Use
of Pemetrexed in a Patient With COVID-19
COVID-19
is an infectious respiratory disease caused by SARS-CoV-2, previously
referred to as "2019 novel coronavirus."1
Lilly
has not studied the use of pemetrexed in patients with COVID-19.
Clinicians
should use their clinical judgment in determining the most
appropriate approach in treating a patient with pemetrexed who has
confirmed or suspected COVID-19.
Potential
Risk and Benefit Considerations
Clinical
Use
Treating
physicians should assess the patient’s individual benefit/risk
ratio considering the patient's signs and symptoms, prior medical
history, concomitant medications, and other individual factors when
making pemetrexed treatment decisions in the context of COVID-19.
Adverse reactions of pemetrexed to be considered in particular, in
the context of COVID-19, include
myelosuppression
interstitial
pneumonitis, and
increased
risk of toxicity with ibuprofen in patients with renal impairment
(see below for further information).2
Pemetrexed
dose adjustments, made at the physician’s discretion, should
follow the label. Supportive treatment should be provided as
clinically indicated and patients monitored appropriately.3
Myelosuppression-Related
Warnings and Precautions
Pemetrexed
can cause severe myelosuppression (as manifested by neutropenia,
thrombocytopenia, and anemia or pancytopenia) resulting in a
requirement for transfusions and which may lead to neutropenic
infection. The risk of myelosuppression is increased in patients who
do not receive vitamin supplementation. Patients treated with
pemetrexed must be instructed to take folic acid and vitamin B12
with pemetrexed as a prophylactic measure to reduce treatment-related
toxicity.2
Interstitial
Pneumonitis-Related Warnings and Precautions
Serious
interstitial pneumonitis, including fatal cases, can occur with
pemetrexed treatment2.
Treatment should be withheld for acute onset of new or progressive
unexplained pulmonary symptoms such as dyspnoea, cough, or fever
pending diagnostic evaluation. If pneumonitis is confirmed,
pemetrexed should be permanently discontinued.3
Potential
Drug-Drug Interaction With Ibuprofen
Ibuprofen
decreases the clearance of pemetrexed and increases its exposure
(AUC). Patients with mild to moderate renal impairment (CrCl 45-79
mL/min)
have
increased risk of pemetrexed toxicity, and
should
avoid administration of ibuprofen for 2 days before, the day of, and
2 days following administration of pemetrexed.2
Monitor
patients more frequently for myelosuppression, renal, and GI toxicity
if concomitant administration of ibuprofen cannot be avoided.2
Aspirin,
administered in low to moderate doses (325 mg every 6 hours), does
not affect the pharmacokinetics of pemetrexed.3
Additional
Consideration From Clinical Trial Experience
Dyspnoea
and cough are common adverse reactions (incidence ≥20%) of
pemetrexed when administered in combination with pembrolizumab and
platinum chemotherapy.3
Infectious
Disease Resources for COVID-19
For
the most current information regarding COVID-19, please refer to the
following resources:
References
1.
Naming the coronavirus disease (COVID-19) and the virus that causes
it. World Health Organization. Accessed March 17, 2020.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it
2.
Alimta [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands
3.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4.
Coronavirus disease (COVID-19) outbreak. World Health Organization
Europe. Accessed March 20, 2020.
http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov
5.
COVID-19. European Centre for Disease Prevention and Control.
Accessed March 20, 2020.
https://www.ecdc.europa.eu/en/novel-coronavirus-china
6.
European Society for Medical Oncology. Accessed March 23th.
https://www.esmo.org/newsroom/covid-19-and-cancer/covid-19-useful-resources
7.
[NICE] National Institute for Health and Care Excellence.
Coronavirus (COVID-19). Available from:
https://www.nice.org.uk/covid-19.
Accessed 25 March 2020.
Glossary
AUC
= area under the curve
COVID-19
= coronavirus disease 2019
CrCl
= creatinine clearance
ECDC
= European Centre for Disease Prevention and Control
ESMO
= European Society for Medical Oncology
EU
WHO = World Health Organization (European regional office)
GI =
gastrointestinal
Lilly
= Eli Lilly and Company
SARS-CoV-2
= severe acute respiratory syndrome coronavirus 2