Pexate 100/Pexate 500

Pexate 100/Pexate 500

pemetrexed

Manufacturer:

Naprod

Distributor:

Multicare

Marketer:

Multicare
Full Prescribing Info
Contents
Pemetrexed disodium.
Description
Each vial contains: Pemetrexed (as disodium heptahydrate) 100 mg and 500 mg, respectively.
Pemetrexed for injection is lyophilized powder for intravenous infusion. Pemetrexed disodium heptahydrate has the chemical name L-Glutamic acid, N-[4-{2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl}-benzoyl}-, disodium salt heptahydrate. It is a white to almost-white solid with molecular formula of C20H19N5Na2O6•7H2O and a molecular weight of 597.49.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Pemetrexed is a multi-targeted anti-cancer antifolate agent 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 multi-targeted 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 polyglutame forms by the enzyme folylpolyglutamate 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 tumor cells ad, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Pharmacokinetics: The pharmacokinetic properties of Pemetrexed following single-agent administration have been evaluated in 426 cancer patients with a variety of solid tumors at doses ranging from 0.2 to 838 mg/m2 infused over a 10-minute period. Pemetrexed has a steady-state volume of distribution of 9 L/m2. 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 the urine within the first 24 hours following administration. Pemetrexed total systemic clearance 1s 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.
Indications/Uses
Malignant Pleural Mesothelioma: Pemetrexed in combination with cisplatin is indicated for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.
Non-Small Cell Lung Cancer: Pemetrexed in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Pemetrexed is indicated as monotherapy for the maintenance treatment of progressed immediately following platinum-based chemotherapy (see Pharmacology: Pharmacodynamics under Actions).
Pemetrexed is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
Dosage/Direction for Use
Pemetrexed should only be administered under the supervision of a physician qualified in the use of anti-cancer chemotherapy. The Pemetrexed solution must be prepared according to the instructions provided in Cautions for Usage.
Malignant Pleural Mesothelioma: In Patients treated for malignant pleural mesothelioma, the recommended dose of pemetrexed is 500 mg/m2 of 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/m2 BSA infused over two hours approximately 30 minutes after completion of the Pemetrexed infusion on the first day of each 21-day cycle. Patients must receive adequate anti-emetic treatment and appropriate hydration prior to and/or after receiving cisplatin.
Non-Small Cell Lung Cancer: Single Agent Use: In patients treated for non-small cell lung cancer, the recommended dose of Pemetrexed is  500 mg/m2 BSA administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.
Combination Use with Cisplatin: The recommended dose of Pemetrexed is 500 mg/m2 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/m2 BSA infused 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 Pemetrexed administration. The corticosteroid should be equivalent to 4 mg of dexamethasone administered orally twice a day (see Precautions). To reduce toxicity, patients treated with Pemetrexed should also receive vitamin supplementation (see Precautions). Patients must take oral folic acid or a multivitamin containing folic acid (350 to 1000 micrograms) on a daily basis. At least five doses of folic acid must be taken during the seven days preceding the first dose of intramuscular injection of vitamin B12 (1000 micrograms) in the week preceding the first dose of Pemetrexed and once every three cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as Pemetrexed.
Monitoring: Patients receiving Pemetrexed should be monitored before each dose with a complete blood count, including a differential white cell count (WCC) and platelet count. Prior to each chemotherapy, administration blood chemistry tests should be collected to evaluate renal and hepatic function. Before the start of any cycle of chemotherapy, patients are required to have the following: Absolute Neutrophil Count (ANC) should be ≥1,500 cells/mm3 and platelets should be ≥100,000 cells/mm3. Creatinine clearance should be ≥45 mL/min. The total bilirubin should be ≤1.5 times upper limit of normal. Alkaline phosphatase (AP), aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) should be ≤3 times upper limit of normal. Alkaline phosphatase, AST and ALT ≤5 times upper limit of normal is acceptable if liver has tumor involvement.
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 should be re-treated using the guidelines in Tables 1, 2, and 3, which are applicable for PEMETREXED used as a single agent or in combination with cisplatin. See Table 1.

