
cisplatin  
PEMINJO  
(mg/m2)  
(mg/m2)  
Any Grade 3c or 4 toxicities except 75 % of previous 75 % of previous dose  
mucositis dose  
Any diarrhoea requiring hospitalisation 75 % of previous 75 % of previous dose  
(irrespective of grade) or Grade 3 or 4 dose  
diarrhoea  
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Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
Grade 3 or 4 mucositis  
50 % of previous 100 % of previous dose  
dose  
a National Cancer Institute Common Toxicity Criteria (CTC)  
b Excluding neurotoxicity  
cExcept Grade 3 transaminase elevation  
In the event of neurotoxicity, the recommended dose adjustment for PEMINJO and cisplatin is  
documented in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is observed.  
TABLE 3 – DOSE MODIFICATION TABLE FOR PEMINJO (AS  
A
SINGLE MEDICINE OR IN COMBINATION) AND  
CISPLATIN: NEUROTOXICITY  
CTC* Grade  
Dose  
(mg/m2)  
of  
PEMINJO Dose of Cisplatin (mg/m2)  
0 – 1  
100 % of previous dose  
100 % of previous dose  
100 % of previous dose  
50 % of previous dose  
2
*Common Toxicity Criteria (CTC)  
Treatment with PEMINJO should be discontinued if a patient experiences any haematologic or non-  
haematologic Grade 3 or 4 toxicity after two dose reductions or immediately if Grade 3 or 4 neurotoxicity  
is observed.  
Special populations  
Elderly population:  
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.  
Renal impairment:  
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Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
PEMINJO is primarily eliminated unchanged by renal excretion. Patients with creatinine clearance of  
≥45 ml/min required no dosage adjustments other than those recommended to all  
patients. There are insufficient data on the use of PEMINJO in patients with creatinine clearance below  
45 ml/min; therefore the use of PEMINJO is not recommended (see section 4.4).  
Hepatic impairment:  
No relationships between AST (SGOT), ALT (SGPT), or total bilirubin and pemetrexed  
pharmacokinetics were identified. However, patients with hepatic impairment such as bilirubin >1,5  
times the upper limit of normal and/or transaminase >3,0 times the upper limit of normal (hepatic  
metastases absent) or >5,0 times the upper limit of normal (hepatic metastases present) have not been  
specifically studied.  
Paediatric population:  
PEMINJO 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.  
Method of administration  
Intravenous Infusion.  
For instructions on reconstitution and dilution of PEMINJO before administration,  
see section 6.6.  
4.3 Contraindications  
•
PEMINJO is contraindicated in patients with known hypersensitivity to pemetrexed or to any of  
the excipients listed in Section 6.1  
•
•
PEMINJO is contraindicated in breast-feeding patients (see section 4.6).  
Concomitant use of PEMINJO and yellow fever vaccine is contraindicated.  
4.4 Special warnings precautions for use  
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PEMINJO can suppress bone marrow function as manifested by neutropenia, thrombocytopenia,  
anaemia or pancytopenia (see section 4.8).  
Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for  
myelosuppression during therapy and PEMINJO should not be given to patients until absolute  
neutrophil count (ANC) returns to ≥1500 cells/mm3 and platelet count returns to ≥100 000 cells/mm3.  
Dose reductions for subsequent cycles are based on nadir ANC, platelet count and maximum non-  
haematologic toxicity seen from the previous cycle (see section 4.2). Less toxicity and reduction in  
Grade 3/4 haematological and non- haematological toxicities, such as neutropenia, febrile neutropenia,  
and infection with Grade 3/4 neutropenia, were reported when pre-treatment with folic acid and vitamin  
B12 was administered. Therefore, all patients treated with PEMINJO must be instructed to take folic  
acid and vitamin B12 as a prophylactic measure to reduce treatment-related toxicity (see section 4.2).  
Skin reactions have been reported in patients not pre-treated with a corticosteroid. Pre-treatment with  
dexamethasone (or equivalent) can reduce the incidence and severity of skin reactions (see Section  
4.2).  
An insufficient number of patients with creatinine clearance of below 45 ml/min has been studied.  
Therefore, the use of PEMINJO in patients with creatinine clearance of < 45 ml/min is not recommended  
(see section 4.2).  
Patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 ml/min) should  
avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and acetylsalicylic acid  
(>1,3 g daily) with short elimination half-lives for at least 2 days prior to, on the day of, and at least 2  
days after administration of PEMINJO (see section 4.5).  
All patients eligible for PEMINJO therapy should avoid taking NSAIDs with long elimination half-lives at  
least 5 days prior to, on the day of and at least 2 days after PEMINJO administration (see section 4.5).  
Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in  
association with other chemotherapeutic medicines. Many of the patients in whom these occurred had  
underlying risk factors for the development of renal events, including dehydration or pre-existing  
hypertension or diabetes. Nephrogenic diabetes insipidus and renal tubular necrosis were also reported  
in post-marketing setting with pemetrexed alone or with other chemotherapeutic medicines (see section  
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Product proprietary name: PEMINJO 100/500 INJ  
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4.8). Most of these events resolved after pemetrexed withdrawal. Patients should be monitored for acute  
tubular necrosis and decreased renal function and signs and symptoms of nephrogenic diabetes  
insipidus (e.g. hypernatraemia).  
The effect of third-space fluid, such as pleural effusion or ascites, on pemetrexed is not fully defined,  
therefore, drainage of third-space fluid collection prior to PEMINJO treatment should be considered but  
may not be necessary.  
Due to the gastrointestinal toxicity of PEMINJO given in combination with cisplatin, severe dehydration  
has been observed. Therefore, patients should receive adequate anti-emetic treatment  
and appropriate hydration prior to and/or after receiving treatment.  
Serious cardiovascular events, including myocardial infarction and cerebrovascular events, have been  
uncommonly reported with pemetrexed, usually when given in combination with another cytotoxic  
medicine (see section 4.8). 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 (see section 4.3 and 4.5).  
PEMINJO can have genetically damaging effects. Sexually mature males are advised not to father a  
child during the treatment and up to 6 months thereafter. Contraceptive measures or abstinence are  
recommended. Due to the possibility of PEMINJO treatment causing irreversible infertility, men are  
advised to seek counselling on sperm storage before starting treatment (see section 4.6).  
Women of childbearing potential must use effective contraception during treatment with PEMINJO and  
for 6 months following completion of treatment (see section 4.6).  
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, and  
caution exercised with use of other radiosensitising medicines. Cases of radiation recall have been  
reported in patients who received radiotherapy weeks or years previously.  
4.5 Interaction with other medicines and other forms of interaction  
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Pemetrexed is primarily eliminated unchanged renally as a result of glomerular filtration and tubular  
secretion. Concomitant administration of nephrotoxic medicines (e.g. aminoglycosides, loop diuretics,  
platinum compounds, ciclosporin) could potentially result in delayed clearance of pemetrexed. This  
combination should be used with caution. If necessary, creatinine clearance should be closely  
monitored.  
Concomitant administration of medicines that are also tubularly secreted (e.g. probenecid, penicillin)  
could potentially result in delayed clearance of pemetrexed. Caution should be used when these  
medicines are combined with PEMINJO. If necessary, creatinine clearance should be closely  
monitored.  
In patients with normal renal function (creatinine clearance ≥ 80 ml/min), high doses of nonsteroidal  
anti-inflammatory drugs (NSAIDs, such as ibuprofen > 1600 mg/day) and acetylsalicylic acid at higher  
dose (≥1.3 g daily) may decrease pemetrexed elimination and consequently, increase the occurrence  
of PEMINJO advents events. Therefore, caution should be exercised when administering higher doses  
of NSAIDs or acetylsalicylic acid, concurrently with PEMINJO to patients with normal renal function  
(creatinine clearance ≥ 80 ml/min).  
In patients with mild to moderate renal insufficiency (creatinine clearance 45 – 79 ml/min), the  
concomitant administration of PEMINJO with NSAIDs (e.g. ibuprofen) or acetylsalicylic  
acid at higher dose should be avoided for 2 days before, on the day of, and 2 days following PEMINJO  
administration (see section 4.4).  
In the absence of data regarding potential interaction between PEMINJO and NSAIDs with longer half-  
lives, such as piroxicam or rofecoxib all patients taking these NSAIDs should interrupt dosing for at  
least 5 days before, on the day of, and at least 2 days after PEMINJO  
administration (see section 4.4). If concomitant administration of NSAIDs is necessary,  
patients should be monitored closely for toxicity, especially myelosuppression and gastrointestinal  
toxicity.  
