Alimta500 mg/vial

Alimta is a chemotherapy agent (antifolate) used, always under the supervision of a physician experienced in cancer chemotherapy, for the following FDA-approved and guideline-supported indications:

Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

• First-line combination therapy (established): In combination with pembrolizumab and platinum chemotherapy, as initial treatment of metastatic non-squamous NSCLC in patients with no EGFR or ALK genomic tumor aberrations.
• First-line combination therapy (established): In combination with cisplatin, for initial treatment of locally advanced or metastatic non-squamous NSCLC.
• Maintenance therapy (established): As a single agent, for maintenance treatment of metastatic non-squamous NSCLC in patients whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
• Second-line/recurrent disease (established): As a single agent, for the treatment of recurrent metastatic non-squamous NSCLC after prior chemotherapy.

Alimta is not indicated, and should not be used, for the treatment of squamous cell NSCLC (adjunct/combination use only in non-squamous histology).

Malignant Pleural Mesothelioma

• Combination therapy (established): In combination with cisplatin, for the treatment of patients with unresectable malignant pleural mesothelioma.

Alimta is used only in combination regimens for first-line NSCLC and mesothelioma treatment, and as single-agent therapy only for maintenance or previously-treated recurrent non-squamous NSCLC, as outlined above. It is not appropriate for self-directed or non-oncology use.

Each vial of Pemetrexed for injection contains Pemetrexed disodium, equivalent to Pemetrexed base, as a sterile lyophilized powder (or sterile concentrated solution, depending on the manufacturer's formulation) intended for intravenous infusion after reconstitution and dilution. Common vial strengths include 100 mg and 500 mg of Pemetrexed (as the free acid equivalent). No other active pharmaceutical ingredients are included; formulations may contain inactive excipients such as mannitol and agents for pH adjustment.

Alimta is a multitargeted antifolate antineoplastic (anticancer) agent administered by intravenous infusion in a hospital or specialized oncology setting. It belongs to the antimetabolite class of chemotherapy drugs and works by interfering with folate-dependent enzymes that cancer cells require to synthesize DNA and RNA, thereby halting rapid tumor cell replication.

Alimta is used mainly for certain types of non-small cell lung cancer (non-squamous histology) and malignant pleural mesothelioma, typically combined with a platinum-based chemotherapy agent (such as cisplatin) or, in specific settings, with immunotherapy. Because it is a cytotoxic agent with a narrow therapeutic margin, Alimta must only be prescribed, dosed, and administered by, or under the direct supervision of, a physician experienced in the use of cancer chemotherapeutic agents, with mandatory vitamin supplementation and laboratory monitoring as described below.

Alimta belongs to the antineoplastic (anticancer) agents class, specifically the antimetabolite / multitargeted antifolate subclass of chemotherapy drugs.

Pemetrexed is a multitargeted antifolate that disrupts folate-dependent metabolic processes essential for cell replication. After transport into cells and conversion to polyglutamate forms (which are retained longer in cells and are more potent inhibitors), Pemetrexed inhibits several key folate-dependent enzymes:

• Thymidylate synthase (TS): the primary target, essential for synthesis of thymidine, a building block of DNA.
• Dihydrofolate reductase (DHFR).
• Glycinamide ribonucleotide formyltransferase (GARFT), involved in purine synthesis.

By blocking these enzymes, Pemetrexed depletes the intracellular pools of thymidine and purine nucleotides needed for DNA and RNA synthesis and repair, leading to inhibition of cell proliferation and, ultimately, cell death in rapidly dividing cells such as tumor cells (as well as some normal rapidly dividing cells, which accounts for its characteristic toxicities). Pemetrexed is administered intravenously, is highly protein bound in plasma, undergoes minimal hepatic metabolism, and is primarily eliminated unchanged by renal excretion, which is why renal function is critical to its safe dosing.

Alimta is for intravenous infusion only and must be prepared and given by trained healthcare personnel in an oncology setting:

• The reconstituted and diluted solution is administered as an IV infusion over 10 minutes.
• Alimta must not be mixed with, or administered simultaneously through the same line as, calcium-containing diluents (e.g., Lactated Ringer's solution) unless the line is flushed appropriately.
• Cisplatin (when used in combination) is typically administered approximately 30 minutes after the end of the Alimta infusion, per the specific regimen.
• Do not administer if the reconstituted/diluted solution is discolored or contains particulate matter.
• Use appropriate cytotoxic drug handling and disposal precautions (gloves, eye protection, and safe-handling procedures) during preparation and administration.