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If patients develop non-haematologic toxicities ≥grade 3 (excluding neurotoxicity), PEMETREXED 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.

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In the event of neurotoxicity, the recommended dose adjustment for PEMETREXED and cisplatin is documented in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is observed.

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Treatment with PEMETREXED should be discontinued if a patient experiences any haematologic or non-haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.
Elderly: 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: There is no relevant use of PEMETREXED in the paediatric population in malignant pleural mesothelioma and non-small cell lung cancer.
Patients with renal impairment (standard Cockcroft and Gault formula or Glomerular Filtration Rate measured Tc99m DPTA serum clearance method).
Pemetrexed is primarily eliminated unchanged by renal excretion. In clinical studies, patients with creatinine clearance of ≥45 mL/min required no dose adjustments other than those recommended for all patients. There are insufficient data on the use of pemetrexed in patients with creatinine clearance below 45 mL/min; therefore, the use of pemetrexed is not recommended (see Precaution).
Patients with 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 aminotransferase >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.
Overdosage
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 anemia. 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 calcium folinate/folinic acid in the management of Pemetrexed overdose should be considered.
Contraindications
Pemetrexed is contraindicated in patients with known hypersensitivity to Pemetrexed or to any of the excipients. Breastfeeding must be discontinued during Pemetrexed therapy (see Use in Pregnancy & Lactation). Concomitant yellow fever vaccine (see Interactions).
Special Precautions
Pemetrexed can suppress bone marrow function as manifested by neutropenia, thrombocytopenia and anaemia (or pancytopenia) (see Adverse Reactions).
Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy and Pemetrexed should not be given to patients until absolute neutrophil count (ANC) returns to ≥1,500 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 Dosage & Administration).
Less toxicity ad reduction in Grade 3/4 haematologic and non-haematologic 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, patients treated with Pemetrexed must be instructed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related toxicity (see Dosage & Administration).
Skin reactions have been reported in patients not pre-treated with a corticosteroid. Pretreatment with dexamethasone (or equivalent) can reduce the incidence and severity of skin reactions (see Dosage & Administration).
An insufficient numbers of patients have been studied with creatinine clearance of below 45 mL/min. Therefore, the use of Pemetrexed in patients with creatinine clearance of <45 mL/min is not recommended (see Dosage & Administration).
Patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min) should avoid taking non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen, and acetylsalicylic acid (>1.3 g daily) for 2 days prior to, on the day of, and at least 2 days after administration of Pemetrexed (see Interactions). Patients with mild to moderate renal insufficiency eligible for Pemetrexed 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 Pemetrexed administration (see Interactions).
The effect of third space fluid, such as pleural effusion or ascites, on Pemetrexed was not fully defined. A phase 2 study of Pemetrexed in 31 solid tumor patients with stable third space fluid demonstrated no difference in Pemetrexed dose normalized plasma concentration or clearance compared to patients without third space fluid collections. Thus, drainage of third space fluid collection prior to Pemetrexed treatment should be considered, but may not be necessary.
Due to the gastrointestinal toxicity of Pemetrexed given in combination with cisplatin, severe dehydration has 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 and cerebrovascular events have been uncommonly reported during clinical studies with Pemetrexed, usually when given in combination with another cytotoxic agent. Most of the patients in whom these events have been observed had preexisting cardiovascular risk factors (see Adverse Reactions).
Immunodepressed status is common in cancer patients. As a result, concomitant use of live attenuated vaccines (except yellow fever) is not recommended (see Interactions).
Pemetrexed 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. Owing to the possibility of Pemetrexed treatment causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment. Women of childbearing potential must use effective contraception during treatment with Pemetrexed (see Use in Pregnancy & Lactation).
Effects on Ability to Drive and Use Machines: 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.
Use In Pregnancy & Lactation
There are no data from the use of Pemetrexed in pregnant women but Pemetrexed like other anti-metabolites is suspected to cause serious birth defects when administered during pregnancy. Animal studies have shown reproductive toxicity (see Pharmacology under Actions).
Pemetrexed should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and the risk for foetus (see Precautions).
Women of childbearing potential must use effective contraception during treatment with Pemetrexed. Pemetrexed 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. Owing to the possibility of Pemetrexed treatment causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment.
It is not known whether Pemetrexed is excreted in human milk and adverse effects on the suckling child cannot be excluded. Breast-feeding must be discontinued during Pemetrexed (see Contraindications).
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Adverse Reactions
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, diarrhea, 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.
Table 4 provides the frequency and severity of undesirable effects that have been reported in >5% of 168 patients with mesothelioma who were randomised to receive cisplatin and Pemetrexed and 163 patients with mesothelioma randomised to receive single agent cisplatin. In both treatment arms, these chemonaive patients were fully supplemented with folic acid and vitamin B12 (see Table 4).
Very common ≥10%; common is normally defined as >1% and <10%. For the purpose of Table 4, cut off of 5% was used for inclusion of all events where the reporter considered a possible relationship to Pemetrexed ad cisplatin. Clinically relevant CTC toxicities that were reported in ≥1% and ≤5% (common) of the patients that were randomly assigned to receive cisplatin and Pemetrexed include: Increased AST, ALT, and GGT, infection, pyrexia, febrile neutropenia, renal failure, chest pain, and urticaria. Clinically relevant CTC toxicities that were reported in 1% (uncommon) of the patients that were randomly assigned to receive cisplatin and Pemetrexed include arrhythmia and motor neuropathy. See Table 4.