Acetylsalicylic acid administered in low to moderate doses (325 mg orally every 6 hours) does not affect  
the pharmacokinetics of pemetrexed.  
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Product proprietary name: PEMINJO 100/500 INJ  
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The pharmacokinetics of pemetrexed are not influenced by concurrently administered cisplatin or  
carboplatin. Similarly, the pharmacokinetics of total platinum are unaltered by PEMINJO. Oral folic acid  
and intramuscular vitamin B12 supplementation do not affect the pharmacokinetics of pemetrexed.  
Pemetrexed undergoes limited hepatic metabolism. Results from in vitro studies with human liver  
microsomes indicated that pemetrexed would not be predicted to cause clinically significant inhibition  
of the metabolic clearance of medicines metabolised by CYP3A, CYP2D6, CYP2C9, and CYP1A2.  
Due to the increased thrombotic risk in patients with cancer, the use of anticoagulation treatment is  
frequent. The high intra-individual variability of the coagulation status during diseases and the possibility  
of interaction between oral anticoagulants and anti-cancer chemotherapy require increased frequency  
of INR (international normalised ratio) monitoring, if it is decided to treat the patient with  
oral anticoagulants.  
Concomitant use with yellow fever vaccine is contraindicated as there is a risk of fatal generalised  
vaccinale disease (see section 4.3)  
Concomitant use of live attenuated vaccines is not recommended (except yellow fever, for which  
concomitant use is contraindicated) as there is a risk of systemic, possibly fatal, disease. The risk is  
increased in patients who are already immunosuppressed by their underlying disease. Use an  
inactivated vaccine where it exists (poliomyelitis) (see section 4.4).  
4.6 Fertility, Pregnancy and lactation  
Women of childbearing potential / Contraception in males and females  
Women of childbearing potential must use effective contraception during treatment with PEMINJO and  
for 6 months after completion of treatment. PEMINJO can have genetically damaging effects. Sexually  
mature males are advised not to father a child during the treatment and up to 6 months thereafter.  
Contraceptive measures or abstinence are recommended (see section 4.4).  
Pregnancy  
There are no data on the use of PEMINJO in pregnant women, Animal studies have shown  
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reproductive toxicity such as birth defects and other defects on the development of the foetus, the  
course of gestation and peri- and post-development. The potential risk for humans is unknown.  
PEMINJO should be avoided during pregnancy due to the potential hazard to the foetus. Women should  
also be advised to avoid becoming pregnant while being treated with PEMINJO.  
Breastfeeding  
It is not known whether PEMINJO is excreted in human milk. Breastfeeding must be discontinued during  
PEMINJO therapy (see section 4.3)  
Fertility  
Due to the possibility of PEMINJO causing irreversible infertility, men are advised to seek counselling  
on sperm storage before starting PEMINJO treatment.  
4.7 Effects on ability to drive and use machine  
No studies on the effects on the ability to drive and use machines have been performed. However,  
PEMINJO may cause fatigue. Therefore, patients should be cautioned against driving a  
vehicle or operating machines if this event occurs.  
4.8 Undesirable effects  
a. Summary of the safety profile  
The most commonly reported undesirable effects related to pemetrexed, whether used as monotherapy  
or in combination, are bone marrow suppression manifested as anaemia, neutropenia, leukopenia,  
thrombocytopenia; and gastrointestinal toxicities, manifested as anorexia, nausea, vomiting, diarrhoea,  
constipation, pharyngitis, mucositis, and stomatitis. Other undesirable effects  
include renal toxicities, increased aminotransferases, alopecia, fatigue, dehydration, rash,  
infection/sepsis and neuropathy. Rarely seen events include Stevens-Johnson syndrome and toxic  
epidermal necrolysis.  
