pemetrexed (Rx)

Brand and Other Names:Alimta
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution reconstituted, intravenous

  • 100mg/vial
  • 500mg/vial

Malignant Pleural Mesothelioma

Indicated for mesothelioma in combination with cisplatin in patients whose disease is unresectable or who are not candidates for curative surgery

In combination with cisplatin: 500 mg/m² IV on Day 1 of each 21-day cycle  

Continue until disease progression or unacceptable toxicity

Nonsquamous Non-Small Cell Lung Carcinoma

Initial treatment

  • In combination with pembrolizumab and platinum chemotherapy
    • Indicated for initial treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations
    • 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
  • In combination with cisplatin
    • Indicated for initial treatment of patients with locally advanced or metastatic nonsquamous NSCLC
    • 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  

Second-line treatment for recurrent or metastatic disease

  • Indicated as a single agent for treatment of patients with recurrent, metastatic nonsquamous NSCLC after prior chemotherapy
  • 500 mg/m² IV on Day 1 of each 21-day cycle  
  • Continue until disease progression or unacceptable toxicity

Maintenance treatment

  • 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 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

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Interactions

Interaction Checker

and pemetrexed

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            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

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            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
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            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, intravenous 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

            • Therapy can cause fetal harm when administered to a pregnant woman; because of potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment for at least 6 months after final dose
            • Advise males with female partners of reproductive potential to 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.

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            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%)

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            Administration

            IV Incompatibilities

            Solution: Do not use calcium-containing solutions for reconstitution, including Lactated Ringer or Ringer solution

            Coadministration not recommended

            IV Compatibilities

            Solution: 0.9% NaCl

            IV Preparation

            Pemetrexed a cytotoxic drug; follow applicable special handling and disposal procedures

            Reconstitute with 0.9% NaCl (preservative-free); add 4.2 mL to 100-mg vial and 20 mL to the 500-mg vial to achieve a concentration of 25 mg/mL

            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 pemetrexed from vial(s) and discard vial with any unused portion

            Further dilute reconstituted vial with 0.9% NaCl (preservative-free) 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

            Unused vials: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Reconstituted vials: Refrigerate 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 2-8°C (36-46°F) for no more than 24 hr from the time of reconstitution; discard after 24 hr

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.