Pemetrexed

427.41

427.41

04Q9AIZ7NO

698037

DTXSID2048329

C61614

Crystals from 50% methanol/methylene chloride

L01BA04|L - Antineoplastic and immunomodulating agents

2933990090

187

0.2

1.6±0.1 g/cm3

1.724

6X10-21 mm Hg at 25 deg C at 25 deg C /Estimated/

Henry's Law constant: 2.08X10-29 atm-cu m/mole at 25 °C /Estimated/

pKa1 = 3.6; pKa2 = 4.4 (carboxylic moieties) /Estimated/

White to almost white solid. /Disodium salt/|Hydroxy radical reaction rate constant = 2.4X10-10 cu cm/molec-sec at 25 °C /Estimated/

3

P201, P202, P260, P264, P270, P273, P280, P281, P301+P312, P302+P352, P305+P351+P338, P308+P313, P314, P321, P330, P332+P313, P337+P313, P362, P405, P501

H302

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl pemetrexed disodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pemetrexed Disodium/

|Danger|H302 (94.2%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501|Aggregated GHS information provided by 69 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

If a solution of pemetrexed contacts the skin, wash the skin immediately and thoroughly with soap and water. If pemetrexed contacts the mucous membranes, flush thoroughly with water.

Pemetrexed therapy is associated with a low-to-moderate rate of serum enzyme elevations, but these are generally mild, transient and without accompanying symptoms or jaundice. Serum ALT or AST elevations above 5 times ULN occur in 1% to 6% of patients, but are usually self-limited in course and rarely require dose modification or discontinuation. No instances of clinically apparent acute liver injury attributed to pemetrexed have been reported. In addition, pemetrexed has not been linked to sinusoidal obstruction syndrome or to reactivation of hepatitis B, but it is rarely used in high doses in neoplastic disease or in conditioning regimens for bone marrow transplantation, situations in which other neoplastic agents are commonly associated with these complications.

Coadministration of nephrotoxic drugs could result in delayed clearance of pemetrexed. Coadministration of substances that also are tubularly secreted (e.g., probenecid) could potentially result in delayed clearance of pemetrexed.|Exercise caution when administering pemetrexed concurrently with nonsteroidal anti-inflammatory drugs (NSAIDs) to patients whose Ccr is less than 80 mL/min.|Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.|Results from in vitro studies with human liver microsomes predict that pemetrexed would not cause clinically significant inhibition of metabolic clearance of drugs metabolized by CYP3A, CYP2D6, CYP2C9, and CYP1A2. No studies were conducted to determine the cytochrome P450 isozyme induction potential of pemetrexed, because ALIMTA used as recommended (once every 21 days) would not be expected to cause any significant enzyme induction.|For more Interactions (Complete) data for PEMETREXED (9 total), please visit the HSDB record page.

81%

Pemetrexed's production and use as an antineoplastic drug(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 22,000(SRC), determined from a structure estimation method(2), indicates that pemetrexed is expected to be immobile in soil(SRC). The pKa values for the two carboxylic acid moieties of pemetrexed are 3.6 and 4.4(3), indicating that this compound will primarily exist as an anion and anions do not volatilize from moist soil surfaces(4). Pemetrexed is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-21 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 22,000(SRC), determined from a structure estimation method(2), indicates that pemetrexed is expected to adsorb to suspended solids and sediment(SRC). The estimated pKa values for the two carboxylic acid moieties of pemetrexed are 3.6 and 4.4(3). These pKa values indicate that pemetrexed will exist almost entirely in the anionic form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(4), an estimated BCF of 3.2(SRC), from an estimated log Kow of 0.16(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pemetrexed, which has an estimated vapor pressure of 6X10-21 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase pemetrexed may be removed from the air by wet and dry deposition(SRC). Since it may absorb UV light at wavelengths > 290 nm, pemetrexed may be susceptible to direct photolysis from sunlight; however, the rate of this reaction is not known(SRC).

Pemetrexed is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Since it may absorb UV light at wavelengths >290 nm, pemetrexed may be susceptible to direct photolysis from sunlight; however, the rate of this reaction is not known(SRC).