b. Tabulated summary of adverse reactions  
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Infections and Infestations  
Frequent:  
Blood and lymphatic system disorders  
Frequent: decreased: neutrophils / granulocytes, leukocytes, haemoglobin, platelets;  
febrile neutropenia  
Metabolism and nutrition disorders  
Frequent: dehydration  
Nervous system disorders  
Infection  
Frequent:  
Neuropathy- Sensory, taste disturbance  
Eye Disorders  
Frequent:  
Conjunctivitis  
Cardiac disorders  
Less frequent:  
Myocardial infarction, dysrhythmias  
Gastrointestinal disorders  
Frequent:  
Nausea, vomiting, mucositis/ stomatitis/ pharyngitis, anorexia, diarrhoea,  
constipation, dyspepsia/ heartburn, diarrhoea without colostomy,  
Elevation ALT (SGPT), AST (SGOT)  
Hepatobiliary disorders  
Frequent:  
Skin and subcutaneous tissue disorders  
Frequent:  
Rash/ desquamation, alopecia, pruritus  
Renal and urinary disorders  
Frequent:  
Serum creatinine elevation, creatinine clearance decreased, Renal disorders  
General disorders and administration site conditions  
Frequent  
Frequent: Fatigue, pain, edema, fever  
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of  
the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine.  
Health care providers are asked to report any suspected adverse to report any suspected  
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adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found  
online under SAHPRA’s publications: https://www.sahpra.org.za/publications/Index/8  
or to the Holder of certificate of registration through the mail: pvg.cdma@heterogroups.com  
4.9 Overdose  
Reported symptoms of overdose include neutropenia, anaemia, thrombocytopenia, mucositis, sensory  
polyneuropathy and rash. Anticipated complications of overdose include bone marrow suppression as  
manifested by neutropenia, thrombocytopenia and anaemia. In addition, infection with or without fever,  
diarrhoea and/or mucositis may be seen. In the event of suspected overdose, patients should be  
monitored with blood counts and should receive supportive therapy as necessary. The use of leucovorin  
in the management of PEMINJO overdose should be considered.  
5 PHARMACOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
Category and class: A26 Cytostatic agents  
Pharmacotherapeutic group: Folic acid analogues, ATC code: L01BA04  
Pemetrexed is a multitarget anticancer antifolate medicine that exerts its action by disrupting crucial  
folate-dependent metabolic processes essential for cell replication.  
In vitro studies have shown that pemetrexed behaves as a multitarget antifolate by inhibiting thymidylate  
synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase  
(GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and  
purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and  
membrane folate binding protein transport systems. Once in the cell, pemetrexed is rapidly and  
efficiently converted to polyglutamate forms by the enzyme folyl polyglutamate synthase. The  
polyglutamate forms are retained in cells and are even more potent inhibitors of TS and GARFT.  
Polyglutamation is a time- and concentration-dependent process that occurs in tumour cells and, to a  
lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life  
resulting in prolonged drug action in malignant cells.  
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5.2 Pharmacokinetic properties  
Pemetrexed has a steady-state volume of distribution of 16,1 litres. In vitro studies indicate that  
pemetrexed is approximately 81 % bound to plasma proteins. Binding was not notably affected by  
varying degrees of renal impairment. Pemetrexed undergoes limited hepatic metabolism.  
Pemetrexed is primarily eliminated in the urine, with 70 % to 90 % of the administered dose being  
recovered unchanged in urine within the first 24 hours following administration. Pemetrexed total  
systemic clearance is 91,8 ml/min and the elimination half-life from plasma is 3,5 hours in patients  
with normal renal function (creatinine clearance of 90 ml/min). Between-patient variability in clearance  
is moderate at 19,3 %. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration  
increase proportionally with dose. The pharmacokinetics of pemetrexed are consistent  
over multiple treatment cycles. The pharmacokinetic properties of pemetrexed are not influenced by  
concurrently administered cisplatin. Oral folic acid and Intramuscular vitamin B12 supplementation do  
not affect the pharmacokinetics of pemetrexed.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
Mannitol  
Sodium hydroxide  
Hydrochloric Acid  
6.2 Incompatibilities  
PEMINJO should ONLY be reconstituted and diluted with 0,9% sodium Chloride Injection, without  
preservative. (See preparation instructions above). PEMINJO is compatible with standard polyvinyl  
chloride administration sets and intravenous solution bags. PEMINJO is  
physically incompatible with lactated Ringer’s Injection and Ringer’s Injection.  
Co-administration of PEMINJO with other drugs and diluents has not been studied and therefore is not  
recommended.  