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Table 5 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 B12 supplementation and 276 patients randomly assigned to receive single agent docetaxel. All patients were diagnosed with locally advanced or metastatic non-small cell lung cancer and received prior chemotherapy. See Table 5.
Very common ≥10%; common is normally defined as >1% and <10. For the purpose of Table 5, a cut off 5% was used for the inclusion of all events where the reporter considered a possible relationship to Pemetrexed.
Clinically relevant CTC toxicities that were reported in >1% and <5% (common) of the patients that were randomly assigned to Pemetrexed include: Sensory neuropathy, abdominal pain, increased creatinine febrile neutropenia, infection without neutropenia, allergic reaction/hypersensitivity and erythema multiforme.
Clinically relevant CTC toxicities that were 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 previously described, 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 both chemonaive and heavily pre-treated breast patients with pre-existing liver metastases and/or abnormal liver function tests.

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Table 6 provides the frequency and severity of undesirable effects considered possibly related to study drug that have been reported in >5% of 839 patients with NSCLC who were randomized to study and received cisplatin and Pemetrexed and 830 patients with NSCLC who were randomized 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 B12 (see Table 6).
Very common ≥10%, common is normally defined as >1% and <10%. For the purpose Table 6, 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 was reported in ≥1% and ≤5% (common) of the patients that were randomly assigned to receive cisplatin and Pemetrexed include: AST increase, ALT increase, infection, febrile neutropenia, renal failure, pyrexia, dehydration, conjunctivitis and creatinine clearance decreases.
Clinically relevant toxicity that was reported in <1% (uncommon) of the patients that were randomly assigned to receive cisplatin and Pemetrexed include: GGT increase, chest pain, arrhythmia, and motor neuropathy.

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Table 7 provides the frequency and severity of undesirable effects considered possibly related to study drug that have been reported in >5% of 800 patients randomly assigned to receive single agent Pemetrexed ad 402 patients randomly assigned to receive placebo in the single agent Pemetrexed maintenance (JMEN:N=663) and continuation Pemetrexed maintenance (PARAMOUNT:N=663) and continuation Pemetrexed maintenance (PARAMOUNT:N=539) studies. All patients were diagnosed with stage IIIB of IV NSCLC and had received prior platinum-based chemotherapy.
Patients in both study arms were fully supplemented with folic acid and vitamin B12 (see Table 7).