Only well-established, clinically significant interactions with Alimta are listed below:

• NSAIDs (e.g., ibuprofen) and other nephrotoxic drugs: Concurrent use may reduce renal clearance of Alimta, increasing plasma levels and the risk of serious toxicity (myelosuppression, GI toxicity, renal impairment). In patients with mild-to-moderate renal impairment (creatinine clearance 45–79 mL/min), short-acting NSAIDs should be avoided for 2 days before, on the day of, and 2 days after Alimta administration; caution and closer monitoring are advised even with normal renal function.
• Nephrotoxic agents (e.g., aminoglycosides, certain contrast agents): May further reduce Alimta clearance and increase toxicity risk; use with caution and monitor renal function closely.
• Live vaccines: As with other chemotherapy agents, live or live-attenuated vaccines should generally be avoided during Alimta treatment due to the risk of disseminated infection from immunosuppression.
• Other myelosuppressive or nephrotoxic chemotherapy agents: Combination may increase the risk of additive toxicity; dose and monitoring adjustments are managed by the treating oncologist.

Always inform the treating physician of all medicines, supplements, and over-the-counter drugs (especially any NSAID/pain reliever) being used before and during Alimta therapy.

Alimta commonly causes side effects related to its effect on rapidly dividing cells; severity and pattern vary by whether it is given alone or in combination with cisplatin or pembrolizumab-platinum regimens.

Very Common / Common

• Fatigue, decreased appetite (anorexia)
• Nausea, vomiting, constipation, diarrhea
• Stomatitis/mucositis, mouth sores
• Myelosuppression: neutropenia, anemia, thrombocytopenia (increasing risk of infection, bleeding, or need for transfusion)
• Elevated liver enzymes (transaminases)
• Rash or skin reactions (reduced by corticosteroid premedication)
• Alopecia (hair thinning/loss, less common than with many other chemotherapy agents)

Serious / Less Common

• Severe myelosuppression with febrile neutropenia or serious infection
• Renal impairment or acute kidney injury (see Precautions)
• Interstitial pneumonitis (lung inflammation) — may present as new or worsening cough, shortness of breath, or fever
• Severe bullous, blistering, or exfoliative skin reactions
• Radiation recall reaction in patients with prior radiotherapy
• Severe gastrointestinal toxicity (dehydration from vomiting/diarrhea)

Patients should promptly report fever, unusual bleeding or bruising, severe mouth sores, breathing difficulty, or severe skin reactions to their treating physician.

Pregnancy: Alimta can cause fetal harm and is a cytotoxic agent with demonstrated embryo-fetal toxicity in animal studies. Alimta should be strictly avoided during pregnancy; it is used in pregnancy only if there is no alternative and only if the physician determines the potential benefit clearly justifies the potential risk to the fetus, and pregnancy should be excluded before starting treatment in patients of reproductive potential. Women of reproductive potential should use effective contraception during treatment and for at least 6 months after the final dose; men with female partners of reproductive potential should use effective contraception during treatment and for at least 3 months after the final dose.

Breastfeeding: Because of the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during Alimta treatment and for a period after the final dose, as advised by the treating physician. Always consult a physician before considering breastfeeding around the time of Alimta therapy.

Alimta must be administered only under the supervision of a physician experienced in the use of cancer chemotherapeutic agents, with the following precautions strictly observed:

• Mandatory vitamin supplementation: Folic acid and vitamin B12 supplementation (see Dosage and Administration) must be started before treatment and continued as directed to reduce the risk of severe hematologic and gastrointestinal toxicity; do not omit this supplementation.
• Renal function monitoring: Creatinine clearance must be assessed before every cycle. Alimta should be withheld in patients with creatinine clearance below 45 mL/min, as reduced renal clearance significantly increases toxicity risk (see Interaction section regarding NSAIDs).
• Bone marrow suppression: Complete blood counts must be monitored before each dose; doses are withheld or reduced for significant neutropenia, thrombocytopenia, or anemia.
• Corticosteroid premedication: Required to reduce the incidence and severity of skin rash (see Dosage and Administration).
• Interstitial pneumonitis: Monitor for new or worsening respiratory symptoms; discontinue if severe pneumonitis is diagnosed.
• Severe skin reactions: Discontinue permanently if severe bullous, blistering, or exfoliative skin reactions occur.
• Third-space fluid collections (e.g., pleural effusion, ascites): May require drainage before Alimta administration, as significant third-space fluid may alter drug clearance and increase toxicity.
• Not for squamous NSCLC: Alimta is not indicated, and evidence does not support its use, in squamous cell NSCLC.