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6.3 Shelf life  
24 months for un-reconstituted solution  
For the reconstituted or diluted solution, chemical and physical in-use stability has been demonstrated  
for 24 hours at 25 °C. From a microbiological point of view PEMINJO should be used immediately. If  
not used immediately, in-use storage times and conditions prior to use are the  
responsibility of the user and would normally not be longer than 24 hours at 2 – 8 °C, unless  
reconstitution or dilution has taken place in controlled and validated aseptic conditions.  
6.4 Special precautions for storage  
Store at or below 25 °C.  
Keep the vial in the outer carton until required for use.  
KEEP OUT OF REACH OF CHILDREN.  
For storage conditions after reconstitution of the PEMINJO, (see section 6.3 Shelf-life).  
6.5 Nature and contents of container  
PEMINJO 100 INJ: 10 mL type I, clear, tubular glass vial, sealed with a 20 mm Lyo rubber stopper and  
20 mm purple coloured aluminium flip-off seal with matte top finish, packed in an outer carton.  
PEMINJO 500 INJ: 50 mL type I, clear, tubular glass vial, sealed with a 20 mm Lyo rubber stopper and  
20 mm purple coloured aluminium flip-off seal with matte top finish, packed in an outer carton.  
Pack size: 1 vial or 20 vials packed in a cardboard outer carton box.  
Not all pack sizes may be marketed.  
6.6 Special precautions for disposal and other handling  
1.Use aseptic technique during the reconstitution and further dilution of PEMINJO for intravenous  
infusion administration.  
2. Calculate the dose and the number of PEMINJO vials needed. Each vial contains an excess of  
PEMINJO to facilitate delivery of label amount.  
Initial: …K.B……….  
01 May 2024  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
3. Reconstitute each PEMINJO 100 INJ vial with 4,2 ml of sodium chloride 9 mg/ml (0.9%) solution for  
injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed. Gently swirl  
each vial until the powder is completely dissolved. The resulting solution is clear, nearly colourless and  
free from visible particles PEMINJO 500 INJ,  
Reconstitute each PEMINJO 500 INJ vial with 20 mL of sodium chloride 9 mg/ml (0,9 %) solution for  
injection, without preservative, resulting in a solution containing 25 mg/ml pemetrexed. Gently swirl  
each vial until the powder is completely dissolved. The resulting solution is clear, nearly colourless and  
free from visible particles.  
Further dilution is required  
4. The appropriate volume of PEMINJO solution must be further diluted to 100 mL with sodium chloride  
9 mg/ml (0,9 %), without preservative, and administered as an intravenous infusion over 10 minutes.  
5. PEMINJO prepared as directed above are compatible with polyvinyl chloride and polyolefin lined  
administration sets and infusion bags.  
6. PEMINJO must be inspected visually for particulate matter and discolouration prior to administration.  
If discolouration or particulate matter is observed, do not administer.  
7. PEMINJO solutions are for single use only. Any unused PEMINJO or waste material must be  
disposed of in accordance with local requirements.  
Preparation and administration precautions:  
Care should be exercised in the handling and preparation of PEMINJO. The use of gloves is  
recommended. If PEMINJO contacts the skin, wash the skin immediately and thoroughly with soap and  
water. If PEMINJO contacts the mucous membranes, flush thoroughly with  
water. PEMINJO is not a vesicant. There is not a specific antidote for extravasation of PEMINJO. There  
have been few reported cases of pemetrexed extravasation, which were not assessed as serious by  
the investigator. Extravasation should be managed by local standard practice as with other non-  
vesicants.  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
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01 May 2024  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: PEMINJO 100/500 INJ  
Dosage form and strength: Powder for solution for infusion and 100 mg/500 mg  
Name and address of the Holder of Certificate of Registration  
Hetero Drugs South Africa (Pty) Ltd.,  
Waterfall Corporate Campus  
Building No. 2, First floor,  
74 Waterfall Drive  
Midrand, 2066  
Telephone: 012 644 2120  
Fax number: 012 644 1564  
e-mail address: nokuthula.n@heterodrugs.com  
8 REGISTRATION NUMBER(S)  
PEMINJO 100 INJ: 56/26/0434.  
PEMINJO 500 INJ: 56/26/0435.  
9 DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION  
06 February 2024.  
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