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Clinically relevant CTC toxicity of any grade that was reported in ≥1% and ≤5% of the patients that were randomly assigned to Pemetrexed include: Febrile neutropenia, infection, decreased platelets, decreased creatinine clearance, diarrhoea, constipation, edema, alopecia, increased creatinine, pruritus/itching, fever (in the absence of neutropenia), ocular surface disease (including conjunctivitis), increased lacrimation, decreased glomerular filtration rate, dizziness and motor neuropathy.
Clinically relevant CTC toxicity that was reported in <1% (uncommon) of the patients that were randomly assigned to Pemetrexed include: Allergic reaction/hypersensitivity, erythema multiforme, renal failure, supraventricular arrhythmia and pulmonary embolism.
Safety was assessed for patients who were randomised to receive Pemetrexed (N=800). The incidence of adverse reactions was evaluated for patients who received ≤6 cycles of Pemetrexed maintenance (N=568), and compared to patients who received >6 cycles of Pemetrexed (N=232). Increases in adverse reactions (all grades) were observed with longer exposure; however, no statistically significant differences in any individual Grade 3/4/5 adverse reactions were seen.
Serious cardiovascular and cerebrovascular events, including myocardial infarction, angina pectoris, cerebrovascular accident and transient ischaemic attack have been uncommonly reported during clinical studies with Pemetrexed, usually when given in combination with another cytotoxic agent.
Most of the patients in whom these events have been observed had pre-existing cardiovascular risk factors.
Rare cases of hepatitis, potentially serious, have been reported during clinical studies with Pemetrexed. Pancytopenia has been uncommonly reported during clinical trials with Pemetrexed.
Additional Clinical Trial Data: In clinical trials, sepsis which in some cases was fatal occurred in approximately 1% of patients.
Cases of esophagitis have been reported uncommonly in clinical trials with Pemetrexed.
During post-marketing surveillance, the following adverse reactions have been reported in patients treated with Pemetrexed.
Gastrointestinal: Rare cases of colitis have been reported in patients treated with Pemetrexed.
General Disorders and Administration Site Conditions: Uncommon cases of edema have been reported in patients treated with Pemetrexed.
Injury, Poisoning and Procedural Complications: Rare cases of radiation recall have been reported in patients who have previously received radiotherapy.
Respiratory: Rare cases of interstitial pneumonitis have been reported in patients treated with Pemetrexed.
Skin: Rare cases of bullous conditions have been reported including Stevens-Johnson syndrome and Toxic epidermal necrolysis which in some cases were fatal.
Cases of peripheral ischemia leading sometimes to extremity necrosis have been reported.
Drug Interactions
Pemetrexed is primarily eliminated unchanged by tubular secretion and to a lesser extent by glomerular filtration. In vitro studies indicate that Pemetrexed is actively secreted by OAT3 (organic anion transporter 3). Concomitant administration of nephrotoxic drugs (e.g. aminoglycoside, loop diuretics, platinum compounds, cyclosporin) could result in delayed clearance of Pemetrexed. This combination should be used with caution. If necessary, creatinine clearance should be closely monitored.
Concomitant administration of substances that are also tubularly secreted (e.g. probenecid, penicillin) could potentially result in delayed clearance of Pemetrexed. Caution should be made when these drugs are combined with Pemetrexed. If necessary, creatinine clearance should be closely monitored.
In patients with normal renal function (creatinine clearance ≥80 mL/min), high doses of non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen >1,600 mg/day) and aspirin at higher dosage (≥1.3 g daily) may decrease Pemetrexed elimination and, consequently, increase the occurrence of Pemetrexed to patients with normal function (creatinine clearance ≥80 mL/min). In patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min), the concomitant administration of Pemetrexed with NSAIDs (e.g. ibuprofen) or aspirin at higher dosage should be avoided for 2 days before, on the day of, and 2 days following Pemetrexed administration (see Precautions).