An estimated BCF of 3.2 was calculated for pemetrexed(SRC), using an estimated log Kow of 0.16(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC), provided the compound is not altered physically or chemically once released into the environment(SRP).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for pemetrexed can be estimated to be 22,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that pemetrexed is expected to be immobile in soil. The pKa values of pemetrexed are 3.6 and 4.4(3), indicating that this compound will exist in the dissociated form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

The pKa values for the two carboxylic acid moieties of pemetrexed are 3.6 and 4.4(1), indicating that this compound will primarily exist as an anion and anions do not volatilize from water or moist soil surfaces. Pemetrexed is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-21 mm Hg(SRC), determined from a fragment constant method(2).

Occupational exposure to pemetrexed may occur through inhalation and dermal contact with this compound at workplaces where pemetrexed is produced or used. Exposure to the drug among the general population may be limited to those being administered pemetrexed (an antineoplastic). (SRC)

Used in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy|FDA Label|Malignant pleural mesotheliomaPemetrexed in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed 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 locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.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.|Malignant pleural mesotheliomaPemetrexed Hospira in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Hospira 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 Hospira is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed Hospira 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.|Malignant pleural mesotheliomaPemetrexed Krka in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Krka 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 Krka is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed Krka 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.|Malignant pleural mesothelioma Pemetrexed medac in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancer Pemetrexed medac 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 medac is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed medac 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.|Malignant pleural mesotheliomaPemetrexed Fresenius Kabi in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Fresenius Kabi 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 Fresenius Kabi is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. Pemetrexed Fresenius Kabi 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.|Malignant pleural mesotheliomaPemetrexed Accord in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Accord 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 Accord is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed Accord 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.|Malignant pleural mesotheliomaPemetrexed Hospira UK Limited in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Hospira UK Limited 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 (see SmPC section 5.1).Pemetrexed Hospira UK Limited is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy (see SmPC section 5.1).Pemetrexed Hospira UK Limited 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 (see SmPC section 5.1).|Malignant pleural mesotheliomaCiambra in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerCiambra 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.Ciambra is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Ciambra 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.|Malignant pleural mesotheliomaPemetrexed Sandoz in combination with cisplatin is indicated for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Sandoz 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 Sandoz is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed Sandoz 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.|Malignant pleural mesotheliomaAlimta in combination with cisplatin is indicated for the treatment of chemotherapy-naïve patients with unresectable malignant pleural mesothelioma.Non-small-cell lung cancerAlimta 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.Alimta is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Alimta 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.|Malignant pleural mesotheliomaPemetrexed Lilly in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.Non-small cell lung cancerPemetrexed Lilly 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 Lilly is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.Pemetrexed Lilly 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.|Carcinoma of the head and neck (Covered by class waiver: oropharyngeal epithelial carcinoma, excluding nasopharyngeal carcinoma), Malignant pleural mesothelioma|Drug: Pemetrexeddisodium

Pemetrexed is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.

Antineoplastic Agents

Antineoplastic|Malignant pleural mesothelioma: In combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.|Carcinoma, lung, non-small cell (treatment)-Pemetrexed is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy.

Pemetrexed can suppress bone marrow function manifested by neutropenia, thrombocytopenia, and anemia; myelosuppression is usually the dose-limiting toxicity. ...|Instruct patients treated with pemetrexed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related hematologic and GI toxicity. In clinical studies, less overall toxicity and reductions in grade 3/4 hematologic and nonhematologic toxicity such as neutropenia, febrile neutropenia, and infection with grade 3/4 neutropenia were reported when pretreatment with folic acid and vitamin B12 was administered. ...|FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./|Advise patients to avoid becoming pregnant. If pemetrexed is used during pregnancy or if the patient becomes pregnant while taking pemetrexed, apprise the patient of the potential hazard to the fetus.|For more Drug Warnings (Complete) data for PEMETREXED (13 total), please visit the HSDB record page.

Preclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Folic Acid Antagonists.)|Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)

Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration.|16.1 L|91.8 mL/min [Cancer patients with normal renal function receiving 0.2 to 838 mg/m2 infusion over a 10-minute period]|Pemetrexed ... is primarily eliminated in the urine ... within the first 24 hours following administration.|The total systemic clearance of pemetrexed is 91.8 mL per min in patients with normal renal function (creatinine clearance of 90 mL per min). The clearance decreases, and exposure (AUC) increases, as renal function decreases. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration (Cmax) increase proportionally with dose.|The pharmacokinetics of pemetrexed administered as a single agent in doses ranging from 0.2 to 838 mg/sq m infused over a 10 minute period have been evaluated in 426 cancer patients with a variety of solid tumors. Pemetrexed AUC and Cmax increase proportionally with dose. The pharmacokinetics of pemetrexed do not change over multiple treatment cycles. Pemetrexed has a steady-state volume of distribution of 16.1 L. In vitro studies indicate that pemetrexed is approximately 81% bound to plasma proteins. Binding is not affected by degree of renal impairment.|Time to ANC nadir with pemetrexed systemic exposure (AUC), varied between 8 to 9.6 days over a range of exposures from 38.3 to 316.8 ug per hr per mL. Return to baseline ANC occurred 4.2 to 7.5 days after the nadir over the same range of exposures.|For more Absorption, Distribution and Excretion (Complete) data for PEMETREXED (7 total), please visit the HSDB record page.

Metabolized by Cytochrome P450 Enzymes|Pemetrexed is not metabolised to an appreciable extent and ... 70% to 90% of the dose recovered unchanged ...

3.5 hours|... The elimination half life of pemetrexed is 3.5 hours in patients with normal renal function (Ccr90 mL/min).

Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in 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 converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor 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.|Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in 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 converted to polyglutamate forms by the enzyme folyl polyglutamate synthase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor 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.|... Activity of the /pemetrexed/ may be partially preserved under conditions in which cells are highly resistant to other thymidylate synthase inhibitors, possibly because of premetrexed's secondary inhibitory effects on purine synthesis. ... Pemetrexed activity is modulated by natural folates within cells that compete for polyglutamation at the level of folylpolyglutamate synthetase. Cells resistant to methotrexate because of impaired transport via the reduced folate carrier may retain partial sensitivity to pemetrexed. This is due to concurrent diminished transport of physiologic reduced folates and contraction of the cellular folate pool, thereby relaxing the usual level of suppression of pemetrexed polyglutamation. The risk of pemetrexed toxicity is increased when cellular folates are suboptimal.

If an overdose occurs, general supportive measures should be instituted as deemed necessary. ... In clinical trials, leucovorin was permitted for CTC grade 4 leukopenia lasting >/= 3 days, CTC grade 4 neutropenia lasting ./= 3 days, and immediately for CTC grade 4 throbocytopenia, bleeding associated with grade 3 thrombocytopenia, or grade 3 or 4 mucositis.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/HUMAN EXPOSURE STUDIES/ FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./|/SIGNS AND SYMPTOMS/ There have been few cases of pemetrexed overdose. Reported toxicities include neutropenia, anemia, thrombocytopenia, mucositis, and rash. Anticipated complications of overdose include bone marrow suppression as manifested by neutropenia, thrombocytopenia, and anemia. In addition, injection with or without fever, diarrhea, and mucositis may be seen.|Advise patients to avoid becoming pregnant. If pemetrexed is used during pregnancy or if the patient becomes pregnant while taking pemetrexed, apprise the patient of the potential hazard to the fetus.

231,514, LY

Alimta (Eli Lilly); powder for injection, lyophilized: 500 mg; 500 mg mannitol. In single-use vials.

Multitargeted antifolate; inhibits thymidylate synthase as well as other folate dependent enzymes.|Information available in 2005 indicated that Pemetrexed disodium was used in the manufacture of pharmaceutical preparations in the following countries: United States (1,2)

Human drugs -> Armisarte (previously Pemetrexed Actavis) -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Pemetrexed Hospira -> EMA Drug Category|Human drugs -> Pemetrexed Krka -> EMA Drug Category|Human drugs -> Pemetrexed medac -> EMA Drug Category|Antineoplastic agents, Folic acid analogues -> Human pharmacotherapeutic group|Human drugs -> Pemetrexed Fresenius Kabi -> EMA Drug Category|Human drugs -> Pemetrexed Accord -> EMA Drug Category|Human drugs -> Pemetrexed Pfizer (previously known as Pemetrexed Hospira UK Limited) -> EMA Drug Category|ANTIMETABOLITES, Folic acid analogues -> Human pharmacotherapeutic group|Human drugs -> Ciambra -> EMA Drug Category|Human drugs -> Pemetrexed Sandoz -> EMA Drug Category|Human drugs -> Alimta -> EMA Drug Category|Human drugs -> Pemetrexed Lilly -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients