Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 100mg/vial (Alimta)
- 500mg/vial (Alimta)
injectable solution
- 500mg/vial (Pemfexy)
Mesothelioma
Indicated as initial treatment, in combination with cisplatin, for malignant pleural mesothelioma in patients whose disease is unresectable or are not candidates for curative surgery
In combination with cisplatin: Pemetrexed 500 mg/m2 IV on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity
Nonsquamous Non-Small Cell Lung Carcinoma
Combination with pembrolizumab and platinum chemotherapy
- Alimta only
- Indicated for initial treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations
- In combination with pembrolizumab and platinum chemotherapy: Pemetrexed 500 mg/m2 IV on Day 1 of each 21-day cycle for 4 cycles
- Following completion of platinum-based therapy, continue pemetrexed with or without pembrolizumab until disease progression or unacceptable toxicity
Combination with cisplatin
- Alimta, Pemfexy
- Indicated for initial treatment of patients with locally advanced or metastatic nonsquamous NSCLC
- In combination with cisplatin: Pemetrexed 500 mg/m2 IV on Day 1 of each 21-day cycle for up to 6 cycles in the absence of disease progression or unacceptable toxicity
Single agent
- Alimta, Pemfexy
- Indicated as a single agent for treatment of patients with recurrent, metastatic nonsquamous NSCLC after prior chemotherapy
- Also, indicated as a single agent for maintenance treatment of patients with locally advanced or metastatic, nonsquamous NSCLC whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy
- 500 mg/m2 IV on Day 1 of each 21-day cycle
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
Modification of ibuprofen dosing in patients on pemetrexed with CrCl (45-79 mL/min)
- Avoid ibuprofen for 2 days before, day of, and 2 days following administration of therapy
- Closely monitor for myelosuppression, renal toxicity, and gastrointestinal toxicity, if concomitant use of ibuprofen cannot be avoided
Delay initiation of the next cycle of pemetrexed until:
- Recovery of nonhematologic toxicity Grade ≤2; AND
- Absolute neutrophil count (ANC) ≥1500 cells/mm3 AND
- Platelet count ≥100,000 cells/mm3
Adjust to 75% of previous dose
- ANC <500/mm3 and platelets ≥50,000 cells/mm3
- Platelet count <50,000 cells/mm3 without bleeding
- Any Grade 3 or 4 nonhematologic toxicities EXCEPT mucositis or neurologic toxicity
- Diarrhea requiring hospitalization
Adjust to 50% of previous dose
- Platelet count <50,000 cells/mm3 with bleeding
- Grade 3 or 4 mucositis
Discontinue
- Recurrent Grade 3 or 4 myelosuppression after 2 dose reductions
-
Permanently discontinue
- Grade 3 or 4 neurologic toxicity
- Recurrent Grade 3 or 4 nonhematologic toxicity after 2 dose reductions
- Severe and life-threatening skin toxicity
- Interstitial pneumonitis
Renal impairment
- CrCl (calculated by Cockcroft-Gault equation) ≥45 mL/min: No dosage adjustment necessary
- CrCl <45 mL/min: No recommended dose; do not administer
Hepatic impairment
- Not studied; no effect of elevated AST, ALT, or total bilirubin on the pharmacokinetics of pemetrexed was observed in clinical studies
Dosing Considerations
Limitation of use: Not indicated for treatment of patients with squamous cell NSCLC
Obtain complete blood cell (CBC) count on Days 1, 8, and 15 of each cycle; assess CrCl prior to each cycle
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10% (All Grades)
Nausea (31-82%)
Vomiting (16-57%)
Neutropenia (11-56%)
Fatigue (34-48%)
Anemia (19-26%)
Thrombocytopenia (8-23%)
Stomatitis/pharyngitis (15-23%)
Anorexia (20-22%)
Diarrhea (13-17%)
Rash (14-16%)
Decreased CrCl (16%)
Constipation (6-12%)
Alopecia (11%)
Elevated creatinine (11%)
>10% (Grade 3 or 4)
Neutropenia (5-23%)
Nausea (12%)
Vomiting (2-11%)
1-10% (All Grades)
Sensory neuropathy (10%)
Taste disturbance (8%)
Increased ALT (1-8%)
Fever (8%)
Pruritus (7%)
Increased AST (1-7%)
Dehydration (7%)
Alopecia (6%)
Dyspepsia (5%)
Conjunctivitis (5%)
Abdominal pain (1-5%)
Allergic reaction/hypersensitivity (1-5%)
Febrile neutropenia (1-5%)
Infection (1-5%)
Urticaria (1-5%)
Chest pain (1-5%)
Erythema multiforme (1-5%)
Renal failure (1-5%)
Motor or sensory neuropathy (1-5%)
Dyspepsia (1%)
1-10% (Grade 3 or 4)
Fatigue (5-10%)
Thrombocytopenia (2-5%)
Anemia (4%)
Dehydration (4%)
Diarrhea (4%)
Nausea (3%)
Stomatitis/pharyngitis (1-3%)
Increased ALT (2%)
Anorexia (2%)
Rash (1%)
Alopecia (1%)
Constipation (1%)
Anorexia (1%)
Increased AST (1%)
Decreased CrCl (1%)
<1%
Supraventricular arrhythmias
Renal failure
Motor neuropathy
Postmarketing Reports
Gastrointestinal: Colitis, pancreatitis
Blood and lymphatic system: Immune-mediated hemolytic anemia
General: Edema
Injury, poisoning, and procedural complications: Radiation recall
Respiratory: Interstitial pneumonitis
Skin: Serious and fatal bullous skin conditions, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Warnings
Contraindications
History of severe hypersensitivity reaction to pemetrexed
Cautions
Severe myelosuppression may occur, resulting in a requirement for transfusions and which may lead to neutropenic infection; risk of myelosuppression is increased in patients who do not receive vitamin supplementation; initiate supplementation with oral folic acid and intramuscular vitamin B-12 prior to first dose of therapy; continue vitamin supplementation during treatment and for 21 days after last dose to reduce severity of hematologic and gastrointestinal toxicity