In the absence of data regarding potential interaction between Pemetrexed and NSAIDs with longer half-lives as piroxicam or rofecoxib in patients with mild to moderate renal insufficiency, patients with mild to moderate renal insufficiency taking these NSAIDs should interrupt dosing for at least 5 days before, o the day of, and at least 2 days after Pemetrexed administration (see Precautions). 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 drugs metabolised by CYP3A, CYP2D6, CYP2D9 and CYP1A2.
Interactions Common to All Cytotoxics: Due to the increased thrombotic risk in patients with cancer, the use of coagulation treatment is frequent. The high intraindividual variability of the coagulation status during diseases and the possibility of interaction between oral anticoagulants and anticancer chemotherapy require increased frequency of INR (International Normalised Ratio) monitoring, if it is decided to treat the patient with oral anticoagulant.
Concomitant Use Contraindicated: Yellow fever vaccine. Risk of fatal generalised vaccinale disease (see Contraindications).
Concomitant Use Not Recommended: Live attenuated vaccines (except yellow fever). Risk of systemic, possibly fatal, disease. The risk is increased in subjects who are already immunosuppressed by their underlying disease. Use an inactivated vaccine where it exists (poliomyelitis) (see Precautions).
Caution For Usage
Instructions for Use and Handling: Use appropriate aseptic technique during the reconstitution and further dilution of Pemetrexed for intravenous infusion administration.
Calculate the dose and number of Pemetrexed vials needed. The vial contains and excess of Pemetrexed to facilitate delivery of the label amount.
Reconstitute 100 mg vials 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. Reconstitute 500 mg vials 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 and ranges in color from colorless to yellow or green-yellow without adversely affecting product quality. The pH of the reconstituted solution is between 6.6 to 7.8. Further dilution is required.
The appropriate volume of reconstituted Pemetrexed solution should be further diluted to 100 mL with sodium chloride 9 mg/mL (0.9%) solution for injection, without preservatives and administered as an intravenous infusion over 10 minutes.
Pemetrexed infusion solutions prepared as previously directed are compatible with polyvinyl chloride and polyolefin-lined administration sets and infusion bags.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.
Pemetrexed solutions are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
Chemical and physical stability at refrigerated or ambient room temperature and lighting. When prepared as directed, reconstitution and infusion solutions of Pemetrexed for injection contain no antimicrobial preservative. Discard any unused portion. Reconstitution and further dilution prior to intravenous infusion is only recommended with 0.9% Sodium Chloride Injection.
Preparation and Administration Precautions: As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of Pemetrexed infusion solutions. The use of gloves is recommended. If a Pemetrexed solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If Pemetrexed solutions contact the mucous membranes, flush thoroughly with water. Pemetrexed is not a vesicant. There is not a specific antidote for extravasation of Pemetrexed. 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.
Incompatibilities: Pemetrexed is physically incompatible with diluents containing calcium, including lactated Ringer's Injection and Ringer's Injection. In the absence of compatibility studies (with other drugs and diluents), this medicinal product must not be mixed with other medicinal products.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
Storage after reconstitution: After reconstitution, store the product in a refrigerator (2°C-8°C) and use within 24 hours.
MIMS Class
Cytotoxic Chemotherapy
ATC Classification
L01BA04 - pemetrexed ; Belongs to the class of antimetabolites, folic acid analogues. Used in the treatment of cancer.
Presentation/Packing
Pexate 100: Soln for IV infusion (lyo) (vial) 100 mg x 1's.
Pexate 500: Soln for IV infusion (lyo) (vial) 500 mg x 1's.
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