Alimta must be handled and disposed of according to institutional cytotoxic drug procedures.

There is no established specific antidote for Alimta overdose. Symptoms of overdose are generally an exaggeration of known side effects, particularly severe myelosuppression (neutropenia, thrombocytopenia, anemia), mucositis, and skin rash. If an overdose of Alimta is suspected, seek immediate medical attention or contact emergency services/poison control right away. Management is supportive, in a hospital setting, and includes close monitoring of blood counts and renal/hepatic function, leucovorin (folinic acid) rescue as directed by the treating physician, and treatment of complications such as infection, bleeding, or dehydration as they arise. Do not attempt home treatment for a suspected overdose.

Store unopened Alimta vials at room temperature (below 25°C), protected from light, in their original packaging, and keep out of reach of children. After reconstitution and dilution for infusion, the prepared solution should be stored under refrigeration (2–8°C) and used within the timeframe specified by the product labeling (typically within 24 hours); do not freeze the reconstituted solution unless the specific product labeling states otherwise. All preparation and storage of Alimta solutions must follow the hospital pharmacy's cytotoxic-drug handling protocols.

Renal Impairment

Alimta is primarily eliminated by the kidneys. Alimta should be withheld in patients with creatinine clearance below 45 mL/min due to significantly increased risk of severe toxicity; use in patients with any degree of renal impairment requires close monitoring (see Precautions and Warnings).

Hepatic Impairment

Data in patients with significant hepatic impairment are limited; use with caution and close monitoring of liver function and toxicity if hepatic impairment is present.

Elderly Patients

Elderly patients may be at increased risk of certain toxicities (e.g., myelosuppression, fatigue); no specific dose adjustment based on age alone is established, but closer clinical monitoring is advised.

Pediatric Patients

Safety and efficacy of Alimta in pediatric patients have not been established; Alimta is not recommended for use in children.

Third-Space Fluid Accumulation

Patients with clinically significant pleural effusion or ascites may need this fluid drained prior to Alimta administration, as it may prolong drug exposure and increase toxicity.

The duration of Alimta treatment is determined by the treating oncologist based on the specific regimen, response, and tolerability:

• In combination with cisplatin (with or without pembrolizumab) for first-line non-squamous NSCLC or mesothelioma, treatment is typically continued for up to 4–6 cycles (each cycle = 21 days), or until disease progression or unacceptable toxicity, per the specific protocol.
• As single-agent maintenance therapy after first-line chemotherapy, or in combination regimens continuing beyond the initial cycles, Alimta (with or without pembrolizumab) is generally continued until disease progression or unacceptable toxicity occurs.

Do not stop, extend, or alter the treatment schedule without the treating physician's guidance, as premature discontinuation or missed monitoring can affect both safety and treatment outcomes.

Alimta for injection is supplied as a sterile powder that must be reconstituted before use, following the specific product's package insert:

• Reconstitute each vial with preservative-free 0.9% Sodium Chloride Injection (normal saline) to the volume specified on the product labeling, gently swirling until fully dissolved (do not shake vigorously).
• The resulting reconstituted solution is further diluted in 0.9% Sodium Chloride Injection to a final infusion volume (commonly around 100 mL) as specified by the manufacturer's instructions.
• Inspect the reconstituted and diluted solution visually for particulate matter and discoloration before administration; do not use if either is observed.
• Alimta must not be reconstituted or diluted with calcium-containing diluents, including Lactated Ringer's solution.
• Use appropriate aseptic technique and cytotoxic drug handling precautions throughout reconstitution, dilution, and administration.

Antineoplastic agents; Antimetabolites; Multitargeted antifolates.

Pemetrexed is a multitargeted antifolate that enters cells via folate transport systems and is converted intracellularly into polyglutamate forms. These forms inhibit multiple folate-dependent enzymes essential for nucleotide synthesis: primarily thymidylate synthase (TS), and also dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). By blocking these enzymes, Pemetrexed depletes the cellular supply of thymidine and purine nucleotides required for DNA and RNA synthesis, disrupting cell replication and repair, and leading to selective cytotoxic effects on rapidly dividing malignant cells.

D

The safety and efficacy of Alimta in pediatric patients have not been established. Alimta is approved for use in adult patients with specific types of non-small cell lung cancer and malignant pleural mesothelioma, and clinical trial data supporting a defined pediatric dose or indication are not available. Alimta should not be used in children outside of a formal clinical trial setting, and any such use should only occur under the direct guidance of a pediatric oncology specialist.