Therapy can cause severe, and sometimes fatal, renal toxicity
Serious and sometimes fatal, bullous, blistering, and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, can occur; permanently discontinue for severe and life-threatening bullous, blistering or exfoliating skin toxicity
Serious interstitial pneumonitis can occur with treatment; withhold therapy for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation; if pneumonitis confirmed, permanently discontinue therapy
Radiation recall can occur with treatment in patients who have received radiation weeks to years previously; monitor for inflammation or blistering in areas of previous radiation treatment; permanently discontinue therapy for signs of radiation recall
Based on findings from animal studies and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; avoid pregnancy (see Pregnancy)
Drug interactions overview
- Pemetrexed is a OAT3/OAT4 substrate; ibuprofen, an OAT3 inhibitor, inhibited the uptake of pemetrexed in OAT3-expressing cell cultures; data predict that at clinically relevant concentrations, other NSAIDs (naproxen, diclofenac, celecoxib) would not inhibit the uptake of pemetrexed
Pregnancy & Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman
There are no available data in pregnant women; in animal reproduction studies, IV administration of pemetrexed to pregnant mice during organogenesis was teratogenic, resulting in developmental delays and malformations at doses lower than recommended human dose of 500 mg/m2; advise pregnant women of the potential risk to a fetus
Contraception
- Females of reproductive potential: Use effective contraception during treatment for at least 6 months after final dose
- Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months after final dose
Infertility
- Therapy may impair fertility in males of reproductive potential; it is not known whether these effects on fertility are reversible
Lactation
There is no information regarding presence of drug or its metabolites in human milk, effects on breastfed infant, or on milk production; because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 week after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Antifolate antineoplastic agent
Disrupts folate-dependent metabolic processes essential for cell replication
Distribution
Vd (ss): 16.1 L
Protein bound: 81%
Metabolism
Metabolites: Polyglutamate forms
Enzymes inhibited
- Thymidylate synthase
- Dihydrofolate reductase
- Glycinamide ribonucleotide formyltransferase
- All folate-dependent enzymes involved in de novo biosynthesis of thymidine and purine nucleotides
Elimination
Total body clearance: 91.8 mL/min
Half-life: 3.5 hr
Excretion: Urine (70-90%)
Administration
IV Incompatibilities
Alimta
- Do not use calcium-containing solutions for reconstitution, including Lactated Ringer or Ringer solution
Pemfexy
- Do not use other diluents, such as Lactated Ringer or Ringer solution
IV Compatibilities
Alimta: 0.9% NaCl
Pemfexy: Dextrose 5%; compatible with polyolefin infusion bags with polyvinyl chloride (PVC) ports
IV Preparation
Pemetrexed a cytotoxic drug; follow applicable special handling and disposal procedures
Reconstitution
- Alimta: Reconstitute with 0.9% NaCl (preservative-free); add 4.2 mL to 100-mg vial and 20 mL to the 500-mg vial; final vial concentration is 25 mg/mL
Further dilution
- Gently swirl until completely dissolved; resulting solution is clear and ranges in color from colorless to yellow/green-yellow without adversely affecting quality
- Visually inspect particulate matter and discoloration prior to further dilution; if particulate matter is observed, discard vial
- Withdraw calculated dose from vial(s) and discard vial with any unused portion
- Further dilute reconstituted vial with 0.9% NaCl (Alimta) or Dextrose 5% (Pemfexy) to achieve a total volume of 100 mL for IV infusion
Premedication Regimen
Folic acid: 400-1000 mcg PO qDay beginning 7 days before first pemetrexed dose; continue until 21 days after last dose
Vitamin B-12: 1 mg IM beginning 1 week before first pemetrexed dose and repeat every 3 cycles thereafter; subsequent doses may be administered on the same day as pemetrexed
Do not substitute PO vitamin B-12 for IM (see Cautions)
Dexamethasone: 4 mg PO BID for 3 consecutive days starting the day before pemetrexed administration
IV Administration
Infuse over 10 min
For combination therapy: Administer after pembrolizumab and prior to carboplatin or cisplatin
Storage
Alimta
- Unused vials: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
- Reconstituted vials: Refrigerate at 2-8°C (36-46°F) for no longer than 24 hr from the time of reconstitution; discard vial after 24 hr
- Diluted infusion: Refrigerate at 2-8°C (36-46°F) for no more than 24 hr from the time of reconstitution; discard after 24 hr
Pemfexy
- Unused vials: Refrigerate at 2-8°C (36-46°F)
- Reconstituted vials: Refrigerate at 2-8°C (36-46°F) or ambient room temperature for no longer than 48 hr from the time of reconstitution; discard vial after 48 hr
- Diluted infusion: Refrigerate at 2-8°C (36-46°F) for no more than 48 hr from the time of reconstitution; discard after 48 hr
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Patient Handout
Formulary
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