In February 2004 United States Food and Drug Administration
(FDA) approved Pemetrexed for treating Malignant Pleural Mesothelioma
(MPM) in combination with cisplatin, which is a chemotherapeutic
drug that contains platinum. Combination of Pemetrexed with
cisplatin is the first and only drug that FDA has approved for
MPM treatment when it is not possible to perform surgery.
FDA approved the drug in July 2004 to be used as a second line
agent for treating metastatic or advanced Non-Small Cell Lung
Cancer (NSCLC).
The drug is also used as a single agent or in combination with
other chemotherapy drugs to treat different types of cancers,
including bladder cancer, colorectal carcinoma, breast cancer,
and cervical cancer.
Pemetrexed is developed and marketed the Indianapolis-based
company, Eli Lilly and Company.
Pemetrexed Availability
Alimta, the name of the drug with which Pemetrexed is marketed,
is supplied in the form of a sterile lyophilized powder that
is meant for intravenous infusion. Color of Almita is white
to either light yellow or green-yellow lyophilized solid. The
drug is available in single-dose 100 mg or 500 mg vials.
-
100 mg vial contains pemetrexed disodium
that is equivalent to 100 mg pemetrexed and 106 mg mannitol.
-
500 mg vial contains pemetrexed disodium
that is equivalent to 500 mg pemetrexed and 500 mg mannitol.
To adjust the pH value Hydrochloric acid and (or) Sodium Hydroxide
may be added to the medicine.
Important Safety Considerations
Myelosuppression is usually the dose-limiting toxicity with
pemetrexed therapy.
Contraindication
Pemetrexed is contraindicated in patients who have a history of
severe hypersensitivity reaction to pemetrexed or to any other
ingredient used in the formulation.
Warnings
Patients must be instructed to take folic acid and vitamin B12
with Pemetrexed as a prophylaxis to reduce treatment-related hematologic
and GI toxicity.
Pemetrexed should not be administered to patients
with a creatinine clearance <45 mL/min. One patient with severe
renal impairment (creatinine clearance 19 mL/min) who did not
receive folic acid and vitamin B12 died of drug-related toxicity
following administration of Pemetrexed alone.
Pemetrexed can suppress bone marrow function, as
manifested by neutropenia, thrombocytopenia, and anemia.
Pregnancy Category D—Pemetrexed may cause fetal
harm when administered to a pregnant woman.
Precautions
Complete blood cell counts, including platelet counts and periodic
chemistry tests, should be performed on all patients receiving
Pemetrexed.
Patients should not begin a new cycle of treatment
unless the ANC is ≥ 1500 cells/mm3 and the platelet count is ≥
100,000 cells/mm3.
Pretreatment with dexamethasone or its equivalent
has been reported to reduce the incidence and severity of skin
rash.
The effect of third space fluid, such as pleural
effusion and ascites, on pemetrexed is unknown.
In patients with clinically significant third space
fluid, consideration should be given to draining the effusion
prior to pemetrexed administration.
Caution should be used when administering ibuprofen
concurrently with Pemetrexed to patients with mild to moderate
renal insufficiency (creatinine clearance from 45 to 79 ml/min).
Patients with mild to moderate renal insufficiency should avoid
taking NSAIDs with short elimination half-lives for a period for
2 days before, the day of, and 2 days following administration
of pemetrexed. In the absence of data regarding potential interaction
between pemetrexed and NSAIDs with longer half-lives, all patients
taking these NSAIDs should interrupt dosing for at least 5 days
before, the day of, and 2 days following pemetrexed administration.
If concomitant administration of an NSAID is necessary, patients
should be monitored closely for toxicity, especially myelosuppression,
renal and gastrointestinal toxicity.
Concomitant administration of nephrotoxic drugs
or substances that are tubularly secreted could result in delayed
clearance of pemetrexed.
It is recommended that nursing be discontinued if
the mother is being treated with pemetrexed.
Pemetrexed should be administered under the supervision
of a qualified physician experienced in the use of antineoplastic
agents.
Dose adjustments may be necessary in patients with
hepatic insufficiency.
Dosing and Modification Guidelines
Complete blood cell counts, including platelet
counts and periodic chemistry tests, should be performed on all
patients receiving pemetrexed.
Patients should not begin a new cycle of treatment
unless the ANC is ≥ 1500 cells/mm3 and the platelet count is ≥
100,000 cells/mm3.
Dose adjustments at the start of a subsequent cycle
should be based on nadir hematologic counts or maximum nonhematologic
toxicity from the preceding cycle of therapy. Modify or suspend
therapy according to the Dosage Reduction Guidelines in the full
Prescribing Information.
Pemetrexed has shown safety advantages over docetaxel
The effect of Pemetrexed on survival is reasonably likely based
on response rate.*
Patients receiving Pemetrexed experienced lower
rates of:
Patients receiving Pemetrexed experienced a significant
increase in ALT.
* In the second line NSCLC setting, docetaxel has
demonstrated overall survival compared with the best supportive
care. Controlled trials demonstrating survival benefit of Pemetrexed
are still ongoing.
Source: http://www.lillyoncology.com/professionals/Pemetrexed_nsclc_safety_info.jsp?reqNavId=1.6.3 |
Pemetexed
What Is Pemetrexed?